2011 ASCO Annual Meeting

CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.

Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.

"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."

Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).

The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.

In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.

The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.

Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms’ tumor (3), and neuroblastoma (1).

The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.

Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.

Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."

Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.

Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.

"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.

CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.

Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.

"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."

Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).

The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.

In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.

The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.

Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms’ tumor (3), and neuroblastoma (1).

The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.

Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.

Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."

Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.

Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.

"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.

CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.

Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.

"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."

Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).

The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.

In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.

The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.

Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms’ tumor (3), and neuroblastoma (1).

The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.

Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.

Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."

Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.

Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.

"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.

CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.

Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.

"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."

Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).

The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.

In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease, and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.

The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development was 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.

Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms' tumor (3), and neuroblastoma (1).

The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.

Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.

Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."

Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.

Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.

"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.

CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.

Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.

"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."

Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).

The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.

In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease, and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.

The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development was 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.

Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms' tumor (3), and neuroblastoma (1).

The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.

Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.

Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."

Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.

Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.

"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.

CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.

Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.

"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."

Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).

The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.

In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease, and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.

The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development was 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.

Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms' tumor (3), and neuroblastoma (1).

The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.

Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.

Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."

Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.

Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.

"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.

CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.

Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.

"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."

Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).

The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.

In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.

The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.

Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms’ tumor (3), and neuroblastoma (1).

The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.

Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.

Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."

Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.

Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.

"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.

CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.

Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.

"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."

Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).

The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.

In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.

The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.

Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms’ tumor (3), and neuroblastoma (1).

The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.

Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.

Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."

Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.

Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.

"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.

CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.

Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.

"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."

Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).

The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.

In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.

The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.

Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms’ tumor (3), and neuroblastoma (1).

The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.

Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.

Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."

Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.

Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.

"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.

CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.

Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.

"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."

Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).

The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.

In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.

The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.

Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms’ tumor (3), and neuroblastoma (1).

The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.

Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.

Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."

Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.

Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.

"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.

CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.

Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.

"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."

Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).

The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.

In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.

The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.

Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms’ tumor (3), and neuroblastoma (1).

The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.

Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.

Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."

Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.

Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.

"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.

CHICAGO – Survivors of childhood cancer have a nearly threefold increased risk of melanoma, compared with the general population, according to an analysis of the Childhood Cancer Survivor Study.

Among 14,358 5-year survivors, the cumulative incidence of a subsequent melanoma was 0.52% at 35 years from their initial cancer. The standard incidence ratio for subsequent melanoma was 2.83 and excess absolute risk 0.11/1,000 person-years.

"Although the cumulative incidence is low, this is potentially a significant problem," lead author Dr. Alberto Pappo said at the annual meeting of the American Society of Clinical Oncology. "Our findings justify increased awareness and the need for improved adherence to recommended surveillance guidelines in childhood cancer survivors."

Dr. Pappo said the analysis was sparked by a report last year from the Childhood Cancer Survivor Study showing that 5-year survivors had an increased cumulative incidence of subsequent neoplasms (20.5%) as well as second malignant neoplasms (8%) (J. Natl. Cancer Inst. 2010 Jul 21;102:1083-95).

The 14,358 patients in the current analysis were diagnosed with childhood cancer between 1970 and 1986, and compared with participants in the Surveillance, Epidemiology, and End Results (SEER) database. Median follow-up was 24 years.

In all, 53 survivors developed 59 melanomas, said Dr. Pappo, director of the solid tumor division at St. Jude Children’s Research Hospital, Memphis. Among them, two patients had ocular melanoma, nine had in situ disease and two had other secondary malignancies before the diagnosis of melanoma. Five patients developed two or more melanomas, he pointed out.

The median age at the time of melanoma diagnosis was 32 years, and median time for tumor development 20.7 years. At the time of the analysis, 43 of the 53 patients (81%) were still alive. Four patients died of melanoma.

Among the 53 melanoma patients, primary diagnoses included acute lymphoblastic leukemia (15), lymphoma (14), bone/soft tissue (15), brain (5), Wilms’ tumor (3), and neuroblastoma (1).

The cumulative incidence of melanoma ranged from 0.29% for a primary diagnosis of brain cancer to 0.87% for survivors of soft tissue and bone sarcoma. The incidence was 0.43% for childhood leukemia and 0.55% for lymphoma.

Survivors who developed melanoma were significantly more likely to be more than 10 years old at the time of their initial cancer diagnosis (P less than .001) and to have a family history of cancer (P = .01). However, univariate analysis by age at diagnosis, sex, family history of cancer, treatment era, race, and alkylating score identified no significant risk factors, he said.

Attendees asked whether there is a cut point at which clinicians should pay particular attention to melanoma in this population. Dr. Pappo replied, "I am not sure if annual skin examinations are recommended for all childhood cancer survivors or just for those who receive radiotherapy, but perhaps for specific subsets, such as those with ALL or soft tissue sarcomas, that may be something worth implementing."

Dr. Pappo pointed out that the researchers are seeking more detailed tumor location and radiotherapy exposure data and that the study lacked data on factors known to contribute to melanoma such as sun exposure, number of nevi, and modifying genes.

Invited discussant Dr. Louise C. Strong, a professor of genetics at the University of Texas M.D. Anderson Cancer Center, Houston, called for further studies to elucidate the risk factors and genetics responsible for the increased incidence of melanoma observed in the study. She went on to say that studies in other populations at higher-risk for melanoma, such as transplant and immunosuppressed patients, have shown that prognosis for early stage I and II melanoma is the same as the general population but may actually be worse for late-stage disease.

"To me this is mostly a good news message because as long as we can educate our patients and can develop prevention and intervention programs, then it should work," she said.

The Childhood Cancer Survivor Study is funded by the National Cancer Institute. Dr. Pappo, his coauthors, and Dr. Strong reported no relevant conflicts of interest.

CHICAGO – That lenalidomide can improve overall and progression-free survival rates in multiple myeloma patients is evident, but whether the drug also increases their risk of second primary cancers is debatable.

Of three studies looking at the question, only one found an association between secondary primary malignancies and lenalidomide (Revlimid) in first-line therapy, investigators reported at the American Society of Clinical Oncology annual meeting.

And even then the risk was low – far less than the risk of death from multiple myeloma without a lenalidomide-containing regimen, said Dr. Antonio P. Palumbo of the University of Torino (Italy) and the Italian Multiple Myeloma Study Group.

Two other studies – one with 6-year follow-up data on continuous lenalidomide in first-line therapy and the other on lenalidomide in relapsed/refractory disease – failed to spot a signal for second cancer risk.

"I think it’s fair to say that currently we lack clear answers due to small numbers and study limitations," said Dr. C. Ola Landgren of the National Cancer Institute, the invited discussant for all three papers.

"I think we need to put both benefits and risks into the algorithms when we think about these things. ... I also think despite the fact that we don’t have clear data, we always have to discuss these things with our patients, and we as doctors have to stay updated as more information emerges," he said.

Three randomized clinical trials stirred the debate by reporting in separate presentations at the 2010 annual meeting of the American Society of Hematology that they saw more hematologic malignancies in lenalidomide treatment arms than in control groups (McCarthy, P.L. et al, abstract 37; Attal, M. et al, abstract 310; Palumbo, A. et al, abstract 622).

Despite these reports, 25 years after a multiple myeloma diagnosis, the cumulative incidence of all second cancers is about 8%, whereas the cumulative probability of death from competing causes is more than 90%, suggesting that any risk of a second malignancy is far outweighed by the risk of multiple myeloma and its sequelae, Dr. Landgren pointed out.

First-Line Therapy: Italian Experience

In the first of the three studies presented at ASCO 2011, Dr. Palumbo’s group looked at second-cancer rates among patients randomly assigned to first-line therapy with either melphalan and prednisone alone, or to melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance in the international MM-015 trial.

They found that at a median follow-up of 30 months, 12 of 150 (8%) patients on melphalan-prednisone plus lenalidomide with maintenance (MPR-R) developed an invasive second primary malignancy, compared with 9 of 152 patients (5.9%) on the same combination without lenalidomide maintenance (MPR), and 4 of 153 (2.6%) patients on melphalan and prednisone only.

Hematologic malignancies accounted for 7 of the 12 new cancers among patients treated with MPR-R, 5 of 9 on MPR, and 1 of 4 on MP. Solid tumors accounted for the remaining invasive cancers in each group. In addition, one patient on MPR-R, four on MPR, and five on MP developed nonmelanoma skin cancers.

In an additional analysis of 9 pooled experimental studies, the investigators found that among 1,788 patients followed for more than 1 year, the risk of dying of myeloma was greater than 40% out to 7 years compared with about a 2% risk of developing a second hematologic malignancy, and a 3% risk of developing a solid tumor.

Among patients receiving lenalidomide and an alkylating agent, the risk of developing any malignancy was around 7%, and the risk of dying of myeloma was about 27%. The risk of a second malignancy was lower – about 2% out to 6 years– among those patients who did not receive lenalidomide, but their risk of dying of myeloma was about 45%, Dr. Palumbo said.

He also pointed out that in the general population, the risk of a second primary malignancy among 65- to 74-year-olds is around 2% per 100 patient-years, and that the risk doubles among people 85 and older.

First-Line Therapy: BiRD Regimen

In the second study, Dr. Adriana Rossi and her colleagues at Cornell University, New York, and New York–Presbyterian Hospital examined the incidence of second primary cancers in 68 transplant-eligible patients receiving lenalidomide in first-line therapy as part of the BiRD regimen (clarithromycin [Biaxin], lenalidomide, and dexamethasone).

There were five solid tumors (two colon, one metastatic melanoma, one pancreas, and one prostate), but no hematologic malignancies. The melanoma was diagnosed 8 months after the primary myeloma diagnosis; the other cases occurred 25-53 months after the initial myeloma diagnosis (median, 31.2 months). The authors found no association between second primary cancers and a specific multiple myeloma chromosomal abnormality, prior malignancy, transplant status, study status, or sex.

The incidence rate of second primary malignancy was similar to that of all primary cancers reported among people 65 and older in the U.S. Surveillance, Epidemiology, and End Results (SEER) data set spanning 2003-2007, they noted.

"Routine screening and prevention measures should continue as medically indicated for all patients, including examination for skin cancers, and as survival in patients with multiple myeloma continues to improve, so will our understanding of their risk of development of second primary malignancies," she said.

Relapsed/Refractory Disease

The third trial looked at the risk of new primary cancers in patients receiving lenalidomide and dexamethasone for relapsed/refractory disease.

Dr. Meletios Dimopoulos of the University of Athens and colleagues in the international MM-009/010 trials performed a pooled analysis comparing the incidence of second primary cancers in 704 patients who received dexamethasone with either lenalidomide or placebo, and compared them with standard incidence rates.

They found that there were no differences in incidence rates of invasive second primary malignancies between patients in the lenalidomide plus dexamethasone arm or dexamethasone-only arms, and that the incidence rates of second primary cancers in general were low and similar to the background rate among people of similar age in the general population.

Additionally, patients who received lenalidomide and dexamethasone had significantly better overall survival (median, 38 months) despite the fact that about half of all patients in the placebo/dexamathesaone arm (median, 31.6 months) were crossed over to lenalidomide-based therapy (P = .045).

"The overall benefit-risk ratio of the use of lenalidomide in the relapsed/refractory setting remains strongly positive," said the presenter of the abstract, Dr. Ruben Niesvizky of Cornell University.

Lenalidomide is not approved as first-line therapy in the United States. Dr. Palumbo’s study was supported by the Fondazione Neoplasie Sangue Onlus. Dr. Rossi’s and Dr. Dimopoulos’s studies were funded by Celgene. Dr. Palumbo has received honoraria and served as a consultant to Celgene and other companies. Dr. Rossi said she had no relevant financial relationships to disclose. Dr. Dimopoulos disclosed receiving honoraria from Celgene. Dr. Niesvizky said he had received honoraria and research funding from Celgene; he also served in a consulting/advisory role for Celgene and other companies.

CHICAGO – That lenalidomide can improve overall and progression-free survival rates in multiple myeloma patients is evident, but whether the drug also increases their risk of second primary cancers is debatable.

Of three studies looking at the question, only one found an association between secondary primary malignancies and lenalidomide (Revlimid) in first-line therapy, investigators reported at the American Society of Clinical Oncology annual meeting.

And even then the risk was low – far less than the risk of death from multiple myeloma without a lenalidomide-containing regimen, said Dr. Antonio P. Palumbo of the University of Torino (Italy) and the Italian Multiple Myeloma Study Group.

Two other studies – one with 6-year follow-up data on continuous lenalidomide in first-line therapy and the other on lenalidomide in relapsed/refractory disease – failed to spot a signal for second cancer risk.

"I think it’s fair to say that currently we lack clear answers due to small numbers and study limitations," said Dr. C. Ola Landgren of the National Cancer Institute, the invited discussant for all three papers.

"I think we need to put both benefits and risks into the algorithms when we think about these things. ... I also think despite the fact that we don’t have clear data, we always have to discuss these things with our patients, and we as doctors have to stay updated as more information emerges," he said.

Three randomized clinical trials stirred the debate by reporting in separate presentations at the 2010 annual meeting of the American Society of Hematology that they saw more hematologic malignancies in lenalidomide treatment arms than in control groups (McCarthy, P.L. et al, abstract 37; Attal, M. et al, abstract 310; Palumbo, A. et al, abstract 622).

Despite these reports, 25 years after a multiple myeloma diagnosis, the cumulative incidence of all second cancers is about 8%, whereas the cumulative probability of death from competing causes is more than 90%, suggesting that any risk of a second malignancy is far outweighed by the risk of multiple myeloma and its sequelae, Dr. Landgren pointed out.

First-Line Therapy: Italian Experience

In the first of the three studies presented at ASCO 2011, Dr. Palumbo’s group looked at second-cancer rates among patients randomly assigned to first-line therapy with either melphalan and prednisone alone, or to melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance in the international MM-015 trial.

They found that at a median follow-up of 30 months, 12 of 150 (8%) patients on melphalan-prednisone plus lenalidomide with maintenance (MPR-R) developed an invasive second primary malignancy, compared with 9 of 152 patients (5.9%) on the same combination without lenalidomide maintenance (MPR), and 4 of 153 (2.6%) patients on melphalan and prednisone only.

Hematologic malignancies accounted for 7 of the 12 new cancers among patients treated with MPR-R, 5 of 9 on MPR, and 1 of 4 on MP. Solid tumors accounted for the remaining invasive cancers in each group. In addition, one patient on MPR-R, four on MPR, and five on MP developed nonmelanoma skin cancers.

In an additional analysis of 9 pooled experimental studies, the investigators found that among 1,788 patients followed for more than 1 year, the risk of dying of myeloma was greater than 40% out to 7 years compared with about a 2% risk of developing a second hematologic malignancy, and a 3% risk of developing a solid tumor.

Among patients receiving lenalidomide and an alkylating agent, the risk of developing any malignancy was around 7%, and the risk of dying of myeloma was about 27%. The risk of a second malignancy was lower – about 2% out to 6 years– among those patients who did not receive lenalidomide, but their risk of dying of myeloma was about 45%, Dr. Palumbo said.

He also pointed out that in the general population, the risk of a second primary malignancy among 65- to 74-year-olds is around 2% per 100 patient-years, and that the risk doubles among people 85 and older.

First-Line Therapy: BiRD Regimen

In the second study, Dr. Adriana Rossi and her colleagues at Cornell University, New York, and New York–Presbyterian Hospital examined the incidence of second primary cancers in 68 transplant-eligible patients receiving lenalidomide in first-line therapy as part of the BiRD regimen (clarithromycin [Biaxin], lenalidomide, and dexamethasone).

There were five solid tumors (two colon, one metastatic melanoma, one pancreas, and one prostate), but no hematologic malignancies. The melanoma was diagnosed 8 months after the primary myeloma diagnosis; the other cases occurred 25-53 months after the initial myeloma diagnosis (median, 31.2 months). The authors found no association between second primary cancers and a specific multiple myeloma chromosomal abnormality, prior malignancy, transplant status, study status, or sex.

The incidence rate of second primary malignancy was similar to that of all primary cancers reported among people 65 and older in the U.S. Surveillance, Epidemiology, and End Results (SEER) data set spanning 2003-2007, they noted.

"Routine screening and prevention measures should continue as medically indicated for all patients, including examination for skin cancers, and as survival in patients with multiple myeloma continues to improve, so will our understanding of their risk of development of second primary malignancies," she said.

Relapsed/Refractory Disease

The third trial looked at the risk of new primary cancers in patients receiving lenalidomide and dexamethasone for relapsed/refractory disease.

Dr. Meletios Dimopoulos of the University of Athens and colleagues in the international MM-009/010 trials performed a pooled analysis comparing the incidence of second primary cancers in 704 patients who received dexamethasone with either lenalidomide or placebo, and compared them with standard incidence rates.

They found that there were no differences in incidence rates of invasive second primary malignancies between patients in the lenalidomide plus dexamethasone arm or dexamethasone-only arms, and that the incidence rates of second primary cancers in general were low and similar to the background rate among people of similar age in the general population.

Additionally, patients who received lenalidomide and dexamethasone had significantly better overall survival (median, 38 months) despite the fact that about half of all patients in the placebo/dexamathesaone arm (median, 31.6 months) were crossed over to lenalidomide-based therapy (P = .045).

"The overall benefit-risk ratio of the use of lenalidomide in the relapsed/refractory setting remains strongly positive," said the presenter of the abstract, Dr. Ruben Niesvizky of Cornell University.

Lenalidomide is not approved as first-line therapy in the United States. Dr. Palumbo’s study was supported by the Fondazione Neoplasie Sangue Onlus. Dr. Rossi’s and Dr. Dimopoulos’s studies were funded by Celgene. Dr. Palumbo has received honoraria and served as a consultant to Celgene and other companies. Dr. Rossi said she had no relevant financial relationships to disclose. Dr. Dimopoulos disclosed receiving honoraria from Celgene. Dr. Niesvizky said he had received honoraria and research funding from Celgene; he also served in a consulting/advisory role for Celgene and other companies.

CHICAGO – That lenalidomide can improve overall and progression-free survival rates in multiple myeloma patients is evident, but whether the drug also increases their risk of second primary cancers is debatable.

Of three studies looking at the question, only one found an association between secondary primary malignancies and lenalidomide (Revlimid) in first-line therapy, investigators reported at the American Society of Clinical Oncology annual meeting.

And even then the risk was low – far less than the risk of death from multiple myeloma without a lenalidomide-containing regimen, said Dr. Antonio P. Palumbo of the University of Torino (Italy) and the Italian Multiple Myeloma Study Group.

Two other studies – one with 6-year follow-up data on continuous lenalidomide in first-line therapy and the other on lenalidomide in relapsed/refractory disease – failed to spot a signal for second cancer risk.

"I think it’s fair to say that currently we lack clear answers due to small numbers and study limitations," said Dr. C. Ola Landgren of the National Cancer Institute, the invited discussant for all three papers.

"I think we need to put both benefits and risks into the algorithms when we think about these things. ... I also think despite the fact that we don’t have clear data, we always have to discuss these things with our patients, and we as doctors have to stay updated as more information emerges," he said.

Three randomized clinical trials stirred the debate by reporting in separate presentations at the 2010 annual meeting of the American Society of Hematology that they saw more hematologic malignancies in lenalidomide treatment arms than in control groups (McCarthy, P.L. et al, abstract 37; Attal, M. et al, abstract 310; Palumbo, A. et al, abstract 622).

Despite these reports, 25 years after a multiple myeloma diagnosis, the cumulative incidence of all second cancers is about 8%, whereas the cumulative probability of death from competing causes is more than 90%, suggesting that any risk of a second malignancy is far outweighed by the risk of multiple myeloma and its sequelae, Dr. Landgren pointed out.

First-Line Therapy: Italian Experience

In the first of the three studies presented at ASCO 2011, Dr. Palumbo’s group looked at second-cancer rates among patients randomly assigned to first-line therapy with either melphalan and prednisone alone, or to melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance in the international MM-015 trial.

They found that at a median follow-up of 30 months, 12 of 150 (8%) patients on melphalan-prednisone plus lenalidomide with maintenance (MPR-R) developed an invasive second primary malignancy, compared with 9 of 152 patients (5.9%) on the same combination without lenalidomide maintenance (MPR), and 4 of 153 (2.6%) patients on melphalan and prednisone only.

Hematologic malignancies accounted for 7 of the 12 new cancers among patients treated with MPR-R, 5 of 9 on MPR, and 1 of 4 on MP. Solid tumors accounted for the remaining invasive cancers in each group. In addition, one patient on MPR-R, four on MPR, and five on MP developed nonmelanoma skin cancers.

In an additional analysis of 9 pooled experimental studies, the investigators found that among 1,788 patients followed for more than 1 year, the risk of dying of myeloma was greater than 40% out to 7 years compared with about a 2% risk of developing a second hematologic malignancy, and a 3% risk of developing a solid tumor.

Among patients receiving lenalidomide and an alkylating agent, the risk of developing any malignancy was around 7%, and the risk of dying of myeloma was about 27%. The risk of a second malignancy was lower – about 2% out to 6 years– among those patients who did not receive lenalidomide, but their risk of dying of myeloma was about 45%, Dr. Palumbo said.

He also pointed out that in the general population, the risk of a second primary malignancy among 65- to 74-year-olds is around 2% per 100 patient-years, and that the risk doubles among people 85 and older.

First-Line Therapy: BiRD Regimen

In the second study, Dr. Adriana Rossi and her colleagues at Cornell University, New York, and New York–Presbyterian Hospital examined the incidence of second primary cancers in 68 transplant-eligible patients receiving lenalidomide in first-line therapy as part of the BiRD regimen (clarithromycin [Biaxin], lenalidomide, and dexamethasone).

There were five solid tumors (two colon, one metastatic melanoma, one pancreas, and one prostate), but no hematologic malignancies. The melanoma was diagnosed 8 months after the primary myeloma diagnosis; the other cases occurred 25-53 months after the initial myeloma diagnosis (median, 31.2 months). The authors found no association between second primary cancers and a specific multiple myeloma chromosomal abnormality, prior malignancy, transplant status, study status, or sex.

The incidence rate of second primary malignancy was similar to that of all primary cancers reported among people 65 and older in the U.S. Surveillance, Epidemiology, and End Results (SEER) data set spanning 2003-2007, they noted.

"Routine screening and prevention measures should continue as medically indicated for all patients, including examination for skin cancers, and as survival in patients with multiple myeloma continues to improve, so will our understanding of their risk of development of second primary malignancies," she said.

Relapsed/Refractory Disease

The third trial looked at the risk of new primary cancers in patients receiving lenalidomide and dexamethasone for relapsed/refractory disease.

Dr. Meletios Dimopoulos of the University of Athens and colleagues in the international MM-009/010 trials performed a pooled analysis comparing the incidence of second primary cancers in 704 patients who received dexamethasone with either lenalidomide or placebo, and compared them with standard incidence rates.

They found that there were no differences in incidence rates of invasive second primary malignancies between patients in the lenalidomide plus dexamethasone arm or dexamethasone-only arms, and that the incidence rates of second primary cancers in general were low and similar to the background rate among people of similar age in the general population.

Additionally, patients who received lenalidomide and dexamethasone had significantly better overall survival (median, 38 months) despite the fact that about half of all patients in the placebo/dexamathesaone arm (median, 31.6 months) were crossed over to lenalidomide-based therapy (P = .045).

"The overall benefit-risk ratio of the use of lenalidomide in the relapsed/refractory setting remains strongly positive," said the presenter of the abstract, Dr. Ruben Niesvizky of Cornell University.

Lenalidomide is not approved as first-line therapy in the United States. Dr. Palumbo’s study was supported by the Fondazione Neoplasie Sangue Onlus. Dr. Rossi’s and Dr. Dimopoulos’s studies were funded by Celgene. Dr. Palumbo has received honoraria and served as a consultant to Celgene and other companies. Dr. Rossi said she had no relevant financial relationships to disclose. Dr. Dimopoulos disclosed receiving honoraria from Celgene. Dr. Niesvizky said he had received honoraria and research funding from Celgene; he also served in a consulting/advisory role for Celgene and other companies.

CHICAGO – That lenalidomide can improve overall and progression-free survival rates in multiple myeloma patients is evident, but whether the drug also increases their risk of second primary cancers is debatable.

Of three studies looking at the question, only one found an association between secondary primary malignancies and lenalidomide (Revlimid) in first-line therapy, investigators reported at the American Society of Clinical Oncology annual meeting.

And even then the risk was low – far less than the risk of death from multiple myeloma without a lenalidomide-containing regimen, said Dr. Antonio P. Palumbo of the University of Torino (Italy) and the Italian Multiple Myeloma Study Group.

Two other studies – one with 6-year follow-up data on continuous lenalidomide in first-line therapy and the other on lenalidomide in relapsed/refractory disease – failed to spot a signal for second cancer risk.

"I think it’s fair to say that currently we lack clear answers due to small numbers and study limitations," said Dr. C. Ola Landgren of the National Cancer Institute, the invited discussant for all three papers.

"I think we need to put both benefits and risks into the algorithms when we think about these things. ... I also think despite the fact that we don’t have clear data, we always have to discuss these things with our patients, and we as doctors have to stay updated as more information emerges," he said.

Three randomized clinical trials stirred the debate by reporting in separate presentations at the 2010 annual meeting of the American Society of Hematology that they saw more hematologic malignancies in lenalidomide treatment arms than in control groups (McCarthy, P.L. et al, abstract 37; Attal, M. et al, abstract 310; Palumbo, A. et al, abstract 622).

Despite these reports, 25 years after a multiple myeloma diagnosis, the cumulative incidence of all second cancers is about 8%, whereas the cumulative probability of death from competing causes is more than 90%, suggesting that any risk of a second malignancy is far outweighed by the risk of multiple myeloma and its sequelae, Dr. Landgren pointed out.

First-Line Therapy: Italian Experience

In the first of the three studies presented at ASCO 2011, Dr. Palumbo’s group looked at second-cancer rates among patients randomly assigned to first-line therapy with either melphalan and prednisone alone, or to melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance in the international MM-015 trial.

They found that at a median follow-up of 30 months, 12 of 150 (8%) patients on melphalan-prednisone plus lenalidomide with maintenance (MPR-R) developed an invasive second primary malignancy, compared with 9 of 152 patients (5.9%) on the same combination without lenalidomide maintenance (MPR), and 4 of 153 (2.6%) patients on melphalan and prednisone only.

Hematologic malignancies accounted for 7 of the 12 new cancers among patients treated with MPR-R, 5 of 9 on MPR, and 1 of 4 on MP. Solid tumors accounted for the remaining invasive cancers in each group. In addition, one patient on MPR-R, four on MPR, and five on MP developed nonmelanoma skin cancers.

In an additional analysis of 9 pooled experimental studies, the investigators found that among 1,788 patients followed for more than 1 year, the risk of dying of myeloma was greater than 40% out to 7 years compared with about a 2% risk of developing a second hematologic malignancy, and a 3% risk of developing a solid tumor.

Among patients receiving lenalidomide and an alkylating agent, the risk of developing any malignancy was around 7%, and the risk of dying of myeloma was about 27%. The risk of a second malignancy was lower – about 2% out to 6 years– among those patients who did not receive lenalidomide, but their risk of dying of myeloma was about 45%, Dr. Palumbo said.

He also pointed out that in the general population, the risk of a second primary malignancy among 65- to 74-year-olds is around 2% per 100 patient-years, and that the risk doubles among people 85 and older.

First-Line Therapy: BiRD Regimen

In the second study, Dr. Adriana Rossi and her colleagues at Cornell University, New York, and New York–Presbyterian Hospital examined the incidence of second primary cancers in 68 transplant-eligible patients receiving lenalidomide in first-line therapy as part of the BiRD regimen (clarithromycin [Biaxin], lenalidomide, and dexamethasone).

There were five solid tumors (two colon, one metastatic melanoma, one pancreas, and one prostate), but no hematologic malignancies. The melanoma was diagnosed 8 months after the primary myeloma diagnosis; the other cases occurred 25-53 months after the initial myeloma diagnosis (median, 31.2 months). The authors found no association between second primary cancers and a specific multiple myeloma chromosomal abnormality, prior malignancy, transplant status, study status, or sex.

The incidence rate of second primary malignancy was similar to that of all primary cancers reported among people 65 and older in the U.S. Surveillance, Epidemiology, and End Results (SEER) data set spanning 2003-2007, they noted.

"Routine screening and prevention measures should continue as medically indicated for all patients, including examination for skin cancers, and as survival in patients with multiple myeloma continues to improve, so will our understanding of their risk of development of second primary malignancies," she said.

Relapsed/Refractory Disease

The third trial looked at the risk of new primary cancers in patients receiving lenalidomide and dexamethasone for relapsed/refractory disease.

Dr. Meletios Dimopoulos of the University of Athens and colleagues in the international MM-009/010 trials performed a pooled analysis comparing the incidence of second primary cancers in 704 patients who received dexamethasone with either lenalidomide or placebo, and compared them with standard incidence rates.

They found that there were no differences in incidence rates of invasive second primary malignancies between patients in the lenalidomide plus dexamethasone arm or dexamethasone-only arms, and that the incidence rates of second primary cancers in general were low and similar to the background rate among people of similar age in the general population.

Additionally, patients who received lenalidomide and dexamethasone had significantly better overall survival (median, 38 months) despite the fact that about half of all patients in the placebo/dexamathesaone arm (median, 31.6 months) were crossed over to lenalidomide-based therapy (P = .045).

"The overall benefit-risk ratio of the use of lenalidomide in the relapsed/refractory setting remains strongly positive," said the presenter of the abstract, Dr. Ruben Niesvizky of Cornell University.

Lenalidomide is not approved as first-line therapy in the United States. Dr. Palumbo’s study was supported by the Fondazione Neoplasie Sangue Onlus. Dr. Rossi’s and Dr. Dimopoulos’s studies were funded by Celgene. Dr. Palumbo has received honoraria and served as a consultant to Celgene and other companies. Dr. Rossi said she had no relevant financial relationships to disclose. Dr. Dimopoulos disclosed receiving honoraria from Celgene. Dr. Niesvizky said he had received honoraria and research funding from Celgene; he also served in a consulting/advisory role for Celgene and other companies.

CHICAGO – That lenalidomide can improve overall and progression-free survival rates in multiple myeloma patients is evident, but whether the drug also increases their risk of second primary cancers is debatable.

Of three studies looking at the question, only one found an association between secondary primary malignancies and lenalidomide (Revlimid) in first-line therapy, investigators reported at the American Society of Clinical Oncology annual meeting.

And even then the risk was low – far less than the risk of death from multiple myeloma without a lenalidomide-containing regimen, said Dr. Antonio P. Palumbo of the University of Torino (Italy) and the Italian Multiple Myeloma Study Group.

Two other studies – one with 6-year follow-up data on continuous lenalidomide in first-line therapy and the other on lenalidomide in relapsed/refractory disease – failed to spot a signal for second cancer risk.

"I think it’s fair to say that currently we lack clear answers due to small numbers and study limitations," said Dr. C. Ola Landgren of the National Cancer Institute, the invited discussant for all three papers.

"I think we need to put both benefits and risks into the algorithms when we think about these things. ... I also think despite the fact that we don’t have clear data, we always have to discuss these things with our patients, and we as doctors have to stay updated as more information emerges," he said.

Three randomized clinical trials stirred the debate by reporting in separate presentations at the 2010 annual meeting of the American Society of Hematology that they saw more hematologic malignancies in lenalidomide treatment arms than in control groups (McCarthy, P.L. et al, abstract 37; Attal, M. et al, abstract 310; Palumbo, A. et al, abstract 622).

Despite these reports, 25 years after a multiple myeloma diagnosis, the cumulative incidence of all second cancers is about 8%, whereas the cumulative probability of death from competing causes is more than 90%, suggesting that any risk of a second malignancy is far outweighed by the risk of multiple myeloma and its sequelae, Dr. Landgren pointed out.

First-Line Therapy: Italian Experience

In the first of the three studies presented at ASCO 2011, Dr. Palumbo’s group looked at second-cancer rates among patients randomly assigned to first-line therapy with either melphalan and prednisone alone, or to melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance in the international MM-015 trial.

They found that at a median follow-up of 30 months, 12 of 150 (8%) patients on melphalan-prednisone plus lenalidomide with maintenance (MPR-R) developed an invasive second primary malignancy, compared with 9 of 152 patients (5.9%) on the same combination without lenalidomide maintenance (MPR), and 4 of 153 (2.6%) patients on melphalan and prednisone only.

Hematologic malignancies accounted for 7 of the 12 new cancers among patients treated with MPR-R, 5 of 9 on MPR, and 1 of 4 on MP. Solid tumors accounted for the remaining invasive cancers in each group. In addition, one patient on MPR-R, four on MPR, and five on MP developed nonmelanoma skin cancers.

In an additional analysis of 9 pooled experimental studies, the investigators found that among 1,788 patients followed for more than 1 year, the risk of dying of myeloma was greater than 40% out to 7 years compared with about a 2% risk of developing a second hematologic malignancy, and a 3% risk of developing a solid tumor.

Among patients receiving lenalidomide and an alkylating agent, the risk of developing any malignancy was around 7%, and the risk of dying of myeloma was about 27%. The risk of a second malignancy was lower – about 2% out to 6 years– among those patients who did not receive lenalidomide, but their risk of dying of myeloma was about 45%, Dr. Palumbo said.

He also pointed out that in the general population, the risk of a second primary malignancy among 65- to 74-year-olds is around 2% per 100 patient-years, and that the risk doubles among people 85 and older.

First-Line Therapy: BiRD Regimen

In the second study, Dr. Adriana Rossi and her colleagues at Cornell University, New York, and New York–Presbyterian Hospital examined the incidence of second primary cancers in 68 transplant-eligible patients receiving lenalidomide in first-line therapy as part of the BiRD regimen (clarithromycin [Biaxin], lenalidomide, and dexamethasone).

There were five solid tumors (two colon, one metastatic melanoma, one pancreas, and one prostate), but no hematologic malignancies. The melanoma was diagnosed 8 months after the primary myeloma diagnosis; the other cases occurred 25-53 months after the initial myeloma diagnosis (median, 31.2 months). The authors found no association between second primary cancers and a specific multiple myeloma chromosomal abnormality, prior malignancy, transplant status, study status, or sex.

The incidence rate of second primary malignancy was similar to that of all primary cancers reported among people 65 and older in the U.S. Surveillance, Epidemiology, and End Results (SEER) data set spanning 2003-2007, they noted.

"Routine screening and prevention measures should continue as medically indicated for all patients, including examination for skin cancers, and as survival in patients with multiple myeloma continues to improve, so will our understanding of their risk of development of second primary malignancies," she said.

Relapsed/Refractory Disease

The third trial looked at the risk of new primary cancers in patients receiving lenalidomide and dexamethasone for relapsed/refractory disease.

Dr. Meletios Dimopoulos of the University of Athens and colleagues in the international MM-009/010 trials performed a pooled analysis comparing the incidence of second primary cancers in 704 patients who received dexamethasone with either lenalidomide or placebo, and compared them with standard incidence rates.

They found that there were no differences in incidence rates of invasive second primary malignancies between patients in the lenalidomide plus dexamethasone arm or dexamethasone-only arms, and that the incidence rates of second primary cancers in general were low and similar to the background rate among people of similar age in the general population.

Additionally, patients who received lenalidomide and dexamethasone had significantly better overall survival (median, 38 months) despite the fact that about half of all patients in the placebo/dexamathesaone arm (median, 31.6 months) were crossed over to lenalidomide-based therapy (P = .045).

"The overall benefit-risk ratio of the use of lenalidomide in the relapsed/refractory setting remains strongly positive," said the presenter of the abstract, Dr. Ruben Niesvizky of Cornell University.

Lenalidomide is not approved as first-line therapy in the United States. Dr. Palumbo’s study was supported by the Fondazione Neoplasie Sangue Onlus. Dr. Rossi’s and Dr. Dimopoulos’s studies were funded by Celgene. Dr. Palumbo has received honoraria and served as a consultant to Celgene and other companies. Dr. Rossi said she had no relevant financial relationships to disclose. Dr. Dimopoulos disclosed receiving honoraria from Celgene. Dr. Niesvizky said he had received honoraria and research funding from Celgene; he also served in a consulting/advisory role for Celgene and other companies.

CHICAGO – That lenalidomide can improve overall and progression-free survival rates in multiple myeloma patients is evident, but whether the drug also increases their risk of second primary cancers is debatable.

Of three studies looking at the question, only one found an association between secondary primary malignancies and lenalidomide (Revlimid) in first-line therapy, investigators reported at the American Society of Clinical Oncology annual meeting.

And even then the risk was low – far less than the risk of death from multiple myeloma without a lenalidomide-containing regimen, said Dr. Antonio P. Palumbo of the University of Torino (Italy) and the Italian Multiple Myeloma Study Group.

Two other studies – one with 6-year follow-up data on continuous lenalidomide in first-line therapy and the other on lenalidomide in relapsed/refractory disease – failed to spot a signal for second cancer risk.

"I think it’s fair to say that currently we lack clear answers due to small numbers and study limitations," said Dr. C. Ola Landgren of the National Cancer Institute, the invited discussant for all three papers.

"I think we need to put both benefits and risks into the algorithms when we think about these things. ... I also think despite the fact that we don’t have clear data, we always have to discuss these things with our patients, and we as doctors have to stay updated as more information emerges," he said.

Three randomized clinical trials stirred the debate by reporting in separate presentations at the 2010 annual meeting of the American Society of Hematology that they saw more hematologic malignancies in lenalidomide treatment arms than in control groups (McCarthy, P.L. et al, abstract 37; Attal, M. et al, abstract 310; Palumbo, A. et al, abstract 622).

Despite these reports, 25 years after a multiple myeloma diagnosis, the cumulative incidence of all second cancers is about 8%, whereas the cumulative probability of death from competing causes is more than 90%, suggesting that any risk of a second malignancy is far outweighed by the risk of multiple myeloma and its sequelae, Dr. Landgren pointed out.

First-Line Therapy: Italian Experience

In the first of the three studies presented at ASCO 2011, Dr. Palumbo’s group looked at second-cancer rates among patients randomly assigned to first-line therapy with either melphalan and prednisone alone, or to melphalan, prednisone, and lenalidomide with or without lenalidomide maintenance in the international MM-015 trial.

They found that at a median follow-up of 30 months, 12 of 150 (8%) patients on melphalan-prednisone plus lenalidomide with maintenance (MPR-R) developed an invasive second primary malignancy, compared with 9 of 152 patients (5.9%) on the same combination without lenalidomide maintenance (MPR), and 4 of 153 (2.6%) patients on melphalan and prednisone only.

Hematologic malignancies accounted for 7 of the 12 new cancers among patients treated with MPR-R, 5 of 9 on MPR, and 1 of 4 on MP. Solid tumors accounted for the remaining invasive cancers in each group. In addition, one patient on MPR-R, four on MPR, and five on MP developed nonmelanoma skin cancers.

In an additional analysis of 9 pooled experimental studies, the investigators found that among 1,788 patients followed for more than 1 year, the risk of dying of myeloma was greater than 40% out to 7 years compared with about a 2% risk of developing a second hematologic malignancy, and a 3% risk of developing a solid tumor.

Among patients receiving lenalidomide and an alkylating agent, the risk of developing any malignancy was around 7%, and the risk of dying of myeloma was about 27%. The risk of a second malignancy was lower – about 2% out to 6 years– among those patients who did not receive lenalidomide, but their risk of dying of myeloma was about 45%, Dr. Palumbo said.

He also pointed out that in the general population, the risk of a second primary malignancy among 65- to 74-year-olds is around 2% per 100 patient-years, and that the risk doubles among people 85 and older.

First-Line Therapy: BiRD Regimen

In the second study, Dr. Adriana Rossi and her colleagues at Cornell University, New York, and New York–Presbyterian Hospital examined the incidence of second primary cancers in 68 transplant-eligible patients receiving lenalidomide in first-line therapy as part of the BiRD regimen (clarithromycin [Biaxin], lenalidomide, and dexamethasone).

There were five solid tumors (two colon, one metastatic melanoma, one pancreas, and one prostate), but no hematologic malignancies. The melanoma was diagnosed 8 months after the primary myeloma diagnosis; the other cases occurred 25-53 months after the initial myeloma diagnosis (median, 31.2 months). The authors found no association between second primary cancers and a specific multiple myeloma chromosomal abnormality, prior malignancy, transplant status, study status, or sex.

The incidence rate of second primary malignancy was similar to that of all primary cancers reported among people 65 and older in the U.S. Surveillance, Epidemiology, and End Results (SEER) data set spanning 2003-2007, they noted.

"Routine screening and prevention measures should continue as medically indicated for all patients, including examination for skin cancers, and as survival in patients with multiple myeloma continues to improve, so will our understanding of their risk of development of second primary malignancies," she said.

Relapsed/Refractory Disease

The third trial looked at the risk of new primary cancers in patients receiving lenalidomide and dexamethasone for relapsed/refractory disease.

Dr. Meletios Dimopoulos of the University of Athens and colleagues in the international MM-009/010 trials performed a pooled analysis comparing the incidence of second primary cancers in 704 patients who received dexamethasone with either lenalidomide or placebo, and compared them with standard incidence rates.

They found that there were no differences in incidence rates of invasive second primary malignancies between patients in the lenalidomide plus dexamethasone arm or dexamethasone-only arms, and that the incidence rates of second primary cancers in general were low and similar to the background rate among people of similar age in the general population.

Additionally, patients who received lenalidomide and dexamethasone had significantly better overall survival (median, 38 months) despite the fact that about half of all patients in the placebo/dexamathesaone arm (median, 31.6 months) were crossed over to lenalidomide-based therapy (P = .045).

"The overall benefit-risk ratio of the use of lenalidomide in the relapsed/refractory setting remains strongly positive," said the presenter of the abstract, Dr. Ruben Niesvizky of Cornell University.

Lenalidomide is not approved as first-line therapy in the United States. Dr. Palumbo’s study was supported by the Fondazione Neoplasie Sangue Onlus. Dr. Rossi’s and Dr. Dimopoulos’s studies were funded by Celgene. Dr. Palumbo has received honoraria and served as a consultant to Celgene and other companies. Dr. Rossi said she had no relevant financial relationships to disclose. Dr. Dimopoulos disclosed receiving honoraria from Celgene. Dr. Niesvizky said he had received honoraria and research funding from Celgene; he also served in a consulting/advisory role for Celgene and other companies.

CHICAGO – Prophylaxis with semuloparin, an experimental ultralow-molecular-weight heparin, achieved a significant 64% reduction in relative risk for venous thromboembolism events among cancer patients undergoing chemotherapy in a large, randomized, double-blind, phase III trial called SAVE-ONCO.

An intent-to-treat analysis found that the rate of venous thromboembolism (VTE) events – a composite of symptomatic deep vein thrombosis, any pulmonary embolism, and VTE-related death – was 1.2% in patients treated with semuloparin vs. 3.4% in a control group treated with placebo (hazard ratio, 0.36; P less than .0001).

Benefits trended in favor of semuloparin for all components of the composite end point, including any pulmonary embolism (odds ratio, 0.41) and VTE-related death (OR, 0.77), reported Dr. Daniel J. George, who presented the paper on behalf of Dr. Giancarlo Agnelli of Perugia (Italy) University at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of clinically relevant bleeding was higher at 2.8% with semuloparin vs. 2% for placebo, Dr. George added that a safety analysis found that the incidence of major bleeding was similarly low, at 1.2% and 1.1%, respectively.

Based on the trial results, Dr. Elias Zerhouni, president of global research and development at trial sponsor Sanofi-Aventis, announced that the company plans "to submit semuloparin for regulatory filing" in the third quarter of 2011. Still investigational, the selectively engineered anticoagulant has high anti–coagulation factor Xa activity and minimal anti–coagulation factor IIa activity with a half-life of 16-20 hours.

Although it is advocated for cancer patients who are hospitalized or undergoing surgery and is not contraindicated for anticoagulation, the routine prophylaxis of ambulatory cancer patients receiving chemotherapy is not currently recommended.

"So this leaves us with the question, Which cancer patients should we now consider for thromboprophylaxis?" said Dr. George of Duke University Medical Center in Durham, N.C. "Already our guidelines suggest that those patients with cancer undergoing major surgery, or hospitalized, or acutely ill, ought to be anticoagulated with low-molecular-weight heparin during those periods of time.

"I would now submit that the SAVE ONCO data would support having patients initiating chemotherapy, in the setting of locally advanced or metastatic disease, as a third population that we could consider for thromboprophylaxis," he said.

Although discussant Dr. Vered Stearns of Johns Hopkins University in Baltimore viewed the findings favorably, she cautioned that "SAVE-ONCO should not change current practice for the overall population."

Dr. Stearns emphasized that predictive models are needed to determine which ambulatory patients are at the highest risk for VTE, "and who should be offered prophylaxis in the context of expected clinical outcomes." Biomarkers such as circulating coagulating factors are also important, she added.

"Semuloparin is an efficacious and safe agent. That’s very exciting," Dr. Stearns said. "The reduction in [VTE] events is consistent throughout the report, and my understanding is [that] the group is conducting subgroup analysis and evaluation of predictive markers that may help us select the population that would benefit from primary prophylaxis."

A multinational study, the SAVE-ONCO trial enrolled 3,200 patients who were at high risk of VTE. Participants had metastatic or locally advanced solid tumors such as lung, pancreas, stomach, colon/rectal, bladder, or ovarian tumors for which they were starting a new course of chemotherapy with minimum treatment intent of 3 months.

Patients were randomized 1:1 to standard-care chemotherapy plus either placebo or semuloparin 20 mg subcutaneously once daily for the length of their chemotherapy.

Patient characteristics were well balanced across both arms: The median age was 60 years, and 60% of patients were men. More than two-thirds had metastatic disease. Lung cancer was the most common tumor type (36%) followed by colon/rectal cancer (28%). The remainder had cancer of the stomach, ovary, pancreas, or bladder. Treatment duration was approximately 3.5 months in both groups.

In response to audience questions, Dr. George said that the study did not show a survival benefit, but "there is likely a subset of patients" for whom this made a dramatic impact in their early morbidity and mortality.

The study did not address cost, but that will be a factor if prophylaxis is introduced for a large population of cancer patients, he acknowledged, "It really comes down to safety and cost," he said.

The study was sponsored by Sanofi-Aventis. Dr. George disclosed numerous relationships with pharmaceutical companies, including consultant or advisory role, honoraria, and speakers bureau with Sanofi-Aventis. Dr. Agnelli disclosed receiving honoraria from Sanofi-Aventis and relationships with other companies. Dr. Stearns disclosed honoraria and research funding from other companies.

CHICAGO – Prophylaxis with semuloparin, an experimental ultralow-molecular-weight heparin, achieved a significant 64% reduction in relative risk for venous thromboembolism events among cancer patients undergoing chemotherapy in a large, randomized, double-blind, phase III trial called SAVE-ONCO.

An intent-to-treat analysis found that the rate of venous thromboembolism (VTE) events – a composite of symptomatic deep vein thrombosis, any pulmonary embolism, and VTE-related death – was 1.2% in patients treated with semuloparin vs. 3.4% in a control group treated with placebo (hazard ratio, 0.36; P less than .0001).

Benefits trended in favor of semuloparin for all components of the composite end point, including any pulmonary embolism (odds ratio, 0.41) and VTE-related death (OR, 0.77), reported Dr. Daniel J. George, who presented the paper on behalf of Dr. Giancarlo Agnelli of Perugia (Italy) University at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of clinically relevant bleeding was higher at 2.8% with semuloparin vs. 2% for placebo, Dr. George added that a safety analysis found that the incidence of major bleeding was similarly low, at 1.2% and 1.1%, respectively.

Based on the trial results, Dr. Elias Zerhouni, president of global research and development at trial sponsor Sanofi-Aventis, announced that the company plans "to submit semuloparin for regulatory filing" in the third quarter of 2011. Still investigational, the selectively engineered anticoagulant has high anti–coagulation factor Xa activity and minimal anti–coagulation factor IIa activity with a half-life of 16-20 hours.

Although it is advocated for cancer patients who are hospitalized or undergoing surgery and is not contraindicated for anticoagulation, the routine prophylaxis of ambulatory cancer patients receiving chemotherapy is not currently recommended.

"So this leaves us with the question, Which cancer patients should we now consider for thromboprophylaxis?" said Dr. George of Duke University Medical Center in Durham, N.C. "Already our guidelines suggest that those patients with cancer undergoing major surgery, or hospitalized, or acutely ill, ought to be anticoagulated with low-molecular-weight heparin during those periods of time.

"I would now submit that the SAVE ONCO data would support having patients initiating chemotherapy, in the setting of locally advanced or metastatic disease, as a third population that we could consider for thromboprophylaxis," he said.

Although discussant Dr. Vered Stearns of Johns Hopkins University in Baltimore viewed the findings favorably, she cautioned that "SAVE-ONCO should not change current practice for the overall population."

Dr. Stearns emphasized that predictive models are needed to determine which ambulatory patients are at the highest risk for VTE, "and who should be offered prophylaxis in the context of expected clinical outcomes." Biomarkers such as circulating coagulating factors are also important, she added.

"Semuloparin is an efficacious and safe agent. That’s very exciting," Dr. Stearns said. "The reduction in [VTE] events is consistent throughout the report, and my understanding is [that] the group is conducting subgroup analysis and evaluation of predictive markers that may help us select the population that would benefit from primary prophylaxis."

A multinational study, the SAVE-ONCO trial enrolled 3,200 patients who were at high risk of VTE. Participants had metastatic or locally advanced solid tumors such as lung, pancreas, stomach, colon/rectal, bladder, or ovarian tumors for which they were starting a new course of chemotherapy with minimum treatment intent of 3 months.

Patients were randomized 1:1 to standard-care chemotherapy plus either placebo or semuloparin 20 mg subcutaneously once daily for the length of their chemotherapy.

Patient characteristics were well balanced across both arms: The median age was 60 years, and 60% of patients were men. More than two-thirds had metastatic disease. Lung cancer was the most common tumor type (36%) followed by colon/rectal cancer (28%). The remainder had cancer of the stomach, ovary, pancreas, or bladder. Treatment duration was approximately 3.5 months in both groups.

In response to audience questions, Dr. George said that the study did not show a survival benefit, but "there is likely a subset of patients" for whom this made a dramatic impact in their early morbidity and mortality.

The study did not address cost, but that will be a factor if prophylaxis is introduced for a large population of cancer patients, he acknowledged, "It really comes down to safety and cost," he said.

The study was sponsored by Sanofi-Aventis. Dr. George disclosed numerous relationships with pharmaceutical companies, including consultant or advisory role, honoraria, and speakers bureau with Sanofi-Aventis. Dr. Agnelli disclosed receiving honoraria from Sanofi-Aventis and relationships with other companies. Dr. Stearns disclosed honoraria and research funding from other companies.

CHICAGO – Prophylaxis with semuloparin, an experimental ultralow-molecular-weight heparin, achieved a significant 64% reduction in relative risk for venous thromboembolism events among cancer patients undergoing chemotherapy in a large, randomized, double-blind, phase III trial called SAVE-ONCO.

An intent-to-treat analysis found that the rate of venous thromboembolism (VTE) events – a composite of symptomatic deep vein thrombosis, any pulmonary embolism, and VTE-related death – was 1.2% in patients treated with semuloparin vs. 3.4% in a control group treated with placebo (hazard ratio, 0.36; P less than .0001).

Benefits trended in favor of semuloparin for all components of the composite end point, including any pulmonary embolism (odds ratio, 0.41) and VTE-related death (OR, 0.77), reported Dr. Daniel J. George, who presented the paper on behalf of Dr. Giancarlo Agnelli of Perugia (Italy) University at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of clinically relevant bleeding was higher at 2.8% with semuloparin vs. 2% for placebo, Dr. George added that a safety analysis found that the incidence of major bleeding was similarly low, at 1.2% and 1.1%, respectively.

Based on the trial results, Dr. Elias Zerhouni, president of global research and development at trial sponsor Sanofi-Aventis, announced that the company plans "to submit semuloparin for regulatory filing" in the third quarter of 2011. Still investigational, the selectively engineered anticoagulant has high anti–coagulation factor Xa activity and minimal anti–coagulation factor IIa activity with a half-life of 16-20 hours.

Although it is advocated for cancer patients who are hospitalized or undergoing surgery and is not contraindicated for anticoagulation, the routine prophylaxis of ambulatory cancer patients receiving chemotherapy is not currently recommended.

"So this leaves us with the question, Which cancer patients should we now consider for thromboprophylaxis?" said Dr. George of Duke University Medical Center in Durham, N.C. "Already our guidelines suggest that those patients with cancer undergoing major surgery, or hospitalized, or acutely ill, ought to be anticoagulated with low-molecular-weight heparin during those periods of time.

"I would now submit that the SAVE ONCO data would support having patients initiating chemotherapy, in the setting of locally advanced or metastatic disease, as a third population that we could consider for thromboprophylaxis," he said.

Although discussant Dr. Vered Stearns of Johns Hopkins University in Baltimore viewed the findings favorably, she cautioned that "SAVE-ONCO should not change current practice for the overall population."

Dr. Stearns emphasized that predictive models are needed to determine which ambulatory patients are at the highest risk for VTE, "and who should be offered prophylaxis in the context of expected clinical outcomes." Biomarkers such as circulating coagulating factors are also important, she added.

"Semuloparin is an efficacious and safe agent. That’s very exciting," Dr. Stearns said. "The reduction in [VTE] events is consistent throughout the report, and my understanding is [that] the group is conducting subgroup analysis and evaluation of predictive markers that may help us select the population that would benefit from primary prophylaxis."

A multinational study, the SAVE-ONCO trial enrolled 3,200 patients who were at high risk of VTE. Participants had metastatic or locally advanced solid tumors such as lung, pancreas, stomach, colon/rectal, bladder, or ovarian tumors for which they were starting a new course of chemotherapy with minimum treatment intent of 3 months.

Patients were randomized 1:1 to standard-care chemotherapy plus either placebo or semuloparin 20 mg subcutaneously once daily for the length of their chemotherapy.

Patient characteristics were well balanced across both arms: The median age was 60 years, and 60% of patients were men. More than two-thirds had metastatic disease. Lung cancer was the most common tumor type (36%) followed by colon/rectal cancer (28%). The remainder had cancer of the stomach, ovary, pancreas, or bladder. Treatment duration was approximately 3.5 months in both groups.

In response to audience questions, Dr. George said that the study did not show a survival benefit, but "there is likely a subset of patients" for whom this made a dramatic impact in their early morbidity and mortality.

The study did not address cost, but that will be a factor if prophylaxis is introduced for a large population of cancer patients, he acknowledged, "It really comes down to safety and cost," he said.

The study was sponsored by Sanofi-Aventis. Dr. George disclosed numerous relationships with pharmaceutical companies, including consultant or advisory role, honoraria, and speakers bureau with Sanofi-Aventis. Dr. Agnelli disclosed receiving honoraria from Sanofi-Aventis and relationships with other companies. Dr. Stearns disclosed honoraria and research funding from other companies.

CHICAGO – Prophylaxis with semuloparin, an experimental ultralow-molecular-weight heparin, achieved a significant 64% reduction in relative risk for venous thromboembolism events among cancer patients undergoing chemotherapy in a large, randomized, double-blind, phase III trial called SAVE-ONCO.

An intent-to-treat analysis found that the rate of venous thromboembolism (VTE) events – a composite of symptomatic deep vein thrombosis, any pulmonary embolism, and VTE-related death – was 1.2% in patients treated with semuloparin vs. 3.4% in a control group treated with placebo (hazard ratio, 0.36; P less than .0001).

Benefits trended in favor of semuloparin for all components of the composite end point, including any pulmonary embolism (odds ratio, 0.41) and VTE-related death (OR, 0.77), reported Dr. Daniel J. George, who presented the paper on behalf of Dr. Giancarlo Agnelli of Perugia (Italy) University at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of clinically relevant bleeding was higher at 2.8% with semuloparin vs. 2% for placebo, Dr. George added that a safety analysis found that the incidence of major bleeding was similarly low, at 1.2% and 1.1%, respectively.

Based on the trial results, Dr. Elias Zerhouni, president of global research and development at trial sponsor Sanofi-Aventis, announced that the company plans "to submit semuloparin for regulatory filing" in the third quarter of 2011. Still investigational, the selectively engineered anticoagulant has high anti–coagulation factor Xa activity and minimal anti–coagulation factor IIa activity with a half-life of 16-20 hours.

Although it is advocated for cancer patients who are hospitalized or undergoing surgery and is not contraindicated for anticoagulation, the routine prophylaxis of ambulatory cancer patients receiving chemotherapy is not currently recommended.

"So this leaves us with the question, Which cancer patients should we now consider for thromboprophylaxis?" said Dr. George of Duke University Medical Center in Durham, N.C. "Already our guidelines suggest that those patients with cancer undergoing major surgery, or hospitalized, or acutely ill, ought to be anticoagulated with low-molecular-weight heparin during those periods of time.

"I would now submit that the SAVE ONCO data would support having patients initiating chemotherapy, in the setting of locally advanced or metastatic disease, as a third population that we could consider for thromboprophylaxis," he said.

Although discussant Dr. Vered Stearns of Johns Hopkins University in Baltimore viewed the findings favorably, she cautioned that "SAVE-ONCO should not change current practice for the overall population."

Dr. Stearns emphasized that predictive models are needed to determine which ambulatory patients are at the highest risk for VTE, "and who should be offered prophylaxis in the context of expected clinical outcomes." Biomarkers such as circulating coagulating factors are also important, she added.

"Semuloparin is an efficacious and safe agent. That’s very exciting," Dr. Stearns said. "The reduction in [VTE] events is consistent throughout the report, and my understanding is [that] the group is conducting subgroup analysis and evaluation of predictive markers that may help us select the population that would benefit from primary prophylaxis."

A multinational study, the SAVE-ONCO trial enrolled 3,200 patients who were at high risk of VTE. Participants had metastatic or locally advanced solid tumors such as lung, pancreas, stomach, colon/rectal, bladder, or ovarian tumors for which they were starting a new course of chemotherapy with minimum treatment intent of 3 months.

Patients were randomized 1:1 to standard-care chemotherapy plus either placebo or semuloparin 20 mg subcutaneously once daily for the length of their chemotherapy.

Patient characteristics were well balanced across both arms: The median age was 60 years, and 60% of patients were men. More than two-thirds had metastatic disease. Lung cancer was the most common tumor type (36%) followed by colon/rectal cancer (28%). The remainder had cancer of the stomach, ovary, pancreas, or bladder. Treatment duration was approximately 3.5 months in both groups.

In response to audience questions, Dr. George said that the study did not show a survival benefit, but "there is likely a subset of patients" for whom this made a dramatic impact in their early morbidity and mortality.

The study did not address cost, but that will be a factor if prophylaxis is introduced for a large population of cancer patients, he acknowledged, "It really comes down to safety and cost," he said.

The study was sponsored by Sanofi-Aventis. Dr. George disclosed numerous relationships with pharmaceutical companies, including consultant or advisory role, honoraria, and speakers bureau with Sanofi-Aventis. Dr. Agnelli disclosed receiving honoraria from Sanofi-Aventis and relationships with other companies. Dr. Stearns disclosed honoraria and research funding from other companies.

CHICAGO – Prophylaxis with semuloparin, an experimental ultralow-molecular-weight heparin, achieved a significant 64% reduction in relative risk for venous thromboembolism events among cancer patients undergoing chemotherapy in a large, randomized, double-blind, phase III trial called SAVE-ONCO.

An intent-to-treat analysis found that the rate of venous thromboembolism (VTE) events – a composite of symptomatic deep vein thrombosis, any pulmonary embolism, and VTE-related death – was 1.2% in patients treated with semuloparin vs. 3.4% in a control group treated with placebo (hazard ratio, 0.36; P less than .0001).

Benefits trended in favor of semuloparin for all components of the composite end point, including any pulmonary embolism (odds ratio, 0.41) and VTE-related death (OR, 0.77), reported Dr. Daniel J. George, who presented the paper on behalf of Dr. Giancarlo Agnelli of Perugia (Italy) University at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of clinically relevant bleeding was higher at 2.8% with semuloparin vs. 2% for placebo, Dr. George added that a safety analysis found that the incidence of major bleeding was similarly low, at 1.2% and 1.1%, respectively.

Based on the trial results, Dr. Elias Zerhouni, president of global research and development at trial sponsor Sanofi-Aventis, announced that the company plans "to submit semuloparin for regulatory filing" in the third quarter of 2011. Still investigational, the selectively engineered anticoagulant has high anti–coagulation factor Xa activity and minimal anti–coagulation factor IIa activity with a half-life of 16-20 hours.

Although it is advocated for cancer patients who are hospitalized or undergoing surgery and is not contraindicated for anticoagulation, the routine prophylaxis of ambulatory cancer patients receiving chemotherapy is not currently recommended.

"So this leaves us with the question, Which cancer patients should we now consider for thromboprophylaxis?" said Dr. George of Duke University Medical Center in Durham, N.C. "Already our guidelines suggest that those patients with cancer undergoing major surgery, or hospitalized, or acutely ill, ought to be anticoagulated with low-molecular-weight heparin during those periods of time.

"I would now submit that the SAVE ONCO data would support having patients initiating chemotherapy, in the setting of locally advanced or metastatic disease, as a third population that we could consider for thromboprophylaxis," he said.

Although discussant Dr. Vered Stearns of Johns Hopkins University in Baltimore viewed the findings favorably, she cautioned that "SAVE-ONCO should not change current practice for the overall population."

Dr. Stearns emphasized that predictive models are needed to determine which ambulatory patients are at the highest risk for VTE, "and who should be offered prophylaxis in the context of expected clinical outcomes." Biomarkers such as circulating coagulating factors are also important, she added.

"Semuloparin is an efficacious and safe agent. That’s very exciting," Dr. Stearns said. "The reduction in [VTE] events is consistent throughout the report, and my understanding is [that] the group is conducting subgroup analysis and evaluation of predictive markers that may help us select the population that would benefit from primary prophylaxis."

A multinational study, the SAVE-ONCO trial enrolled 3,200 patients who were at high risk of VTE. Participants had metastatic or locally advanced solid tumors such as lung, pancreas, stomach, colon/rectal, bladder, or ovarian tumors for which they were starting a new course of chemotherapy with minimum treatment intent of 3 months.

Patients were randomized 1:1 to standard-care chemotherapy plus either placebo or semuloparin 20 mg subcutaneously once daily for the length of their chemotherapy.

Patient characteristics were well balanced across both arms: The median age was 60 years, and 60% of patients were men. More than two-thirds had metastatic disease. Lung cancer was the most common tumor type (36%) followed by colon/rectal cancer (28%). The remainder had cancer of the stomach, ovary, pancreas, or bladder. Treatment duration was approximately 3.5 months in both groups.

In response to audience questions, Dr. George said that the study did not show a survival benefit, but "there is likely a subset of patients" for whom this made a dramatic impact in their early morbidity and mortality.

The study did not address cost, but that will be a factor if prophylaxis is introduced for a large population of cancer patients, he acknowledged, "It really comes down to safety and cost," he said.

The study was sponsored by Sanofi-Aventis. Dr. George disclosed numerous relationships with pharmaceutical companies, including consultant or advisory role, honoraria, and speakers bureau with Sanofi-Aventis. Dr. Agnelli disclosed receiving honoraria from Sanofi-Aventis and relationships with other companies. Dr. Stearns disclosed honoraria and research funding from other companies.

CHICAGO – Prophylaxis with semuloparin, an experimental ultralow-molecular-weight heparin, achieved a significant 64% reduction in relative risk for venous thromboembolism events among cancer patients undergoing chemotherapy in a large, randomized, double-blind, phase III trial called SAVE-ONCO.

An intent-to-treat analysis found that the rate of venous thromboembolism (VTE) events – a composite of symptomatic deep vein thrombosis, any pulmonary embolism, and VTE-related death – was 1.2% in patients treated with semuloparin vs. 3.4% in a control group treated with placebo (hazard ratio, 0.36; P less than .0001).

Benefits trended in favor of semuloparin for all components of the composite end point, including any pulmonary embolism (odds ratio, 0.41) and VTE-related death (OR, 0.77), reported Dr. Daniel J. George, who presented the paper on behalf of Dr. Giancarlo Agnelli of Perugia (Italy) University at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of clinically relevant bleeding was higher at 2.8% with semuloparin vs. 2% for placebo, Dr. George added that a safety analysis found that the incidence of major bleeding was similarly low, at 1.2% and 1.1%, respectively.

Based on the trial results, Dr. Elias Zerhouni, president of global research and development at trial sponsor Sanofi-Aventis, announced that the company plans "to submit semuloparin for regulatory filing" in the third quarter of 2011. Still investigational, the selectively engineered anticoagulant has high anti–coagulation factor Xa activity and minimal anti–coagulation factor IIa activity with a half-life of 16-20 hours.

Although it is advocated for cancer patients who are hospitalized or undergoing surgery and is not contraindicated for anticoagulation, the routine prophylaxis of ambulatory cancer patients receiving chemotherapy is not currently recommended.

"So this leaves us with the question, Which cancer patients should we now consider for thromboprophylaxis?" said Dr. George of Duke University Medical Center in Durham, N.C. "Already our guidelines suggest that those patients with cancer undergoing major surgery, or hospitalized, or acutely ill, ought to be anticoagulated with low-molecular-weight heparin during those periods of time.

"I would now submit that the SAVE ONCO data would support having patients initiating chemotherapy, in the setting of locally advanced or metastatic disease, as a third population that we could consider for thromboprophylaxis," he said.

Although discussant Dr. Vered Stearns of Johns Hopkins University in Baltimore viewed the findings favorably, she cautioned that "SAVE-ONCO should not change current practice for the overall population."

Dr. Stearns emphasized that predictive models are needed to determine which ambulatory patients are at the highest risk for VTE, "and who should be offered prophylaxis in the context of expected clinical outcomes." Biomarkers such as circulating coagulating factors are also important, she added.

"Semuloparin is an efficacious and safe agent. That’s very exciting," Dr. Stearns said. "The reduction in [VTE] events is consistent throughout the report, and my understanding is [that] the group is conducting subgroup analysis and evaluation of predictive markers that may help us select the population that would benefit from primary prophylaxis."

A multinational study, the SAVE-ONCO trial enrolled 3,200 patients who were at high risk of VTE. Participants had metastatic or locally advanced solid tumors such as lung, pancreas, stomach, colon/rectal, bladder, or ovarian tumors for which they were starting a new course of chemotherapy with minimum treatment intent of 3 months.

Patients were randomized 1:1 to standard-care chemotherapy plus either placebo or semuloparin 20 mg subcutaneously once daily for the length of their chemotherapy.

Patient characteristics were well balanced across both arms: The median age was 60 years, and 60% of patients were men. More than two-thirds had metastatic disease. Lung cancer was the most common tumor type (36%) followed by colon/rectal cancer (28%). The remainder had cancer of the stomach, ovary, pancreas, or bladder. Treatment duration was approximately 3.5 months in both groups.

In response to audience questions, Dr. George said that the study did not show a survival benefit, but "there is likely a subset of patients" for whom this made a dramatic impact in their early morbidity and mortality.

The study did not address cost, but that will be a factor if prophylaxis is introduced for a large population of cancer patients, he acknowledged, "It really comes down to safety and cost," he said.

The study was sponsored by Sanofi-Aventis. Dr. George disclosed numerous relationships with pharmaceutical companies, including consultant or advisory role, honoraria, and speakers bureau with Sanofi-Aventis. Dr. Agnelli disclosed receiving honoraria from Sanofi-Aventis and relationships with other companies. Dr. Stearns disclosed honoraria and research funding from other companies.

CHICAGO – Prophylaxis with semuloparin, an experimental ultralow-molecular-weight heparin, achieved a significant 64% reduction in relative risk for venous thromboembolism events among cancer patients undergoing chemotherapy in a large, randomized, double-blind, phase III trial called SAVE-ONCO.

An intent-to-treat analysis found that the rate of venous thromboembolism (VTE) events – a composite of symptomatic deep vein thrombosis, any pulmonary embolism, and VTE-related death – was 1.2% in patients treated with semuloparin vs. 3.4% in a control group treated with placebo (hazard ratio, 0.36; P less than .0001).

Benefits trended in favor of semuloparin for all components of the composite end point, including any pulmonary embolism (odds ratio, 0.41) and VTE-related death (OR, 0.77), reported Dr. Daniel J. George, who presented the paper on behalf of Dr. Giancarlo Agnelli of Perugia (Italy) University at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of clinically relevant bleeding was higher at 2.8% with semuloparin vs. 2% for placebo, Dr. George added that a safety analysis found that the incidence of major bleeding was similarly low, at 1.2% and 1.1%, respectively.

Based on the trial results, Dr. Elias Zerhouni, president of global research and development at trial sponsor Sanofi-Aventis, announced that the company plans "to submit semuloparin for regulatory filing" in the third quarter of 2011. Still investigational, the selectively engineered anticoagulant has high anti–coagulation factor Xa activity and minimal anti–coagulation factor IIa activity with a half-life of 16-20 hours.

Although it is advocated for cancer patients who are hospitalized or undergoing surgery and is not contraindicated for anticoagulation, the routine prophylaxis of ambulatory cancer patients receiving chemotherapy is not currently recommended.

"So this leaves us with the question, Which cancer patients should we now consider for thromboprophylaxis?" said Dr. George of Duke University Medical Center in Durham, N.C. "Already our guidelines suggest that those patients with cancer undergoing major surgery, or hospitalized, or acutely ill, ought to be anticoagulated with low-molecular-weight heparin during those periods of time.

"I would now submit that the SAVE ONCO data would support having patients initiating chemotherapy, in the setting of locally advanced or metastatic disease, as a third population that we could consider for thromboprophylaxis," he said.

Although discussant Dr. Vered Stearns of Johns Hopkins University in Baltimore viewed the findings favorably, she cautioned that "SAVE-ONCO should not change current practice for the overall population."

Dr. Stearns emphasized that predictive models are needed to determine which ambulatory patients are at the highest risk for VTE, "and who should be offered prophylaxis in the context of expected clinical outcomes." Biomarkers such as circulating coagulating factors are also important, she added.

"Semuloparin is an efficacious and safe agent. That’s very exciting," Dr. Stearns said. "The reduction in [VTE] events is consistent throughout the report, and my understanding is [that] the group is conducting subgroup analysis and evaluation of predictive markers that may help us select the population that would benefit from primary prophylaxis."

A multinational study, the SAVE-ONCO trial enrolled 3,200 patients who were at high risk of VTE. Participants had metastatic or locally advanced solid tumors such as lung, pancreas, stomach, colon/rectal, bladder, or ovarian tumors for which they were starting a new course of chemotherapy with minimum treatment intent of 3 months.

Patients were randomized 1:1 to standard-care chemotherapy plus either placebo or semuloparin 20 mg subcutaneously once daily for the length of their chemotherapy.

Patient characteristics were well balanced across both arms: The median age was 60 years, and 60% of patients were men. More than two-thirds had metastatic disease. Lung cancer was the most common tumor type (36%) followed by colon/rectal cancer (28%). The remainder had cancer of the stomach, ovary, pancreas, or bladder. Treatment duration was approximately 3.5 months in both groups.

In response to audience questions, Dr. George said that the study did not show a survival benefit, but "there is likely a subset of patients" for whom this made a dramatic impact in their early morbidity and mortality.

The study did not address cost, but that will be a factor if prophylaxis is introduced for a large population of cancer patients, he acknowledged, "It really comes down to safety and cost," he said.

The study was sponsored by Sanofi-Aventis. Dr. George disclosed numerous relationships with pharmaceutical companies, including consultant or advisory role, honoraria, and speakers bureau with Sanofi-Aventis. Dr. Agnelli disclosed receiving honoraria from Sanofi-Aventis and relationships with other companies. Dr. Stearns disclosed honoraria and research funding from other companies.

CHICAGO – Prophylaxis with semuloparin, an experimental ultralow-molecular-weight heparin, achieved a significant 64% reduction in relative risk for venous thromboembolism events among cancer patients undergoing chemotherapy in a large, randomized, double-blind, phase III trial called SAVE-ONCO.

An intent-to-treat analysis found that the rate of venous thromboembolism (VTE) events – a composite of symptomatic deep vein thrombosis, any pulmonary embolism, and VTE-related death – was 1.2% in patients treated with semuloparin vs. 3.4% in a control group treated with placebo (hazard ratio, 0.36; P less than .0001).

Benefits trended in favor of semuloparin for all components of the composite end point, including any pulmonary embolism (odds ratio, 0.41) and VTE-related death (OR, 0.77), reported Dr. Daniel J. George, who presented the paper on behalf of Dr. Giancarlo Agnelli of Perugia (Italy) University at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of clinically relevant bleeding was higher at 2.8% with semuloparin vs. 2% for placebo, Dr. George added that a safety analysis found that the incidence of major bleeding was similarly low, at 1.2% and 1.1%, respectively.

Based on the trial results, Dr. Elias Zerhouni, president of global research and development at trial sponsor Sanofi-Aventis, announced that the company plans "to submit semuloparin for regulatory filing" in the third quarter of 2011. Still investigational, the selectively engineered anticoagulant has high anti–coagulation factor Xa activity and minimal anti–coagulation factor IIa activity with a half-life of 16-20 hours.

Although it is advocated for cancer patients who are hospitalized or undergoing surgery and is not contraindicated for anticoagulation, the routine prophylaxis of ambulatory cancer patients receiving chemotherapy is not currently recommended.

"So this leaves us with the question, Which cancer patients should we now consider for thromboprophylaxis?" said Dr. George of Duke University Medical Center in Durham, N.C. "Already our guidelines suggest that those patients with cancer undergoing major surgery, or hospitalized, or acutely ill, ought to be anticoagulated with low-molecular-weight heparin during those periods of time.

"I would now submit that the SAVE ONCO data would support having patients initiating chemotherapy, in the setting of locally advanced or metastatic disease, as a third population that we could consider for thromboprophylaxis," he said.

Although discussant Dr. Vered Stearns of Johns Hopkins University in Baltimore viewed the findings favorably, she cautioned that "SAVE-ONCO should not change current practice for the overall population."

Dr. Stearns emphasized that predictive models are needed to determine which ambulatory patients are at the highest risk for VTE, "and who should be offered prophylaxis in the context of expected clinical outcomes." Biomarkers such as circulating coagulating factors are also important, she added.

"Semuloparin is an efficacious and safe agent. That’s very exciting," Dr. Stearns said. "The reduction in [VTE] events is consistent throughout the report, and my understanding is [that] the group is conducting subgroup analysis and evaluation of predictive markers that may help us select the population that would benefit from primary prophylaxis."

A multinational study, the SAVE-ONCO trial enrolled 3,200 patients who were at high risk of VTE. Participants had metastatic or locally advanced solid tumors such as lung, pancreas, stomach, colon/rectal, bladder, or ovarian tumors for which they were starting a new course of chemotherapy with minimum treatment intent of 3 months.

Patients were randomized 1:1 to standard-care chemotherapy plus either placebo or semuloparin 20 mg subcutaneously once daily for the length of their chemotherapy.

Patient characteristics were well balanced across both arms: The median age was 60 years, and 60% of patients were men. More than two-thirds had metastatic disease. Lung cancer was the most common tumor type (36%) followed by colon/rectal cancer (28%). The remainder had cancer of the stomach, ovary, pancreas, or bladder. Treatment duration was approximately 3.5 months in both groups.

In response to audience questions, Dr. George said that the study did not show a survival benefit, but "there is likely a subset of patients" for whom this made a dramatic impact in their early morbidity and mortality.

The study did not address cost, but that will be a factor if prophylaxis is introduced for a large population of cancer patients, he acknowledged, "It really comes down to safety and cost," he said.

The study was sponsored by Sanofi-Aventis. Dr. George disclosed numerous relationships with pharmaceutical companies, including consultant or advisory role, honoraria, and speakers bureau with Sanofi-Aventis. Dr. Agnelli disclosed receiving honoraria from Sanofi-Aventis and relationships with other companies. Dr. Stearns disclosed honoraria and research funding from other companies.

CHICAGO – Prophylaxis with semuloparin, an experimental ultralow-molecular-weight heparin, achieved a significant 64% reduction in relative risk for venous thromboembolism events among cancer patients undergoing chemotherapy in a large, randomized, double-blind, phase III trial called SAVE-ONCO.

An intent-to-treat analysis found that the rate of venous thromboembolism (VTE) events – a composite of symptomatic deep vein thrombosis, any pulmonary embolism, and VTE-related death – was 1.2% in patients treated with semuloparin vs. 3.4% in a control group treated with placebo (hazard ratio, 0.36; P less than .0001).

Benefits trended in favor of semuloparin for all components of the composite end point, including any pulmonary embolism (odds ratio, 0.41) and VTE-related death (OR, 0.77), reported Dr. Daniel J. George, who presented the paper on behalf of Dr. Giancarlo Agnelli of Perugia (Italy) University at the annual meeting of the American Society of Clinical Oncology.

Although the incidence of clinically relevant bleeding was higher at 2.8% with semuloparin vs. 2% for placebo, Dr. George added that a safety analysis found that the incidence of major bleeding was similarly low, at 1.2% and 1.1%, respectively.

Based on the trial results, Dr. Elias Zerhouni, president of global research and development at trial sponsor Sanofi-Aventis, announced that the company plans "to submit semuloparin for regulatory filing" in the third quarter of 2011. Still investigational, the selectively engineered anticoagulant has high anti–coagulation factor Xa activity and minimal anti–coagulation factor IIa activity with a half-life of 16-20 hours.

Although it is advocated for cancer patients who are hospitalized or undergoing surgery and is not contraindicated for anticoagulation, the routine prophylaxis of ambulatory cancer patients receiving chemotherapy is not currently recommended.

"So this leaves us with the question, Which cancer patients should we now consider for thromboprophylaxis?" said Dr. George of Duke University Medical Center in Durham, N.C. "Already our guidelines suggest that those patients with cancer undergoing major surgery, or hospitalized, or acutely ill, ought to be anticoagulated with low-molecular-weight heparin during those periods of time.

"I would now submit that the SAVE ONCO data would support having patients initiating chemotherapy, in the setting of locally advanced or metastatic disease, as a third population that we could consider for thromboprophylaxis," he said.

Although discussant Dr. Vered Stearns of Johns Hopkins University in Baltimore viewed the findings favorably, she cautioned that "SAVE-ONCO should not change current practice for the overall population."

Dr. Stearns emphasized that predictive models are needed to determine which ambulatory patients are at the highest risk for VTE, "and who should be offered prophylaxis in the context of expected clinical outcomes." Biomarkers such as circulating coagulating factors are also important, she added.

"Semuloparin is an efficacious and safe agent. That’s very exciting," Dr. Stearns said. "The reduction in [VTE] events is consistent throughout the report, and my understanding is [that] the group is conducting subgroup analysis and evaluation of predictive markers that may help us select the population that would benefit from primary prophylaxis."

A multinational study, the SAVE-ONCO trial enrolled 3,200 patients who were at high risk of VTE. Participants had metastatic or locally advanced solid tumors such as lung, pancreas, stomach, colon/rectal, bladder, or ovarian tumors for which they were starting a new course of chemotherapy with minimum treatment intent of 3 months.

Patients were randomized 1:1 to standard-care chemotherapy plus either placebo or semuloparin 20 mg subcutaneously once daily for the length of their chemotherapy.

Patient characteristics were well balanced across both arms: The median age was 60 years, and 60% of patients were men. More than two-thirds had metastatic disease. Lung cancer was the most common tumor type (36%) followed by colon/rectal cancer (28%). The remainder had cancer of the stomach, ovary, pancreas, or bladder. Treatment duration was approximately 3.5 months in both groups.

In response to audience questions, Dr. George said that the study did not show a survival benefit, but "there is likely a subset of patients" for whom this made a dramatic impact in their early morbidity and mortality.

The study did not address cost, but that will be a factor if prophylaxis is introduced for a large population of cancer patients, he acknowledged, "It really comes down to safety and cost," he said.

The study was sponsored by Sanofi-Aventis. Dr. George disclosed numerous relationships with pharmaceutical companies, including consultant or advisory role, honoraria, and speakers bureau with Sanofi-Aventis. Dr. Agnelli disclosed receiving honoraria from Sanofi-Aventis and relationships with other companies. Dr. Stearns disclosed honoraria and research funding from other companies.