EHA Congress 2012

AMSTERDAM  – Ask a hematologist about the most serious quality of life issues for patients with multiple myeloma, and neuropathy typically tops the list. But fatigue, malaise, or muscle weakness was more often concerning to patients who answered a survey on treatment-related side effects.

Cancer patients and their physicians differ to a large extent in their perceptions of a treatment’s impact on quality of life, according to Eric Low, the founder and chief executive of Myeloma UK. Even caregivers with a clear view of day-to-day realities may not see the patients’ point of view.

Although the patients’ caregivers "will often have a more accurate insight into how the cancer is affecting patients than the patients themselves, patients put more emphasis on quality than on longevity of life," he observed, citing data from the United Kingdom and from Europe, with myeloma patients specifically.

Contradictions in how patients and practitioners perceive quality of life was a recurrent theme in talks by patient advocates at the recent annual congress of the European Hematology Association. They described efforts to give patients a stronger voice through Internet-based questionnaires, physician guidelines, and tools for quality of life (QoL) assessment.

"There is such a large difference in perception of quality of life and what doctors think of quality of life in practice of a therapy and symptoms of disease, and what patients perceive about their impact on quality of life and symptoms," said Jan Geissler, a cofounder of the CML [Chronic Myeloid Leukemia] Advocates Network and director of the EUPATI (European Patients’ Academy on Therapeutic Innovation).

For patients on therapy, the need "is not only survival, but includes a lot of factors including quality of life – including, let’s say, how to cope with the disease, psychological factors," added Mr. Geissler, a CML survivor.

Survey Pinpoints Discrepancies

In 2009, Myeloma Euronet – which recently changed its name to Myeloma Patients Europe – conducted a survey to look at the effects of treatment side effects and unmet patient needs in patients with multiple myeloma. The aim was to look at, and compare, the opinions of those affected by the disease, including family members and general caregivers, vs. those of the medical profession.

A total of 314 health care professionals – among them 217 hematologists, 15 medical oncologists, 8 hematologist-oncologists, 68 nurses, and 5 other professionals – from 43 countries took part.

Participants also included 173 patients with multiple myeloma from 17 countries, and 85 relatives and 2 caregivers participating on behalf of myeloma patients from 13 countries. The largest patient contingent came from Poland.

The findings were enlightening, Mr. Low said. Patients and health care providers viewed the potential negative impact of several treatment-related side effects on overall well-being very differently.

Among physicians and nurses (83% and 77%, respectively), neuropathy was most often cited as having a negative impact on a patients’ well-being.

This was followed by a broad category of fatigue/malaise/weakness/dizziness/somnolence/sedation/insomnia, which was cited more often by nurses (72%) than by physicians (60%).

For physicians, infection had the third most negative impact. It was cited by (56%), followed by pain (48%) and thrombotic events (47%). A majority (62%) of nurses put nausea and vomiting in the No. 3 spot, however, followed by pain (57%). Infections and effects on the stomach and/or colon were each cited by 47% of nurses.

Among patients, relatives, and caregivers, the treatment side effect most often cited as compromising daily life fell into the broad category of fatigue/malaise/weakness/dizziness/somnolence/sedation/insomnia. This was cited by 73% of patients and 70% of their relatives and caregivers.

Neuropathy ranked second in negative impact for patients (54%) but was cited less often (45%) by relatives and caregivers, who put effects on the stomach and/or colon in second place (55%). Whereas decreased body function followed as No. 3 in negative impact among patients (53%), hair loss was cited by 52% of relatives and caregivers.

There were also several treatment-related side effects that patients did not report to their doctor, perhaps because they felt uncomfortable to do so. These included sexual problems, diarrhea, constipation, gastrointestinal upsets, and psychological issues, among others.

"Patients often put on a brave face, don’t want to let the side down, and associate [having] a positive outlook with therapeutic benefit," observed Mr. Low.

Moreover, balancing efficacy against side effects is "not what drives the patient all the time," he said. What patients want from treatment is very individual; although some patients may want greater choice or involvement in making decisions about their care, others may not. Some may prefer convenience or fewer side effects; others may want maximum disease control and a long, durable remission.

"It’s important that doctors tweak out what the objectives are for each individual patient and try to facilitate these in terms of how they are managed, and what treatments options are available," Mr. Low said. Quality of life should be considered as much as clinical outcomes, he suggested.

RareConnect Gathers Patient-Reported Information

An initiative called RareConnect could help provide important information about the effects of treatment from the patient perspective. Run by the EURODIS (European Organization for Rare Diseases), and by the U.S.-based NORD (National Organization for Rare Disorders), RareConnect is a social network of rare-disease communities that offers users the opportunity to assess patient-reported quality of life via a series of Internet-based questionnaires.

"What we are trying to do is bring a certain sense of structure now to the way patients can report on outcomes, essentially," said Denis Costello, who is leading the RareConnect project on behalf of EURODIS.

A pilot project is underway in patients with myeloma, he added in an interview. The Internet-based tool involves a series of interactive questionnaires that patients answer at a minimum of once a week. The collected information will include when patients were diagnosed, what treatments they have used, and their sliding-scale ratings of any side effects they have experienced.

RareConnect also allows patients to see how they compare with the rest of the community, and they can discuss their condition with others who are in a similar situation.

To develop a patient-friendly tool with the right level of lightness has been challenging because physicians want it to follow the lines of the quality of life scales and currently available instruments, Mr. Costello said. Physicians "want to get statistically significant data, but patients, we know, are not going to fill in those kinds of questionnaires."

Ultimately, "we want to provide a tool to patients to help them better self-manage their own outcomes in conjunction with their [health care professional], because we feel that this tool can help the patient, and bring a new dynamism between patient and doctor," he explained.

"It’s about discussion, really," Mr. Costello added, noting that the tool could help patients be more aware of their treatment and how it may affect them. In myeloma, for example, it could help prevent patients’ stopping treatment too early and later suffering a relapse.

"We really want to empower patients to see that [perhaps] you need to stay on the treatment a bit longer, and sometimes you need to fight," he suggested. RareConnect and other similar initiatives could provide the starting evidence that patients need to discuss such issues with their doctor.

Measuring Quality of Life

The European Hematology Association’s Scientific Working Group on Quality of Life and Symptoms has just published guidelines on how to assess quality of life in patients with hematologic disorders. Aimed at the practicing hematologist, these guidelines cover hematological malignancies, as well as other blood conditions.

"As physicians, as researchers, we understand that we do have new treatment modalities; we are able to provide good quality of care, but it very important to have the patient perspective to know if we are doing everything in the right way," said Tatyana Ionova, Ph.D., professor of the Postgraduate Education Institute at the National Medical Surgical Center Northwestern Branch in St. Petersburg, Russian Federation.

"Sometimes we may have information about the success or benefit or risks of treatment only from the patient perspective. That is why we try to develop the instruments, [which are] standardized measures that are able to ask the patients about their physical, social, psychological well-being, about [their] symptoms," Dr. Ionova said.

The EHA guidelines on "Patient-Reported Outcomes in Hematology" recognize that there are differences between hematologic diseases in terms of the quality of life assessments that can be used, "because bone marrow transplantation is very different from ITP [immune thrombocytopenic purpura," Dr. Ionova noted.

So how should hematologists measure quality of life? "First, read the guidelines," she suggested. "Then, have some very simple training about the questionnaires and how to use them."

These questionnaires shouldn’t take very long to be completed by or with the patient, she added. The important thing is that quality of life is considered.

The Myeloma Euronet survey was made possible through an unrestricted grant from Ortho Biotech. All authors reported no relevant disclosures other than working for their respective organizations.

AMSTERDAM  – Ask a hematologist about the most serious quality of life issues for patients with multiple myeloma, and neuropathy typically tops the list. But fatigue, malaise, or muscle weakness was more often concerning to patients who answered a survey on treatment-related side effects.

Cancer patients and their physicians differ to a large extent in their perceptions of a treatment’s impact on quality of life, according to Eric Low, the founder and chief executive of Myeloma UK. Even caregivers with a clear view of day-to-day realities may not see the patients’ point of view.

Although the patients’ caregivers "will often have a more accurate insight into how the cancer is affecting patients than the patients themselves, patients put more emphasis on quality than on longevity of life," he observed, citing data from the United Kingdom and from Europe, with myeloma patients specifically.

Contradictions in how patients and practitioners perceive quality of life was a recurrent theme in talks by patient advocates at the recent annual congress of the European Hematology Association. They described efforts to give patients a stronger voice through Internet-based questionnaires, physician guidelines, and tools for quality of life (QoL) assessment.

"There is such a large difference in perception of quality of life and what doctors think of quality of life in practice of a therapy and symptoms of disease, and what patients perceive about their impact on quality of life and symptoms," said Jan Geissler, a cofounder of the CML [Chronic Myeloid Leukemia] Advocates Network and director of the EUPATI (European Patients’ Academy on Therapeutic Innovation).

For patients on therapy, the need "is not only survival, but includes a lot of factors including quality of life – including, let’s say, how to cope with the disease, psychological factors," added Mr. Geissler, a CML survivor.

Survey Pinpoints Discrepancies

In 2009, Myeloma Euronet – which recently changed its name to Myeloma Patients Europe – conducted a survey to look at the effects of treatment side effects and unmet patient needs in patients with multiple myeloma. The aim was to look at, and compare, the opinions of those affected by the disease, including family members and general caregivers, vs. those of the medical profession.

A total of 314 health care professionals – among them 217 hematologists, 15 medical oncologists, 8 hematologist-oncologists, 68 nurses, and 5 other professionals – from 43 countries took part.

Participants also included 173 patients with multiple myeloma from 17 countries, and 85 relatives and 2 caregivers participating on behalf of myeloma patients from 13 countries. The largest patient contingent came from Poland.

The findings were enlightening, Mr. Low said. Patients and health care providers viewed the potential negative impact of several treatment-related side effects on overall well-being very differently.

Among physicians and nurses (83% and 77%, respectively), neuropathy was most often cited as having a negative impact on a patients’ well-being.

This was followed by a broad category of fatigue/malaise/weakness/dizziness/somnolence/sedation/insomnia, which was cited more often by nurses (72%) than by physicians (60%).

For physicians, infection had the third most negative impact. It was cited by (56%), followed by pain (48%) and thrombotic events (47%). A majority (62%) of nurses put nausea and vomiting in the No. 3 spot, however, followed by pain (57%). Infections and effects on the stomach and/or colon were each cited by 47% of nurses.

Among patients, relatives, and caregivers, the treatment side effect most often cited as compromising daily life fell into the broad category of fatigue/malaise/weakness/dizziness/somnolence/sedation/insomnia. This was cited by 73% of patients and 70% of their relatives and caregivers.

Neuropathy ranked second in negative impact for patients (54%) but was cited less often (45%) by relatives and caregivers, who put effects on the stomach and/or colon in second place (55%). Whereas decreased body function followed as No. 3 in negative impact among patients (53%), hair loss was cited by 52% of relatives and caregivers.

There were also several treatment-related side effects that patients did not report to their doctor, perhaps because they felt uncomfortable to do so. These included sexual problems, diarrhea, constipation, gastrointestinal upsets, and psychological issues, among others.

"Patients often put on a brave face, don’t want to let the side down, and associate [having] a positive outlook with therapeutic benefit," observed Mr. Low.

Moreover, balancing efficacy against side effects is "not what drives the patient all the time," he said. What patients want from treatment is very individual; although some patients may want greater choice or involvement in making decisions about their care, others may not. Some may prefer convenience or fewer side effects; others may want maximum disease control and a long, durable remission.

"It’s important that doctors tweak out what the objectives are for each individual patient and try to facilitate these in terms of how they are managed, and what treatments options are available," Mr. Low said. Quality of life should be considered as much as clinical outcomes, he suggested.

RareConnect Gathers Patient-Reported Information

An initiative called RareConnect could help provide important information about the effects of treatment from the patient perspective. Run by the EURODIS (European Organization for Rare Diseases), and by the U.S.-based NORD (National Organization for Rare Disorders), RareConnect is a social network of rare-disease communities that offers users the opportunity to assess patient-reported quality of life via a series of Internet-based questionnaires.

"What we are trying to do is bring a certain sense of structure now to the way patients can report on outcomes, essentially," said Denis Costello, who is leading the RareConnect project on behalf of EURODIS.

A pilot project is underway in patients with myeloma, he added in an interview. The Internet-based tool involves a series of interactive questionnaires that patients answer at a minimum of once a week. The collected information will include when patients were diagnosed, what treatments they have used, and their sliding-scale ratings of any side effects they have experienced.

RareConnect also allows patients to see how they compare with the rest of the community, and they can discuss their condition with others who are in a similar situation.

To develop a patient-friendly tool with the right level of lightness has been challenging because physicians want it to follow the lines of the quality of life scales and currently available instruments, Mr. Costello said. Physicians "want to get statistically significant data, but patients, we know, are not going to fill in those kinds of questionnaires."

Ultimately, "we want to provide a tool to patients to help them better self-manage their own outcomes in conjunction with their [health care professional], because we feel that this tool can help the patient, and bring a new dynamism between patient and doctor," he explained.

"It’s about discussion, really," Mr. Costello added, noting that the tool could help patients be more aware of their treatment and how it may affect them. In myeloma, for example, it could help prevent patients’ stopping treatment too early and later suffering a relapse.

"We really want to empower patients to see that [perhaps] you need to stay on the treatment a bit longer, and sometimes you need to fight," he suggested. RareConnect and other similar initiatives could provide the starting evidence that patients need to discuss such issues with their doctor.

Measuring Quality of Life

The European Hematology Association’s Scientific Working Group on Quality of Life and Symptoms has just published guidelines on how to assess quality of life in patients with hematologic disorders. Aimed at the practicing hematologist, these guidelines cover hematological malignancies, as well as other blood conditions.

"As physicians, as researchers, we understand that we do have new treatment modalities; we are able to provide good quality of care, but it very important to have the patient perspective to know if we are doing everything in the right way," said Tatyana Ionova, Ph.D., professor of the Postgraduate Education Institute at the National Medical Surgical Center Northwestern Branch in St. Petersburg, Russian Federation.

"Sometimes we may have information about the success or benefit or risks of treatment only from the patient perspective. That is why we try to develop the instruments, [which are] standardized measures that are able to ask the patients about their physical, social, psychological well-being, about [their] symptoms," Dr. Ionova said.

The EHA guidelines on "Patient-Reported Outcomes in Hematology" recognize that there are differences between hematologic diseases in terms of the quality of life assessments that can be used, "because bone marrow transplantation is very different from ITP [immune thrombocytopenic purpura," Dr. Ionova noted.

So how should hematologists measure quality of life? "First, read the guidelines," she suggested. "Then, have some very simple training about the questionnaires and how to use them."

These questionnaires shouldn’t take very long to be completed by or with the patient, she added. The important thing is that quality of life is considered.

The Myeloma Euronet survey was made possible through an unrestricted grant from Ortho Biotech. All authors reported no relevant disclosures other than working for their respective organizations.

AMSTERDAM  – Ask a hematologist about the most serious quality of life issues for patients with multiple myeloma, and neuropathy typically tops the list. But fatigue, malaise, or muscle weakness was more often concerning to patients who answered a survey on treatment-related side effects.

Cancer patients and their physicians differ to a large extent in their perceptions of a treatment’s impact on quality of life, according to Eric Low, the founder and chief executive of Myeloma UK. Even caregivers with a clear view of day-to-day realities may not see the patients’ point of view.

Although the patients’ caregivers "will often have a more accurate insight into how the cancer is affecting patients than the patients themselves, patients put more emphasis on quality than on longevity of life," he observed, citing data from the United Kingdom and from Europe, with myeloma patients specifically.

Contradictions in how patients and practitioners perceive quality of life was a recurrent theme in talks by patient advocates at the recent annual congress of the European Hematology Association. They described efforts to give patients a stronger voice through Internet-based questionnaires, physician guidelines, and tools for quality of life (QoL) assessment.

"There is such a large difference in perception of quality of life and what doctors think of quality of life in practice of a therapy and symptoms of disease, and what patients perceive about their impact on quality of life and symptoms," said Jan Geissler, a cofounder of the CML [Chronic Myeloid Leukemia] Advocates Network and director of the EUPATI (European Patients’ Academy on Therapeutic Innovation).

For patients on therapy, the need "is not only survival, but includes a lot of factors including quality of life – including, let’s say, how to cope with the disease, psychological factors," added Mr. Geissler, a CML survivor.

Survey Pinpoints Discrepancies

In 2009, Myeloma Euronet – which recently changed its name to Myeloma Patients Europe – conducted a survey to look at the effects of treatment side effects and unmet patient needs in patients with multiple myeloma. The aim was to look at, and compare, the opinions of those affected by the disease, including family members and general caregivers, vs. those of the medical profession.

A total of 314 health care professionals – among them 217 hematologists, 15 medical oncologists, 8 hematologist-oncologists, 68 nurses, and 5 other professionals – from 43 countries took part.

Participants also included 173 patients with multiple myeloma from 17 countries, and 85 relatives and 2 caregivers participating on behalf of myeloma patients from 13 countries. The largest patient contingent came from Poland.

The findings were enlightening, Mr. Low said. Patients and health care providers viewed the potential negative impact of several treatment-related side effects on overall well-being very differently.

Among physicians and nurses (83% and 77%, respectively), neuropathy was most often cited as having a negative impact on a patients’ well-being.

This was followed by a broad category of fatigue/malaise/weakness/dizziness/somnolence/sedation/insomnia, which was cited more often by nurses (72%) than by physicians (60%).

For physicians, infection had the third most negative impact. It was cited by (56%), followed by pain (48%) and thrombotic events (47%). A majority (62%) of nurses put nausea and vomiting in the No. 3 spot, however, followed by pain (57%). Infections and effects on the stomach and/or colon were each cited by 47% of nurses.

Among patients, relatives, and caregivers, the treatment side effect most often cited as compromising daily life fell into the broad category of fatigue/malaise/weakness/dizziness/somnolence/sedation/insomnia. This was cited by 73% of patients and 70% of their relatives and caregivers.

Neuropathy ranked second in negative impact for patients (54%) but was cited less often (45%) by relatives and caregivers, who put effects on the stomach and/or colon in second place (55%). Whereas decreased body function followed as No. 3 in negative impact among patients (53%), hair loss was cited by 52% of relatives and caregivers.

There were also several treatment-related side effects that patients did not report to their doctor, perhaps because they felt uncomfortable to do so. These included sexual problems, diarrhea, constipation, gastrointestinal upsets, and psychological issues, among others.

"Patients often put on a brave face, don’t want to let the side down, and associate [having] a positive outlook with therapeutic benefit," observed Mr. Low.

Moreover, balancing efficacy against side effects is "not what drives the patient all the time," he said. What patients want from treatment is very individual; although some patients may want greater choice or involvement in making decisions about their care, others may not. Some may prefer convenience or fewer side effects; others may want maximum disease control and a long, durable remission.

"It’s important that doctors tweak out what the objectives are for each individual patient and try to facilitate these in terms of how they are managed, and what treatments options are available," Mr. Low said. Quality of life should be considered as much as clinical outcomes, he suggested.

RareConnect Gathers Patient-Reported Information

An initiative called RareConnect could help provide important information about the effects of treatment from the patient perspective. Run by the EURODIS (European Organization for Rare Diseases), and by the U.S.-based NORD (National Organization for Rare Disorders), RareConnect is a social network of rare-disease communities that offers users the opportunity to assess patient-reported quality of life via a series of Internet-based questionnaires.

"What we are trying to do is bring a certain sense of structure now to the way patients can report on outcomes, essentially," said Denis Costello, who is leading the RareConnect project on behalf of EURODIS.

A pilot project is underway in patients with myeloma, he added in an interview. The Internet-based tool involves a series of interactive questionnaires that patients answer at a minimum of once a week. The collected information will include when patients were diagnosed, what treatments they have used, and their sliding-scale ratings of any side effects they have experienced.

RareConnect also allows patients to see how they compare with the rest of the community, and they can discuss their condition with others who are in a similar situation.

To develop a patient-friendly tool with the right level of lightness has been challenging because physicians want it to follow the lines of the quality of life scales and currently available instruments, Mr. Costello said. Physicians "want to get statistically significant data, but patients, we know, are not going to fill in those kinds of questionnaires."

Ultimately, "we want to provide a tool to patients to help them better self-manage their own outcomes in conjunction with their [health care professional], because we feel that this tool can help the patient, and bring a new dynamism between patient and doctor," he explained.

"It’s about discussion, really," Mr. Costello added, noting that the tool could help patients be more aware of their treatment and how it may affect them. In myeloma, for example, it could help prevent patients’ stopping treatment too early and later suffering a relapse.

"We really want to empower patients to see that [perhaps] you need to stay on the treatment a bit longer, and sometimes you need to fight," he suggested. RareConnect and other similar initiatives could provide the starting evidence that patients need to discuss such issues with their doctor.

Measuring Quality of Life

The European Hematology Association’s Scientific Working Group on Quality of Life and Symptoms has just published guidelines on how to assess quality of life in patients with hematologic disorders. Aimed at the practicing hematologist, these guidelines cover hematological malignancies, as well as other blood conditions.

"As physicians, as researchers, we understand that we do have new treatment modalities; we are able to provide good quality of care, but it very important to have the patient perspective to know if we are doing everything in the right way," said Tatyana Ionova, Ph.D., professor of the Postgraduate Education Institute at the National Medical Surgical Center Northwestern Branch in St. Petersburg, Russian Federation.

"Sometimes we may have information about the success or benefit or risks of treatment only from the patient perspective. That is why we try to develop the instruments, [which are] standardized measures that are able to ask the patients about their physical, social, psychological well-being, about [their] symptoms," Dr. Ionova said.

The EHA guidelines on "Patient-Reported Outcomes in Hematology" recognize that there are differences between hematologic diseases in terms of the quality of life assessments that can be used, "because bone marrow transplantation is very different from ITP [immune thrombocytopenic purpura," Dr. Ionova noted.

So how should hematologists measure quality of life? "First, read the guidelines," she suggested. "Then, have some very simple training about the questionnaires and how to use them."

These questionnaires shouldn’t take very long to be completed by or with the patient, she added. The important thing is that quality of life is considered.

The Myeloma Euronet survey was made possible through an unrestricted grant from Ortho Biotech. All authors reported no relevant disclosures other than working for their respective organizations.

AMSTERDAM – Measuring BCR-ABL transcript levels at 3 and 6 months can predict the outcome of treatment with nilotinib in patients newly diagnosed with chronic myeloid leukemia, according to new data from the ENESTnd study.

Patients with lower levels at these milestones had higher rates of progression-free and overall survival, whether they received nilotinib (Tasigna) or imatinib (Gleevec) in the pivotal phase III study, investigators reported at the annual congress of the European Hematology Association (EHA).

"The main message is that for patients who are on imatinib, you have an early predictor of response that you may use the second-generation drugs if there is a problem – and the same now applies for second-generation drugs," the lead author Dr. Andreas Hochhaus, said in an interview.

The phase III ENESTnd [Evaluating Nilotinib Efficacy and Safety in Clinical Trials Newly Diagnosed Ph+ CML Patients] trial led to the approval of nilotinib for the first-line treatment of adult patients with newly-diagnosed, Philadelphia chromosome–positive chronic myeloid leukemia (CML) in the chronic phase. The findings, along with data from the DASISION trial, which led to comparable approval of dasatinib (Sprycel), show that second-generation tyrosine kinase inhibitors (TKIs) induce faster and deeper molecular responses than does imatinib.

With three TKIs already licensed and more potentially on the way, there is a need to compare the outcomes achievable with each available agent, observed Dr. Hochhaus of Jena (Germany) University Hospital.

"Since cytogenetics is not very popular [and] PCR [polymerase chain reaction] is standardized now, at least in Europe, PCR can be used" for the 3 months’, 6 months’, and 12 months’ assessment, he suggested

The analysis presented by Dr. Hochhaus concerned only some of the patients included in the main ENESTnd study – namely, 282 patients who were treated with nilotinib at a dose of 300 mg twice daily, and 283 who were treated with 400-mg imatinib once daily.

BCR-ABL was measured after 3 and 6 months of treatment. The investigators defined progression-free survival in terms of progression to the advanced phase of disease or blast crisis, or death due to any cause; overall survival was defined as death due to any cause.

At 3 months, significantly more nilotinib-treated patients than imatinib-treated patients achieved a BCR-ABL transcript level of 10% or less (91% vs. 67%) and 1% or less (56% vs. 16%). In contrast, 33% of the imatinib-treated patients and 9% of those given nilotinib had transcript levels higher than 10%.

These 3-month transcript levels correlated with survival outcomes at 3 years’ follow-up, Dr. Hochhaus reported. In the nilotinib-treated group, 96.9% of those who achieved 1% or less and 98.8% of those who achieved up to 10% – but only 86.7% of those whose levels exceeded 10% – were alive at that point. Corresponding values for imatinib-treated patients were 95.3%, 100%, and 84.8%.

Progression-free survival rates at 3 years showed the same pattern: 96.5%, 95.6%, and 82.9%, respectively, for nilotinib-treated patients with BCR-ABL transcript levels of 1% or less, 10% or less, and more than 10% at 3 months. In the imatinib arm at 3 years’ follow-up, progression-free survival rates were 98.5%, 95.3%, and 83.8%, respectively, based on 3-month transcript levels.

Only the differences between a BCR level of 10% or less vs. more than 10% were significant for both drugs.

Similarly, progression-free survival rates at 3 years’ follow-up correlated with BCR-ABL transcript levels at 6 months. In nilotinib-treated patients, these rates were 96.5% for levels of 1% or less, 91.3% for 10% or less, and 75% for more than 10%. Corresponding values in imatinib-treated patients were 97.6%, 96.5%, and 79.7%, respectively.

Overall survival at 6 months for nilotinib and imatinib reflected the results seen at 3 months.

"Long-term outcomes for patients with more than 10% BCR-ABL levels at 3 or 6 months are worse compared to patients with less than 10% BCR-ABL when considering both progression-free survival and overall survival," Dr. Hochhaus said.

He concluded: "Nilotinib frontline allows more patients to achieve deeper responses earlier, [which is] associated with improved long-term outcomes versus imatinib."

The 3-year follow-up data from the 846-patient ENESTnd study have just been published online and were reported separately at the EHA meeting by Dr. Richard Clark, professor of hematology and consultant hematologist at the Royal Liverpool (England) University Hospital (Leukemia 2012 May 18 [doi:10.1038/leu.2012.134]).

Dr. Clark reported that – similar to previous finding – nilotinib was associated with faster and deeper molecular response rates, a lower progression to the advanced phase or blast crisis, and fewer CML-related deaths than is treatment with imatinib.

"The 3-year update shows a continuation of messages that we saw earlier in the study," Dr. Clark said. There were "significantly higher rates of all molecular responses, there’s no evidence that there is any difference according to Sokal risk in terms of outcome, and there are fewer progressions [to advanced-phase disease] on nilotinib."

The ENESTnd trial was funded by Novartis. The DASISION trial was funded by Bristol-Myers Squibb. Dr. Hochhaus and Dr. Clark had ties with Novartis, BMS, and other companies.

AMSTERDAM – Measuring BCR-ABL transcript levels at 3 and 6 months can predict the outcome of treatment with nilotinib in patients newly diagnosed with chronic myeloid leukemia, according to new data from the ENESTnd study.

Patients with lower levels at these milestones had higher rates of progression-free and overall survival, whether they received nilotinib (Tasigna) or imatinib (Gleevec) in the pivotal phase III study, investigators reported at the annual congress of the European Hematology Association (EHA).

"The main message is that for patients who are on imatinib, you have an early predictor of response that you may use the second-generation drugs if there is a problem – and the same now applies for second-generation drugs," the lead author Dr. Andreas Hochhaus, said in an interview.

The phase III ENESTnd [Evaluating Nilotinib Efficacy and Safety in Clinical Trials Newly Diagnosed Ph+ CML Patients] trial led to the approval of nilotinib for the first-line treatment of adult patients with newly-diagnosed, Philadelphia chromosome–positive chronic myeloid leukemia (CML) in the chronic phase. The findings, along with data from the DASISION trial, which led to comparable approval of dasatinib (Sprycel), show that second-generation tyrosine kinase inhibitors (TKIs) induce faster and deeper molecular responses than does imatinib.

With three TKIs already licensed and more potentially on the way, there is a need to compare the outcomes achievable with each available agent, observed Dr. Hochhaus of Jena (Germany) University Hospital.

"Since cytogenetics is not very popular [and] PCR [polymerase chain reaction] is standardized now, at least in Europe, PCR can be used" for the 3 months’, 6 months’, and 12 months’ assessment, he suggested

The analysis presented by Dr. Hochhaus concerned only some of the patients included in the main ENESTnd study – namely, 282 patients who were treated with nilotinib at a dose of 300 mg twice daily, and 283 who were treated with 400-mg imatinib once daily.

BCR-ABL was measured after 3 and 6 months of treatment. The investigators defined progression-free survival in terms of progression to the advanced phase of disease or blast crisis, or death due to any cause; overall survival was defined as death due to any cause.

At 3 months, significantly more nilotinib-treated patients than imatinib-treated patients achieved a BCR-ABL transcript level of 10% or less (91% vs. 67%) and 1% or less (56% vs. 16%). In contrast, 33% of the imatinib-treated patients and 9% of those given nilotinib had transcript levels higher than 10%.

These 3-month transcript levels correlated with survival outcomes at 3 years’ follow-up, Dr. Hochhaus reported. In the nilotinib-treated group, 96.9% of those who achieved 1% or less and 98.8% of those who achieved up to 10% – but only 86.7% of those whose levels exceeded 10% – were alive at that point. Corresponding values for imatinib-treated patients were 95.3%, 100%, and 84.8%.

Progression-free survival rates at 3 years showed the same pattern: 96.5%, 95.6%, and 82.9%, respectively, for nilotinib-treated patients with BCR-ABL transcript levels of 1% or less, 10% or less, and more than 10% at 3 months. In the imatinib arm at 3 years’ follow-up, progression-free survival rates were 98.5%, 95.3%, and 83.8%, respectively, based on 3-month transcript levels.

Only the differences between a BCR level of 10% or less vs. more than 10% were significant for both drugs.

Similarly, progression-free survival rates at 3 years’ follow-up correlated with BCR-ABL transcript levels at 6 months. In nilotinib-treated patients, these rates were 96.5% for levels of 1% or less, 91.3% for 10% or less, and 75% for more than 10%. Corresponding values in imatinib-treated patients were 97.6%, 96.5%, and 79.7%, respectively.

Overall survival at 6 months for nilotinib and imatinib reflected the results seen at 3 months.

"Long-term outcomes for patients with more than 10% BCR-ABL levels at 3 or 6 months are worse compared to patients with less than 10% BCR-ABL when considering both progression-free survival and overall survival," Dr. Hochhaus said.

He concluded: "Nilotinib frontline allows more patients to achieve deeper responses earlier, [which is] associated with improved long-term outcomes versus imatinib."

The 3-year follow-up data from the 846-patient ENESTnd study have just been published online and were reported separately at the EHA meeting by Dr. Richard Clark, professor of hematology and consultant hematologist at the Royal Liverpool (England) University Hospital (Leukemia 2012 May 18 [doi:10.1038/leu.2012.134]).

Dr. Clark reported that – similar to previous finding – nilotinib was associated with faster and deeper molecular response rates, a lower progression to the advanced phase or blast crisis, and fewer CML-related deaths than is treatment with imatinib.

"The 3-year update shows a continuation of messages that we saw earlier in the study," Dr. Clark said. There were "significantly higher rates of all molecular responses, there’s no evidence that there is any difference according to Sokal risk in terms of outcome, and there are fewer progressions [to advanced-phase disease] on nilotinib."

The ENESTnd trial was funded by Novartis. The DASISION trial was funded by Bristol-Myers Squibb. Dr. Hochhaus and Dr. Clark had ties with Novartis, BMS, and other companies.

AMSTERDAM – Measuring BCR-ABL transcript levels at 3 and 6 months can predict the outcome of treatment with nilotinib in patients newly diagnosed with chronic myeloid leukemia, according to new data from the ENESTnd study.

Patients with lower levels at these milestones had higher rates of progression-free and overall survival, whether they received nilotinib (Tasigna) or imatinib (Gleevec) in the pivotal phase III study, investigators reported at the annual congress of the European Hematology Association (EHA).

"The main message is that for patients who are on imatinib, you have an early predictor of response that you may use the second-generation drugs if there is a problem – and the same now applies for second-generation drugs," the lead author Dr. Andreas Hochhaus, said in an interview.

The phase III ENESTnd [Evaluating Nilotinib Efficacy and Safety in Clinical Trials Newly Diagnosed Ph+ CML Patients] trial led to the approval of nilotinib for the first-line treatment of adult patients with newly-diagnosed, Philadelphia chromosome–positive chronic myeloid leukemia (CML) in the chronic phase. The findings, along with data from the DASISION trial, which led to comparable approval of dasatinib (Sprycel), show that second-generation tyrosine kinase inhibitors (TKIs) induce faster and deeper molecular responses than does imatinib.

With three TKIs already licensed and more potentially on the way, there is a need to compare the outcomes achievable with each available agent, observed Dr. Hochhaus of Jena (Germany) University Hospital.

"Since cytogenetics is not very popular [and] PCR [polymerase chain reaction] is standardized now, at least in Europe, PCR can be used" for the 3 months’, 6 months’, and 12 months’ assessment, he suggested

The analysis presented by Dr. Hochhaus concerned only some of the patients included in the main ENESTnd study – namely, 282 patients who were treated with nilotinib at a dose of 300 mg twice daily, and 283 who were treated with 400-mg imatinib once daily.

BCR-ABL was measured after 3 and 6 months of treatment. The investigators defined progression-free survival in terms of progression to the advanced phase of disease or blast crisis, or death due to any cause; overall survival was defined as death due to any cause.

At 3 months, significantly more nilotinib-treated patients than imatinib-treated patients achieved a BCR-ABL transcript level of 10% or less (91% vs. 67%) and 1% or less (56% vs. 16%). In contrast, 33% of the imatinib-treated patients and 9% of those given nilotinib had transcript levels higher than 10%.

These 3-month transcript levels correlated with survival outcomes at 3 years’ follow-up, Dr. Hochhaus reported. In the nilotinib-treated group, 96.9% of those who achieved 1% or less and 98.8% of those who achieved up to 10% – but only 86.7% of those whose levels exceeded 10% – were alive at that point. Corresponding values for imatinib-treated patients were 95.3%, 100%, and 84.8%.

Progression-free survival rates at 3 years showed the same pattern: 96.5%, 95.6%, and 82.9%, respectively, for nilotinib-treated patients with BCR-ABL transcript levels of 1% or less, 10% or less, and more than 10% at 3 months. In the imatinib arm at 3 years’ follow-up, progression-free survival rates were 98.5%, 95.3%, and 83.8%, respectively, based on 3-month transcript levels.

Only the differences between a BCR level of 10% or less vs. more than 10% were significant for both drugs.

Similarly, progression-free survival rates at 3 years’ follow-up correlated with BCR-ABL transcript levels at 6 months. In nilotinib-treated patients, these rates were 96.5% for levels of 1% or less, 91.3% for 10% or less, and 75% for more than 10%. Corresponding values in imatinib-treated patients were 97.6%, 96.5%, and 79.7%, respectively.

Overall survival at 6 months for nilotinib and imatinib reflected the results seen at 3 months.

"Long-term outcomes for patients with more than 10% BCR-ABL levels at 3 or 6 months are worse compared to patients with less than 10% BCR-ABL when considering both progression-free survival and overall survival," Dr. Hochhaus said.

He concluded: "Nilotinib frontline allows more patients to achieve deeper responses earlier, [which is] associated with improved long-term outcomes versus imatinib."

The 3-year follow-up data from the 846-patient ENESTnd study have just been published online and were reported separately at the EHA meeting by Dr. Richard Clark, professor of hematology and consultant hematologist at the Royal Liverpool (England) University Hospital (Leukemia 2012 May 18 [doi:10.1038/leu.2012.134]).

Dr. Clark reported that – similar to previous finding – nilotinib was associated with faster and deeper molecular response rates, a lower progression to the advanced phase or blast crisis, and fewer CML-related deaths than is treatment with imatinib.

"The 3-year update shows a continuation of messages that we saw earlier in the study," Dr. Clark said. There were "significantly higher rates of all molecular responses, there’s no evidence that there is any difference according to Sokal risk in terms of outcome, and there are fewer progressions [to advanced-phase disease] on nilotinib."

The ENESTnd trial was funded by Novartis. The DASISION trial was funded by Bristol-Myers Squibb. Dr. Hochhaus and Dr. Clark had ties with Novartis, BMS, and other companies.

AMSTERDAM – Clinicians can use a simple tool to assess comorbidity in patients who are being considered for treatment of chronic lymphocytic leukemia in a clinical trial or routine practice, according to a retrospective analysis of data from a randomized controlled trial.

The cumulative illness rating scale (CIRS) proved to be helpful in identifying thresholds at which comorbidity might have an impact on mortality or the tolerability of chemotherapy with or without rituximab (Rituxan) in the CLL8 trial, Dr. Valentin Goede of the German Chronic Lymphocytic Leukemia Study Group (GCLLSG) reported. Patients with a high number of comorbidities or a high score in any category of comorbidity had worse outcomes in the trial.

"Chronic lymphocytic leukemia is a disease that primarily occurs in elderly patients," Dr. Goede said in an interview at the annual congress of the European Hematology Association. A relatively high proportion of patients is thus likely to have cardiovascular, metabolic, respiratory, gastrointestinal, genitourinary, neurologic, and other health problems "that might impact on the tolerability of the treatments."

How to assess the impact is not standardized, said Dr. Goede of the University of Cologne, Germany, and this compounds an existing predicament in that elderly patients and those with comorbid diseases tend to be excluded from clinical trials. A key problem is how to assess a patient’s "fitness" for treatment objectively, rather than on the basis of a physician’s clinical experience or opinion, he said.

"What the GCLLSG has done over the past 10 years is integrate a comorbidity score into our trials, [so that we can] try to have a more objective measurement of the fitness of the patients," Dr. Goede said.

For the current study, the GCLLSG looked at data from the phase III CLL8 trial to see whether the CIRS could be used to stratify patients based on their levels of comorbidity. The CLL8 trial compared fludarabine, cyclophosphamide, and rituximab (FCR) chemotherapy with FC. A total of 817 patients were involved, and while the trial excluded "unfit" patients, "it was not clear if this was the correct cutoff," said Dr. Goede.

Although the comorbidity burden was low in the population of patients studied, CIRS results correlated with overall survival and the frequency of grade 3-4 side effects, he reported. Items graded in the CIRS include cardiovascular, respiratory, gastrointestinal, genitourinary, and other categories. Each was scored individually and a total score obtained.

Patients with four or more comorbidities or with higher CIRS scores in any category (2-4) were more likely to have worse survival than were those with fewer comorbidities or lower CIRS category scores (hazard ratio, 1.9; P less than .01). If they met both of these criteria, their hazard ratio rose to 7.2 (P less than .001), when compared with patients who had fewer comorbidities or scores of 0-1 in the categories rated.

Though the number of comorbidities did not predict grade 3 or 4 toxicity, a higher score of 2-4 in any category did (P less than .001).

The CIRS might thus be a useful tool for future clinical trials "to stratify between patients who are more susceptible and less susceptible to toxicity, and [those who are susceptible] to early mortality," Dr. Goede suggested. Refinements and further validation are of course required.

"For normal practitioners, I would say that if you do this assessment in a patient, ... based on these data, you are able to anticipate the outcome of the patient a little bit," he added. This may also help identify comorbidities that need to be addressed in order to improve patients’ overall outcomes.

Compared with the complete geriatric assessment (CGA), the CIRS might be an easier tool to use in the clinic, he added. As a geriatrician and hematologist, Dr. Goede has experience with using both in clinical practice.

"The complete geriatric assessment is quite complicated, it’s very resource intensive, and it takes a very long time to do [it], and you really need people who are skilled to do the assessment," he noted. While the CGA takes about 1 hour, the CIRS takes around 1-3 minutes.

"The main problem with the CGA, as with other simple tools, is that they do not really tell you what the cutoff is," Dr. Goede added. The CGA is also not validated specifically in the hematologic setting.

The CIRS could potentially be useful in assessing comorbidity in other hematologic malignancies or tumor types, but there are no data. The tool itself is, however, validated in hospitalized patients (J. Am. Geriatr. Soc. 2008;56:1926-31) and in the family practice setting (J. Clin. Epidemiol. 2005;58:603-8).

The CLL8 study was sponsored by the GCLLSG with funding from Roche. Dr. Goede has received honoraria from Roche, Mundi-Pharma, and Gilead.

AMSTERDAM – Clinicians can use a simple tool to assess comorbidity in patients who are being considered for treatment of chronic lymphocytic leukemia in a clinical trial or routine practice, according to a retrospective analysis of data from a randomized controlled trial.

The cumulative illness rating scale (CIRS) proved to be helpful in identifying thresholds at which comorbidity might have an impact on mortality or the tolerability of chemotherapy with or without rituximab (Rituxan) in the CLL8 trial, Dr. Valentin Goede of the German Chronic Lymphocytic Leukemia Study Group (GCLLSG) reported. Patients with a high number of comorbidities or a high score in any category of comorbidity had worse outcomes in the trial.

"Chronic lymphocytic leukemia is a disease that primarily occurs in elderly patients," Dr. Goede said in an interview at the annual congress of the European Hematology Association. A relatively high proportion of patients is thus likely to have cardiovascular, metabolic, respiratory, gastrointestinal, genitourinary, neurologic, and other health problems "that might impact on the tolerability of the treatments."

How to assess the impact is not standardized, said Dr. Goede of the University of Cologne, Germany, and this compounds an existing predicament in that elderly patients and those with comorbid diseases tend to be excluded from clinical trials. A key problem is how to assess a patient’s "fitness" for treatment objectively, rather than on the basis of a physician’s clinical experience or opinion, he said.

"What the GCLLSG has done over the past 10 years is integrate a comorbidity score into our trials, [so that we can] try to have a more objective measurement of the fitness of the patients," Dr. Goede said.

For the current study, the GCLLSG looked at data from the phase III CLL8 trial to see whether the CIRS could be used to stratify patients based on their levels of comorbidity. The CLL8 trial compared fludarabine, cyclophosphamide, and rituximab (FCR) chemotherapy with FC. A total of 817 patients were involved, and while the trial excluded "unfit" patients, "it was not clear if this was the correct cutoff," said Dr. Goede.

Although the comorbidity burden was low in the population of patients studied, CIRS results correlated with overall survival and the frequency of grade 3-4 side effects, he reported. Items graded in the CIRS include cardiovascular, respiratory, gastrointestinal, genitourinary, and other categories. Each was scored individually and a total score obtained.

Patients with four or more comorbidities or with higher CIRS scores in any category (2-4) were more likely to have worse survival than were those with fewer comorbidities or lower CIRS category scores (hazard ratio, 1.9; P less than .01). If they met both of these criteria, their hazard ratio rose to 7.2 (P less than .001), when compared with patients who had fewer comorbidities or scores of 0-1 in the categories rated.

Though the number of comorbidities did not predict grade 3 or 4 toxicity, a higher score of 2-4 in any category did (P less than .001).

The CIRS might thus be a useful tool for future clinical trials "to stratify between patients who are more susceptible and less susceptible to toxicity, and [those who are susceptible] to early mortality," Dr. Goede suggested. Refinements and further validation are of course required.

"For normal practitioners, I would say that if you do this assessment in a patient, ... based on these data, you are able to anticipate the outcome of the patient a little bit," he added. This may also help identify comorbidities that need to be addressed in order to improve patients’ overall outcomes.

Compared with the complete geriatric assessment (CGA), the CIRS might be an easier tool to use in the clinic, he added. As a geriatrician and hematologist, Dr. Goede has experience with using both in clinical practice.

"The complete geriatric assessment is quite complicated, it’s very resource intensive, and it takes a very long time to do [it], and you really need people who are skilled to do the assessment," he noted. While the CGA takes about 1 hour, the CIRS takes around 1-3 minutes.

"The main problem with the CGA, as with other simple tools, is that they do not really tell you what the cutoff is," Dr. Goede added. The CGA is also not validated specifically in the hematologic setting.

The CIRS could potentially be useful in assessing comorbidity in other hematologic malignancies or tumor types, but there are no data. The tool itself is, however, validated in hospitalized patients (J. Am. Geriatr. Soc. 2008;56:1926-31) and in the family practice setting (J. Clin. Epidemiol. 2005;58:603-8).

The CLL8 study was sponsored by the GCLLSG with funding from Roche. Dr. Goede has received honoraria from Roche, Mundi-Pharma, and Gilead.

AMSTERDAM – Clinicians can use a simple tool to assess comorbidity in patients who are being considered for treatment of chronic lymphocytic leukemia in a clinical trial or routine practice, according to a retrospective analysis of data from a randomized controlled trial.

The cumulative illness rating scale (CIRS) proved to be helpful in identifying thresholds at which comorbidity might have an impact on mortality or the tolerability of chemotherapy with or without rituximab (Rituxan) in the CLL8 trial, Dr. Valentin Goede of the German Chronic Lymphocytic Leukemia Study Group (GCLLSG) reported. Patients with a high number of comorbidities or a high score in any category of comorbidity had worse outcomes in the trial.

"Chronic lymphocytic leukemia is a disease that primarily occurs in elderly patients," Dr. Goede said in an interview at the annual congress of the European Hematology Association. A relatively high proportion of patients is thus likely to have cardiovascular, metabolic, respiratory, gastrointestinal, genitourinary, neurologic, and other health problems "that might impact on the tolerability of the treatments."

How to assess the impact is not standardized, said Dr. Goede of the University of Cologne, Germany, and this compounds an existing predicament in that elderly patients and those with comorbid diseases tend to be excluded from clinical trials. A key problem is how to assess a patient’s "fitness" for treatment objectively, rather than on the basis of a physician’s clinical experience or opinion, he said.

"What the GCLLSG has done over the past 10 years is integrate a comorbidity score into our trials, [so that we can] try to have a more objective measurement of the fitness of the patients," Dr. Goede said.

For the current study, the GCLLSG looked at data from the phase III CLL8 trial to see whether the CIRS could be used to stratify patients based on their levels of comorbidity. The CLL8 trial compared fludarabine, cyclophosphamide, and rituximab (FCR) chemotherapy with FC. A total of 817 patients were involved, and while the trial excluded "unfit" patients, "it was not clear if this was the correct cutoff," said Dr. Goede.

Although the comorbidity burden was low in the population of patients studied, CIRS results correlated with overall survival and the frequency of grade 3-4 side effects, he reported. Items graded in the CIRS include cardiovascular, respiratory, gastrointestinal, genitourinary, and other categories. Each was scored individually and a total score obtained.

Patients with four or more comorbidities or with higher CIRS scores in any category (2-4) were more likely to have worse survival than were those with fewer comorbidities or lower CIRS category scores (hazard ratio, 1.9; P less than .01). If they met both of these criteria, their hazard ratio rose to 7.2 (P less than .001), when compared with patients who had fewer comorbidities or scores of 0-1 in the categories rated.

Though the number of comorbidities did not predict grade 3 or 4 toxicity, a higher score of 2-4 in any category did (P less than .001).

The CIRS might thus be a useful tool for future clinical trials "to stratify between patients who are more susceptible and less susceptible to toxicity, and [those who are susceptible] to early mortality," Dr. Goede suggested. Refinements and further validation are of course required.

"For normal practitioners, I would say that if you do this assessment in a patient, ... based on these data, you are able to anticipate the outcome of the patient a little bit," he added. This may also help identify comorbidities that need to be addressed in order to improve patients’ overall outcomes.

Compared with the complete geriatric assessment (CGA), the CIRS might be an easier tool to use in the clinic, he added. As a geriatrician and hematologist, Dr. Goede has experience with using both in clinical practice.

"The complete geriatric assessment is quite complicated, it’s very resource intensive, and it takes a very long time to do [it], and you really need people who are skilled to do the assessment," he noted. While the CGA takes about 1 hour, the CIRS takes around 1-3 minutes.

"The main problem with the CGA, as with other simple tools, is that they do not really tell you what the cutoff is," Dr. Goede added. The CGA is also not validated specifically in the hematologic setting.

The CIRS could potentially be useful in assessing comorbidity in other hematologic malignancies or tumor types, but there are no data. The tool itself is, however, validated in hospitalized patients (J. Am. Geriatr. Soc. 2008;56:1926-31) and in the family practice setting (J. Clin. Epidemiol. 2005;58:603-8).

The CLL8 study was sponsored by the GCLLSG with funding from Roche. Dr. Goede has received honoraria from Roche, Mundi-Pharma, and Gilead.

AMSTERDAM – Up to 43% of elderly patients with diffuse large B cell lymphoma might be spared radiotherapy for bulky disease, if research suggesting that there is no additional benefit when using a standard chemotherapy regimen is confirmed.

In a prospective study from Germany, patients who achieved a complete remission (CR) or complete remission unconfirmed (CRu) with R-CHOP-14 plus two subsequent doses of rituximab (Rituxan) gained no additional benefit in event-free survival (EFS), progression-free survival (PFS), or overall survival (OS), compared with a historical prospective cohort.

Sara Freeman/IMNG Medical Media

However, patients who did not achieve a CR/CRu following the chemotherapy did appear to benefit from radiotherapy to bulky disease, with higher rates on all three measures in the RICOVER-60-No-Rx trial, a German High Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL) trial,

"The role of radiotherapy in the treatment of aggressive non-Hodgkin’s lymphoma is rather unclear, especially in the rituximab era, where systemic chemotherapy has become highly effective," Dr. Gerhard Held said at the annual congress of the European Hematology Association.

"The question arises if a local therapeutic modality like radiotherapy provides benefit to patients or [if it is] just adding additional toxicity," Dr. Held of Saarland University Hospital, Homburg, Germany, added.

The RICOVER-60-No-Rx trial resulted from a protocol amendment of the previously reported RICOVER-60 trial conducted in elderly patients with diffuse large B-cell lymphoma (DLBCL). The latter involved more than 1,200 men and women with DLBCL who were aged 61-80 years.

RICOVER-60 had a 2x2 factorial design and compared six or eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone given for 14 days (CHOP-14) with or without additional rituximab (R-CHOP-14). Patients with extranodal or bulky disease, defined as a tumor of more than 7.5 cm in diameter, received additional involved-field radiotherapy of 36 Gy.

The trial’s results (Lancet Oncol. 2008;9:105-16) showed a clear benefit of adding rituximab to the CHOP-14 regimen. The aim of the RICOVER-60-No-Rx study was to look more specifically at the role of radiotherapy in patients who had received the chemotherapy regimen.

In total 166 patients received additional chemotherapy without radiotherapy after the protocol amendment, and outcome data on these patients were compared with data on 306 patients who had received R-CHOP-14 plus two additional doses of rituximab and radiotherapy to bulky disease in the RICOVER-60 trial.

Dr. Held reported that, compared with the RICOVER-60 population, those in the RICOVER-60-No-Rx trial were older (median age of 69 vs. 71 years, P = .018), more likely to have advanced (stage III/IV) disease (50% vs. 60%, P = .037), and have extranodal involvement (50% vs. 63%, P = .024). In contrast, patients in the RICOVER-60 study were more likely to have bulky disease (35 vs. 29%, P = .024).

After a median observation time of 39 months, EFS (80% vs. 54%; P = .001), PFS (88% vs. 62%; P less than .001), and OS (90% vs. 65%; P = .001) were initially higher when comparing the RICOVER-60 cohort with the RICOVER-No-Rx cohort. However, taking protocol violations and the differences in demographics into consideration, there was no difference in the three measures between the groups overall (3-year EFS and PFS: 84% vs. 75%; P = .430); OS (87% vs. 79%; P = .839). Only patients who had not adequately responded to R-CHOP 14 appeared to benefit.

This was a not a randomized investigation, Dr. Held noted, and so of course further clarification of the role of radiotherapy in DCLBL is needed. To that end, the DSHNHL UNFOLDER trial is underway; this trial is looking look at the use of radiotherapy to bulky lesions vs. observation after six cycles of treatment with R-CHOP-14 or R-CHOP 21.

Computed tomography rather than positron emission tomography was used to stage patients, Dr. Aaron Polliack, emeritus professor of hematology and former head of the lymphoma and leukemia unit at Hadassah University Hospital in Jerusalem, noted during discussion that followed.

The results of the current trial therefore warrant caution in their interpretation, suggested Dr. Polliack, who is editor in chief of the journal Leukemia and Lymphoma and not involved in the study. He further commented that no decision can truly be made on the value of radiotherapy in this clinical situation until further data from the UNFOLDER and other studies are available.

The RICOVER-60-No-Rx trial was supported by Deutsche Krebshilfe and the original RICOVER-60 trial by Roche. Dr. Held disclosed receiving travel grants from Roche. Dr. Polliack had no conflicts of interest.

AMSTERDAM – Up to 43% of elderly patients with diffuse large B cell lymphoma might be spared radiotherapy for bulky disease, if research suggesting that there is no additional benefit when using a standard chemotherapy regimen is confirmed.

In a prospective study from Germany, patients who achieved a complete remission (CR) or complete remission unconfirmed (CRu) with R-CHOP-14 plus two subsequent doses of rituximab (Rituxan) gained no additional benefit in event-free survival (EFS), progression-free survival (PFS), or overall survival (OS), compared with a historical prospective cohort.

Sara Freeman/IMNG Medical Media

However, patients who did not achieve a CR/CRu following the chemotherapy did appear to benefit from radiotherapy to bulky disease, with higher rates on all three measures in the RICOVER-60-No-Rx trial, a German High Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL) trial,

"The role of radiotherapy in the treatment of aggressive non-Hodgkin’s lymphoma is rather unclear, especially in the rituximab era, where systemic chemotherapy has become highly effective," Dr. Gerhard Held said at the annual congress of the European Hematology Association.

"The question arises if a local therapeutic modality like radiotherapy provides benefit to patients or [if it is] just adding additional toxicity," Dr. Held of Saarland University Hospital, Homburg, Germany, added.

The RICOVER-60-No-Rx trial resulted from a protocol amendment of the previously reported RICOVER-60 trial conducted in elderly patients with diffuse large B-cell lymphoma (DLBCL). The latter involved more than 1,200 men and women with DLBCL who were aged 61-80 years.

RICOVER-60 had a 2x2 factorial design and compared six or eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone given for 14 days (CHOP-14) with or without additional rituximab (R-CHOP-14). Patients with extranodal or bulky disease, defined as a tumor of more than 7.5 cm in diameter, received additional involved-field radiotherapy of 36 Gy.

The trial’s results (Lancet Oncol. 2008;9:105-16) showed a clear benefit of adding rituximab to the CHOP-14 regimen. The aim of the RICOVER-60-No-Rx study was to look more specifically at the role of radiotherapy in patients who had received the chemotherapy regimen.

In total 166 patients received additional chemotherapy without radiotherapy after the protocol amendment, and outcome data on these patients were compared with data on 306 patients who had received R-CHOP-14 plus two additional doses of rituximab and radiotherapy to bulky disease in the RICOVER-60 trial.

Dr. Held reported that, compared with the RICOVER-60 population, those in the RICOVER-60-No-Rx trial were older (median age of 69 vs. 71 years, P = .018), more likely to have advanced (stage III/IV) disease (50% vs. 60%, P = .037), and have extranodal involvement (50% vs. 63%, P = .024). In contrast, patients in the RICOVER-60 study were more likely to have bulky disease (35 vs. 29%, P = .024).

After a median observation time of 39 months, EFS (80% vs. 54%; P = .001), PFS (88% vs. 62%; P less than .001), and OS (90% vs. 65%; P = .001) were initially higher when comparing the RICOVER-60 cohort with the RICOVER-No-Rx cohort. However, taking protocol violations and the differences in demographics into consideration, there was no difference in the three measures between the groups overall (3-year EFS and PFS: 84% vs. 75%; P = .430); OS (87% vs. 79%; P = .839). Only patients who had not adequately responded to R-CHOP 14 appeared to benefit.

This was a not a randomized investigation, Dr. Held noted, and so of course further clarification of the role of radiotherapy in DCLBL is needed. To that end, the DSHNHL UNFOLDER trial is underway; this trial is looking look at the use of radiotherapy to bulky lesions vs. observation after six cycles of treatment with R-CHOP-14 or R-CHOP 21.

Computed tomography rather than positron emission tomography was used to stage patients, Dr. Aaron Polliack, emeritus professor of hematology and former head of the lymphoma and leukemia unit at Hadassah University Hospital in Jerusalem, noted during discussion that followed.

The results of the current trial therefore warrant caution in their interpretation, suggested Dr. Polliack, who is editor in chief of the journal Leukemia and Lymphoma and not involved in the study. He further commented that no decision can truly be made on the value of radiotherapy in this clinical situation until further data from the UNFOLDER and other studies are available.

The RICOVER-60-No-Rx trial was supported by Deutsche Krebshilfe and the original RICOVER-60 trial by Roche. Dr. Held disclosed receiving travel grants from Roche. Dr. Polliack had no conflicts of interest.

AMSTERDAM – Up to 43% of elderly patients with diffuse large B cell lymphoma might be spared radiotherapy for bulky disease, if research suggesting that there is no additional benefit when using a standard chemotherapy regimen is confirmed.

In a prospective study from Germany, patients who achieved a complete remission (CR) or complete remission unconfirmed (CRu) with R-CHOP-14 plus two subsequent doses of rituximab (Rituxan) gained no additional benefit in event-free survival (EFS), progression-free survival (PFS), or overall survival (OS), compared with a historical prospective cohort.

Sara Freeman/IMNG Medical Media

However, patients who did not achieve a CR/CRu following the chemotherapy did appear to benefit from radiotherapy to bulky disease, with higher rates on all three measures in the RICOVER-60-No-Rx trial, a German High Grade Non-Hodgkin’s Lymphoma Study Group (DSHNHL) trial,

"The role of radiotherapy in the treatment of aggressive non-Hodgkin’s lymphoma is rather unclear, especially in the rituximab era, where systemic chemotherapy has become highly effective," Dr. Gerhard Held said at the annual congress of the European Hematology Association.

"The question arises if a local therapeutic modality like radiotherapy provides benefit to patients or [if it is] just adding additional toxicity," Dr. Held of Saarland University Hospital, Homburg, Germany, added.

The RICOVER-60-No-Rx trial resulted from a protocol amendment of the previously reported RICOVER-60 trial conducted in elderly patients with diffuse large B-cell lymphoma (DLBCL). The latter involved more than 1,200 men and women with DLBCL who were aged 61-80 years.

RICOVER-60 had a 2x2 factorial design and compared six or eight cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone given for 14 days (CHOP-14) with or without additional rituximab (R-CHOP-14). Patients with extranodal or bulky disease, defined as a tumor of more than 7.5 cm in diameter, received additional involved-field radiotherapy of 36 Gy.

The trial’s results (Lancet Oncol. 2008;9:105-16) showed a clear benefit of adding rituximab to the CHOP-14 regimen. The aim of the RICOVER-60-No-Rx study was to look more specifically at the role of radiotherapy in patients who had received the chemotherapy regimen.

In total 166 patients received additional chemotherapy without radiotherapy after the protocol amendment, and outcome data on these patients were compared with data on 306 patients who had received R-CHOP-14 plus two additional doses of rituximab and radiotherapy to bulky disease in the RICOVER-60 trial.

Dr. Held reported that, compared with the RICOVER-60 population, those in the RICOVER-60-No-Rx trial were older (median age of 69 vs. 71 years, P = .018), more likely to have advanced (stage III/IV) disease (50% vs. 60%, P = .037), and have extranodal involvement (50% vs. 63%, P = .024). In contrast, patients in the RICOVER-60 study were more likely to have bulky disease (35 vs. 29%, P = .024).

After a median observation time of 39 months, EFS (80% vs. 54%; P = .001), PFS (88% vs. 62%; P less than .001), and OS (90% vs. 65%; P = .001) were initially higher when comparing the RICOVER-60 cohort with the RICOVER-No-Rx cohort. However, taking protocol violations and the differences in demographics into consideration, there was no difference in the three measures between the groups overall (3-year EFS and PFS: 84% vs. 75%; P = .430); OS (87% vs. 79%; P = .839). Only patients who had not adequately responded to R-CHOP 14 appeared to benefit.

This was a not a randomized investigation, Dr. Held noted, and so of course further clarification of the role of radiotherapy in DCLBL is needed. To that end, the DSHNHL UNFOLDER trial is underway; this trial is looking look at the use of radiotherapy to bulky lesions vs. observation after six cycles of treatment with R-CHOP-14 or R-CHOP 21.

Computed tomography rather than positron emission tomography was used to stage patients, Dr. Aaron Polliack, emeritus professor of hematology and former head of the lymphoma and leukemia unit at Hadassah University Hospital in Jerusalem, noted during discussion that followed.

The results of the current trial therefore warrant caution in their interpretation, suggested Dr. Polliack, who is editor in chief of the journal Leukemia and Lymphoma and not involved in the study. He further commented that no decision can truly be made on the value of radiotherapy in this clinical situation until further data from the UNFOLDER and other studies are available.

The RICOVER-60-No-Rx trial was supported by Deutsche Krebshilfe and the original RICOVER-60 trial by Roche. Dr. Held disclosed receiving travel grants from Roche. Dr. Polliack had no conflicts of interest.

AMSTERDAM – Stopping imatinib in patients who have achieved stable remission of chronic myeloid leukemia for at least 2 years appears to be a safe therapeutic strategy, according to updated results of the Australasian Leukemia and Lymphoma CML-8 trial.

"Approximately 40% of patients who had been in a stable complete molecular response and stopped their treatment are in a complete molecular response with a median follow-up of 3 years," said consultant hematologist Dr. David Ross in an interview at the annual congress of the European Hematology Association.

As of April 2012, 18 of 40 patients remained in stable complete molecular remission (CMR) while off treatment. Although 22 patients had a molecular recurrence at some point after imatinib (Gleevec) withdrawal, they all responded to the reintroduction of imatinib, with most patients rapidly regaining CMR.

These data build on those already released from the STIM (Stop Imatinib) trial (Lancet Oncol. 2010;11:1029-35) and the STOP 2G-TKI study, which have also shown that imatinib, dasatinib (Sprycel), and nilotinib (Tasigna) withdrawal is a feasible therapeutic strategy for some patients with chronic myeloid leukemia (CML).

The CML-8 trial involved 40 adult patients who had been treated with imatinib for at least 3 years and were in CMR for at least 2 years. CMR was defined as no detectable BCR-ABL mRNA as determined by real-time quantitative polymerase chain reaction (RT-PCR) analysis. The latter was checked every month during the first year after imatinib withdrawal, every 2 months in the second year, and then every 3 months for up to 5 years of total follow-up. The last patient entered the trial in 2011, so further data from the trial are likely in the future.

"We’ve not seen any relapses later than 2 years," said Dr. Ross, of SA Pathology and Flinders Medical Centre in Adelaide, Australia.

"If I were designing the study again now, I would only do the monthly testing for 6 months because all of the action is in the first 6 months," Dr. Ross said.

The median age of patients participating in the study was 60 years. The median duration of imatinib therapy prior to withdrawal was 5.8 years (range, 3-9 years).

Although it is much smaller, the CML-8 trial provides findings similar to those of the French STIM study, Dr. Ross said. "We have seen an almost identical rate of sustained molecular response," he observed.

"We’ve also seen that the strongest predictor [for relapse] is the Sokal score, which suggests that unfavorable disease biology at the very beginning is still, after all these years of treatment, the single most important predictor of relapse risk."

Univariate analysis showed a higher percentage of patients with a low to intermediate Sokal score remaining relapse free compared with those with a high Sokal score (49.3% vs. 14.3% of 35 patients, P = .002).

One year of prior interferon therapy was also found to be predictive of relapse-free survival, with patients who had taken interferon for 1 year faring significantly better than those who had taken it for less than 1 year (60% vs. 20% of 21 patients, P = .0042).

"Again, if you stayed on interferon for more than 12 months it means that you had a good response to interferon, so it’s probably telling you the same thing in a different way," Dr. Ross suggested.

"I think the next step from this [CML-8 study] is to look at what is going to happen with the second-generation drugs," he added. "With the increasing use of nilotinib and dasatinib, the number of patients on imatinib is potentially going to diminish."

Another possible research question, Dr. Ross said, was to determine whether there is any value in pushing patients to achieve a CMR (that is, no detectable BCR-ABL) over achieving a major molecular response (MMR), in which BCR-ABL falls to less than 0.1%.

One trial that will look further at the issue of stopping tyrosine kinase inhibitors (TKIs) in CML is the EURO-SKI (European Stop Kinase Inhibitor) study. This multicenter, open-label, uncontrolled trial is being run by the European LeukemiaNet, and has just started to accrue patients.

"We hope to accrue 500 patients," said the trial’s principal investigator Dr. Susanne Saussele in an interview. Dr. Saussele of the University Medical Centre Mannheim and the University of Heidelberg, both in Germany, noted, however, that the trial does not have the backing of pharmaceutical companies, so getting funding is proving to be a challenge for some countries. To date, the trial has only started in Germany and in Sweden.

The primary aim is to estimate the persistence of molecular remission in CML after stopping treatment with available TKIs. EURO-SKI will measure MMR 4 (BCR-ABL of 0.01% or less) and MMR (BCR-ABL of 0.1% or less). Patients will need to achieve MMR 4 for at least 1 year before they can stop TKI therapy, and will have reached the end point if they lose MMR and the BCR-ABL transcript level rises over the 0.1% threshold.

"We are using MMR, which is one log higher than MMR 4 used in the STIM study," Dr. Saussele said. "This is because the STIM study showed that a lot of patients are between MMR4 and MMR."

The estimated date for completion of the trial is June 2017, with the first data available from the trial expected in roughly 3 years’ time.

The CML-8 study was conducted by the Australasian Leukemia and Lymphoma Group with funding from Novartis. Dr. Ross has received research funding and honoraria from Novartis. Dr. Saussele had no disclosures.

AMSTERDAM – Stopping imatinib in patients who have achieved stable remission of chronic myeloid leukemia for at least 2 years appears to be a safe therapeutic strategy, according to updated results of the Australasian Leukemia and Lymphoma CML-8 trial.

"Approximately 40% of patients who had been in a stable complete molecular response and stopped their treatment are in a complete molecular response with a median follow-up of 3 years," said consultant hematologist Dr. David Ross in an interview at the annual congress of the European Hematology Association.

As of April 2012, 18 of 40 patients remained in stable complete molecular remission (CMR) while off treatment. Although 22 patients had a molecular recurrence at some point after imatinib (Gleevec) withdrawal, they all responded to the reintroduction of imatinib, with most patients rapidly regaining CMR.

These data build on those already released from the STIM (Stop Imatinib) trial (Lancet Oncol. 2010;11:1029-35) and the STOP 2G-TKI study, which have also shown that imatinib, dasatinib (Sprycel), and nilotinib (Tasigna) withdrawal is a feasible therapeutic strategy for some patients with chronic myeloid leukemia (CML).

The CML-8 trial involved 40 adult patients who had been treated with imatinib for at least 3 years and were in CMR for at least 2 years. CMR was defined as no detectable BCR-ABL mRNA as determined by real-time quantitative polymerase chain reaction (RT-PCR) analysis. The latter was checked every month during the first year after imatinib withdrawal, every 2 months in the second year, and then every 3 months for up to 5 years of total follow-up. The last patient entered the trial in 2011, so further data from the trial are likely in the future.

"We’ve not seen any relapses later than 2 years," said Dr. Ross, of SA Pathology and Flinders Medical Centre in Adelaide, Australia.

"If I were designing the study again now, I would only do the monthly testing for 6 months because all of the action is in the first 6 months," Dr. Ross said.

The median age of patients participating in the study was 60 years. The median duration of imatinib therapy prior to withdrawal was 5.8 years (range, 3-9 years).

Although it is much smaller, the CML-8 trial provides findings similar to those of the French STIM study, Dr. Ross said. "We have seen an almost identical rate of sustained molecular response," he observed.

"We’ve also seen that the strongest predictor [for relapse] is the Sokal score, which suggests that unfavorable disease biology at the very beginning is still, after all these years of treatment, the single most important predictor of relapse risk."

Univariate analysis showed a higher percentage of patients with a low to intermediate Sokal score remaining relapse free compared with those with a high Sokal score (49.3% vs. 14.3% of 35 patients, P = .002).

One year of prior interferon therapy was also found to be predictive of relapse-free survival, with patients who had taken interferon for 1 year faring significantly better than those who had taken it for less than 1 year (60% vs. 20% of 21 patients, P = .0042).

"Again, if you stayed on interferon for more than 12 months it means that you had a good response to interferon, so it’s probably telling you the same thing in a different way," Dr. Ross suggested.

"I think the next step from this [CML-8 study] is to look at what is going to happen with the second-generation drugs," he added. "With the increasing use of nilotinib and dasatinib, the number of patients on imatinib is potentially going to diminish."

Another possible research question, Dr. Ross said, was to determine whether there is any value in pushing patients to achieve a CMR (that is, no detectable BCR-ABL) over achieving a major molecular response (MMR), in which BCR-ABL falls to less than 0.1%.

One trial that will look further at the issue of stopping tyrosine kinase inhibitors (TKIs) in CML is the EURO-SKI (European Stop Kinase Inhibitor) study. This multicenter, open-label, uncontrolled trial is being run by the European LeukemiaNet, and has just started to accrue patients.

"We hope to accrue 500 patients," said the trial’s principal investigator Dr. Susanne Saussele in an interview. Dr. Saussele of the University Medical Centre Mannheim and the University of Heidelberg, both in Germany, noted, however, that the trial does not have the backing of pharmaceutical companies, so getting funding is proving to be a challenge for some countries. To date, the trial has only started in Germany and in Sweden.

The primary aim is to estimate the persistence of molecular remission in CML after stopping treatment with available TKIs. EURO-SKI will measure MMR 4 (BCR-ABL of 0.01% or less) and MMR (BCR-ABL of 0.1% or less). Patients will need to achieve MMR 4 for at least 1 year before they can stop TKI therapy, and will have reached the end point if they lose MMR and the BCR-ABL transcript level rises over the 0.1% threshold.

"We are using MMR, which is one log higher than MMR 4 used in the STIM study," Dr. Saussele said. "This is because the STIM study showed that a lot of patients are between MMR4 and MMR."

The estimated date for completion of the trial is June 2017, with the first data available from the trial expected in roughly 3 years’ time.

The CML-8 study was conducted by the Australasian Leukemia and Lymphoma Group with funding from Novartis. Dr. Ross has received research funding and honoraria from Novartis. Dr. Saussele had no disclosures.

AMSTERDAM – Stopping imatinib in patients who have achieved stable remission of chronic myeloid leukemia for at least 2 years appears to be a safe therapeutic strategy, according to updated results of the Australasian Leukemia and Lymphoma CML-8 trial.

"Approximately 40% of patients who had been in a stable complete molecular response and stopped their treatment are in a complete molecular response with a median follow-up of 3 years," said consultant hematologist Dr. David Ross in an interview at the annual congress of the European Hematology Association.

As of April 2012, 18 of 40 patients remained in stable complete molecular remission (CMR) while off treatment. Although 22 patients had a molecular recurrence at some point after imatinib (Gleevec) withdrawal, they all responded to the reintroduction of imatinib, with most patients rapidly regaining CMR.

These data build on those already released from the STIM (Stop Imatinib) trial (Lancet Oncol. 2010;11:1029-35) and the STOP 2G-TKI study, which have also shown that imatinib, dasatinib (Sprycel), and nilotinib (Tasigna) withdrawal is a feasible therapeutic strategy for some patients with chronic myeloid leukemia (CML).

The CML-8 trial involved 40 adult patients who had been treated with imatinib for at least 3 years and were in CMR for at least 2 years. CMR was defined as no detectable BCR-ABL mRNA as determined by real-time quantitative polymerase chain reaction (RT-PCR) analysis. The latter was checked every month during the first year after imatinib withdrawal, every 2 months in the second year, and then every 3 months for up to 5 years of total follow-up. The last patient entered the trial in 2011, so further data from the trial are likely in the future.

"We’ve not seen any relapses later than 2 years," said Dr. Ross, of SA Pathology and Flinders Medical Centre in Adelaide, Australia.

"If I were designing the study again now, I would only do the monthly testing for 6 months because all of the action is in the first 6 months," Dr. Ross said.

The median age of patients participating in the study was 60 years. The median duration of imatinib therapy prior to withdrawal was 5.8 years (range, 3-9 years).

Although it is much smaller, the CML-8 trial provides findings similar to those of the French STIM study, Dr. Ross said. "We have seen an almost identical rate of sustained molecular response," he observed.

"We’ve also seen that the strongest predictor [for relapse] is the Sokal score, which suggests that unfavorable disease biology at the very beginning is still, after all these years of treatment, the single most important predictor of relapse risk."

Univariate analysis showed a higher percentage of patients with a low to intermediate Sokal score remaining relapse free compared with those with a high Sokal score (49.3% vs. 14.3% of 35 patients, P = .002).

One year of prior interferon therapy was also found to be predictive of relapse-free survival, with patients who had taken interferon for 1 year faring significantly better than those who had taken it for less than 1 year (60% vs. 20% of 21 patients, P = .0042).

"Again, if you stayed on interferon for more than 12 months it means that you had a good response to interferon, so it’s probably telling you the same thing in a different way," Dr. Ross suggested.

"I think the next step from this [CML-8 study] is to look at what is going to happen with the second-generation drugs," he added. "With the increasing use of nilotinib and dasatinib, the number of patients on imatinib is potentially going to diminish."

Another possible research question, Dr. Ross said, was to determine whether there is any value in pushing patients to achieve a CMR (that is, no detectable BCR-ABL) over achieving a major molecular response (MMR), in which BCR-ABL falls to less than 0.1%.

One trial that will look further at the issue of stopping tyrosine kinase inhibitors (TKIs) in CML is the EURO-SKI (European Stop Kinase Inhibitor) study. This multicenter, open-label, uncontrolled trial is being run by the European LeukemiaNet, and has just started to accrue patients.

"We hope to accrue 500 patients," said the trial’s principal investigator Dr. Susanne Saussele in an interview. Dr. Saussele of the University Medical Centre Mannheim and the University of Heidelberg, both in Germany, noted, however, that the trial does not have the backing of pharmaceutical companies, so getting funding is proving to be a challenge for some countries. To date, the trial has only started in Germany and in Sweden.

The primary aim is to estimate the persistence of molecular remission in CML after stopping treatment with available TKIs. EURO-SKI will measure MMR 4 (BCR-ABL of 0.01% or less) and MMR (BCR-ABL of 0.1% or less). Patients will need to achieve MMR 4 for at least 1 year before they can stop TKI therapy, and will have reached the end point if they lose MMR and the BCR-ABL transcript level rises over the 0.1% threshold.

"We are using MMR, which is one log higher than MMR 4 used in the STIM study," Dr. Saussele said. "This is because the STIM study showed that a lot of patients are between MMR4 and MMR."

The estimated date for completion of the trial is June 2017, with the first data available from the trial expected in roughly 3 years’ time.

The CML-8 study was conducted by the Australasian Leukemia and Lymphoma Group with funding from Novartis. Dr. Ross has received research funding and honoraria from Novartis. Dr. Saussele had no disclosures.

AMSTERDAM – Standard drugs commonly used to treat patients with hematologic and other malignancies are in worryingly short supply, not only in the United States, but also around the globe – a situation that has prompted three leading U.S. and European societies to issue an urgent call to action.

The American Society for Hematology (ASH), the European Hematology Association (EHA), and the European Cancer Patient Coalition (ECPC) issued joint statements June 16 to highlight the problem, which affects the care of patients with leukemia, lymphoma, myeloma, and other life-threatening blood disorders.

The international collaborative announced it would collect data on drug shortages and report the information to the respective authorities, as has been done in the United States. In addition, it "pledged to support legislation in the United States, Europe, and around the world that provides clear, effective interventions to alleviate drug shortages."

"Medicine should be available for any patient who needs it and there should be no barriers to access medicine."

Europe Takes Action

"In the United States, legislation is well under way that may curb drug shortages," Dr. Ulrich Jäger of the Medical University of Vienna, noted in the EHA press statement.

"In Europe, we do not even have a proper understanding of the problem," the EHA president added. "We must work together with our partners to raise awareness and protect the heath of patients with blood disorders worldwide."

In addition to issuing joint press statements, the societies used the joint ESH-ASH symposium at the annual congress of the European Hematology Association to highlight the issue. From the patient’s perspective, it is one of the most basic human rights to be given appropriate access to health care, said Viorica Cursaru, the president of Myeloma Euronet Romania, a member of the ECPC.

Ms. Cursaru noted that the EU health commissioner had stated that the ultimate objective of the EU is to have patients treated well in their own countries and that the time had come to implement Europewide strategies for health.

For this to happen, she argued, there needs to be not only a harmonized legal framework, but also appropriate infrastructure that is lacking in many, particularly eastern European, countries, the professional staff to implement changes, and the political will at both an EU and at a national level.

Big Pharma’s Perspective

Giving the European Federation of Pharmaceutical Industries and Associations (EFPIA), perspective, Brendan Barnes said that medicine shortages come down to more than just the price and availability; the issue is also about affordability and economic viability. EFPIA is a trade association representing the interests of the research-based pharmaceutical industry,

"We are private sector entities and we need to have a basis to do the business," Mr. Barnes maintained. While the industry wants to do all it can to ensure the adequate provision of drugs to everyone in need, via patient access schemes and reimbursement, accessibility, and affordability ultimately also comes down to local governments and their policies.

"We look to governments to support innovation through fair prices. We look to them for adequately resourced health systems, but health is a right we can only deliver if governments invest in health systems," Mr. Barnes said.

Changing the law is one thing, he said, but there also needs to be a health system in place to ensure that health interventions can successfully be delivered.

European Situation More Complex

"There are two issues at stake here as far as I can see, first is availability and second affordability," said hematologist Dr. Anton Hagenbeek of the Academic Medical Center at the University of Amsterdam in the Netherlands.

ASH is well ahead of the EU in keeping track of the drugs shortages problem, Dr. Hagenbeek observed. Indeed, ASH has collected data on hematologic drug shortages via its dedicated drug shortages portal for the past 18 months and regularly reports its findings to the Food & Drug Administration.

Drugs currently on the ASH/FDA shortage list include many generic, injectable drugs, including methotrexate, leucovorin, bleomycin, anthracyclines, and cisplatin, to name a few. According to the ASH press statement, more that 200 drugs were reported to be in short supply in the United States at one point last year, several dozen of which were critical to the care of patients with hematologic disorders.

The situation in Europe is undoubtedly more complex than in the United States, Dr. Hagenbeek observed. "We are not 1 country; we are 27 countries with our own rules and regulations."

Although it seems as if the EU has fewer drug shortages, compared with the United States, the number of incidents is increasing annually, he noted, citing a sudden shortage last year of cytosine arabinoside in the Netherlands.

The lack of an inventory to keep track of shortages needs addressing, Dr. Hagenbeek said. "Medicine should be available for any patient who needs it and there should be no barriers to access medicine," he said.

"Imagine AML induction without cytosine arabinoside, ALL induction without methotrexate and vincristine, and BEAM without the B, E, and A," Dr. Hagenbeek noted. This is a situation that is "simply unacceptable" for both hematologists as well as patients.

Following the U.S. Example

Speaking from the EHA’s perspective, Dr. Hagenbeek commented that European hematologists should follow the lead set by the United States by creating drug shortage databases in their respective countries and also by reporting drug shortages directly to the society.

Raising awareness is the start, Dr. Hagenbeek suggested. Notification of health authorities, and ultimately, hopefully changing European legislation will be the important next steps.

"EHA is in an excellent position to build on what we have already achieved as ASH in influencing legislation as a first step in dealing with the drug shortage issue," ASH president Armand Keating of the University of Toronto and the Princess Margaret Hospital in Toronto said in an interview.

"I think there are a number of potential solutions," Dr. Keating added, suggesting that an incentive-based rather than punitive-based system might be more successful in addressing drug shortages in the United States in particular.

"One of the things hematologists can do is inform patients about the issue," Dr. Keating suggested, as well as reporting drug shortages to their national health authorities and professional societies such as ASH and EHA.

Dr. Keating, Dr. Jäger, Ms. Cursaru, Mr. Barnes, and Dr. Hagenbeek had no relevant conflicts of interest other than representing their respective societies or professions.

AMSTERDAM – Standard drugs commonly used to treat patients with hematologic and other malignancies are in worryingly short supply, not only in the United States, but also around the globe – a situation that has prompted three leading U.S. and European societies to issue an urgent call to action.

The American Society for Hematology (ASH), the European Hematology Association (EHA), and the European Cancer Patient Coalition (ECPC) issued joint statements June 16 to highlight the problem, which affects the care of patients with leukemia, lymphoma, myeloma, and other life-threatening blood disorders.

The international collaborative announced it would collect data on drug shortages and report the information to the respective authorities, as has been done in the United States. In addition, it "pledged to support legislation in the United States, Europe, and around the world that provides clear, effective interventions to alleviate drug shortages."

"Medicine should be available for any patient who needs it and there should be no barriers to access medicine."

Europe Takes Action

"In the United States, legislation is well under way that may curb drug shortages," Dr. Ulrich Jäger of the Medical University of Vienna, noted in the EHA press statement.

"In Europe, we do not even have a proper understanding of the problem," the EHA president added. "We must work together with our partners to raise awareness and protect the heath of patients with blood disorders worldwide."

In addition to issuing joint press statements, the societies used the joint ESH-ASH symposium at the annual congress of the European Hematology Association to highlight the issue. From the patient’s perspective, it is one of the most basic human rights to be given appropriate access to health care, said Viorica Cursaru, the president of Myeloma Euronet Romania, a member of the ECPC.

Ms. Cursaru noted that the EU health commissioner had stated that the ultimate objective of the EU is to have patients treated well in their own countries and that the time had come to implement Europewide strategies for health.

For this to happen, she argued, there needs to be not only a harmonized legal framework, but also appropriate infrastructure that is lacking in many, particularly eastern European, countries, the professional staff to implement changes, and the political will at both an EU and at a national level.

Big Pharma’s Perspective

Giving the European Federation of Pharmaceutical Industries and Associations (EFPIA), perspective, Brendan Barnes said that medicine shortages come down to more than just the price and availability; the issue is also about affordability and economic viability. EFPIA is a trade association representing the interests of the research-based pharmaceutical industry,

"We are private sector entities and we need to have a basis to do the business," Mr. Barnes maintained. While the industry wants to do all it can to ensure the adequate provision of drugs to everyone in need, via patient access schemes and reimbursement, accessibility, and affordability ultimately also comes down to local governments and their policies.

"We look to governments to support innovation through fair prices. We look to them for adequately resourced health systems, but health is a right we can only deliver if governments invest in health systems," Mr. Barnes said.

Changing the law is one thing, he said, but there also needs to be a health system in place to ensure that health interventions can successfully be delivered.

European Situation More Complex

"There are two issues at stake here as far as I can see, first is availability and second affordability," said hematologist Dr. Anton Hagenbeek of the Academic Medical Center at the University of Amsterdam in the Netherlands.

ASH is well ahead of the EU in keeping track of the drugs shortages problem, Dr. Hagenbeek observed. Indeed, ASH has collected data on hematologic drug shortages via its dedicated drug shortages portal for the past 18 months and regularly reports its findings to the Food & Drug Administration.

Drugs currently on the ASH/FDA shortage list include many generic, injectable drugs, including methotrexate, leucovorin, bleomycin, anthracyclines, and cisplatin, to name a few. According to the ASH press statement, more that 200 drugs were reported to be in short supply in the United States at one point last year, several dozen of which were critical to the care of patients with hematologic disorders.

The situation in Europe is undoubtedly more complex than in the United States, Dr. Hagenbeek observed. "We are not 1 country; we are 27 countries with our own rules and regulations."

Although it seems as if the EU has fewer drug shortages, compared with the United States, the number of incidents is increasing annually, he noted, citing a sudden shortage last year of cytosine arabinoside in the Netherlands.

The lack of an inventory to keep track of shortages needs addressing, Dr. Hagenbeek said. "Medicine should be available for any patient who needs it and there should be no barriers to access medicine," he said.

"Imagine AML induction without cytosine arabinoside, ALL induction without methotrexate and vincristine, and BEAM without the B, E, and A," Dr. Hagenbeek noted. This is a situation that is "simply unacceptable" for both hematologists as well as patients.

Following the U.S. Example

Speaking from the EHA’s perspective, Dr. Hagenbeek commented that European hematologists should follow the lead set by the United States by creating drug shortage databases in their respective countries and also by reporting drug shortages directly to the society.

Raising awareness is the start, Dr. Hagenbeek suggested. Notification of health authorities, and ultimately, hopefully changing European legislation will be the important next steps.

"EHA is in an excellent position to build on what we have already achieved as ASH in influencing legislation as a first step in dealing with the drug shortage issue," ASH president Armand Keating of the University of Toronto and the Princess Margaret Hospital in Toronto said in an interview.

"I think there are a number of potential solutions," Dr. Keating added, suggesting that an incentive-based rather than punitive-based system might be more successful in addressing drug shortages in the United States in particular.

"One of the things hematologists can do is inform patients about the issue," Dr. Keating suggested, as well as reporting drug shortages to their national health authorities and professional societies such as ASH and EHA.

Dr. Keating, Dr. Jäger, Ms. Cursaru, Mr. Barnes, and Dr. Hagenbeek had no relevant conflicts of interest other than representing their respective societies or professions.

AMSTERDAM – Standard drugs commonly used to treat patients with hematologic and other malignancies are in worryingly short supply, not only in the United States, but also around the globe – a situation that has prompted three leading U.S. and European societies to issue an urgent call to action.

The American Society for Hematology (ASH), the European Hematology Association (EHA), and the European Cancer Patient Coalition (ECPC) issued joint statements June 16 to highlight the problem, which affects the care of patients with leukemia, lymphoma, myeloma, and other life-threatening blood disorders.

The international collaborative announced it would collect data on drug shortages and report the information to the respective authorities, as has been done in the United States. In addition, it "pledged to support legislation in the United States, Europe, and around the world that provides clear, effective interventions to alleviate drug shortages."

"Medicine should be available for any patient who needs it and there should be no barriers to access medicine."

Europe Takes Action

"In the United States, legislation is well under way that may curb drug shortages," Dr. Ulrich Jäger of the Medical University of Vienna, noted in the EHA press statement.

"In Europe, we do not even have a proper understanding of the problem," the EHA president added. "We must work together with our partners to raise awareness and protect the heath of patients with blood disorders worldwide."

In addition to issuing joint press statements, the societies used the joint ESH-ASH symposium at the annual congress of the European Hematology Association to highlight the issue. From the patient’s perspective, it is one of the most basic human rights to be given appropriate access to health care, said Viorica Cursaru, the president of Myeloma Euronet Romania, a member of the ECPC.

Ms. Cursaru noted that the EU health commissioner had stated that the ultimate objective of the EU is to have patients treated well in their own countries and that the time had come to implement Europewide strategies for health.

For this to happen, she argued, there needs to be not only a harmonized legal framework, but also appropriate infrastructure that is lacking in many, particularly eastern European, countries, the professional staff to implement changes, and the political will at both an EU and at a national level.

Big Pharma’s Perspective

Giving the European Federation of Pharmaceutical Industries and Associations (EFPIA), perspective, Brendan Barnes said that medicine shortages come down to more than just the price and availability; the issue is also about affordability and economic viability. EFPIA is a trade association representing the interests of the research-based pharmaceutical industry,

"We are private sector entities and we need to have a basis to do the business," Mr. Barnes maintained. While the industry wants to do all it can to ensure the adequate provision of drugs to everyone in need, via patient access schemes and reimbursement, accessibility, and affordability ultimately also comes down to local governments and their policies.

"We look to governments to support innovation through fair prices. We look to them for adequately resourced health systems, but health is a right we can only deliver if governments invest in health systems," Mr. Barnes said.

Changing the law is one thing, he said, but there also needs to be a health system in place to ensure that health interventions can successfully be delivered.

European Situation More Complex

"There are two issues at stake here as far as I can see, first is availability and second affordability," said hematologist Dr. Anton Hagenbeek of the Academic Medical Center at the University of Amsterdam in the Netherlands.

ASH is well ahead of the EU in keeping track of the drugs shortages problem, Dr. Hagenbeek observed. Indeed, ASH has collected data on hematologic drug shortages via its dedicated drug shortages portal for the past 18 months and regularly reports its findings to the Food & Drug Administration.

Drugs currently on the ASH/FDA shortage list include many generic, injectable drugs, including methotrexate, leucovorin, bleomycin, anthracyclines, and cisplatin, to name a few. According to the ASH press statement, more that 200 drugs were reported to be in short supply in the United States at one point last year, several dozen of which were critical to the care of patients with hematologic disorders.

The situation in Europe is undoubtedly more complex than in the United States, Dr. Hagenbeek observed. "We are not 1 country; we are 27 countries with our own rules and regulations."

Although it seems as if the EU has fewer drug shortages, compared with the United States, the number of incidents is increasing annually, he noted, citing a sudden shortage last year of cytosine arabinoside in the Netherlands.

The lack of an inventory to keep track of shortages needs addressing, Dr. Hagenbeek said. "Medicine should be available for any patient who needs it and there should be no barriers to access medicine," he said.

"Imagine AML induction without cytosine arabinoside, ALL induction without methotrexate and vincristine, and BEAM without the B, E, and A," Dr. Hagenbeek noted. This is a situation that is "simply unacceptable" for both hematologists as well as patients.

Following the U.S. Example

Speaking from the EHA’s perspective, Dr. Hagenbeek commented that European hematologists should follow the lead set by the United States by creating drug shortage databases in their respective countries and also by reporting drug shortages directly to the society.

Raising awareness is the start, Dr. Hagenbeek suggested. Notification of health authorities, and ultimately, hopefully changing European legislation will be the important next steps.

"EHA is in an excellent position to build on what we have already achieved as ASH in influencing legislation as a first step in dealing with the drug shortage issue," ASH president Armand Keating of the University of Toronto and the Princess Margaret Hospital in Toronto said in an interview.

"I think there are a number of potential solutions," Dr. Keating added, suggesting that an incentive-based rather than punitive-based system might be more successful in addressing drug shortages in the United States in particular.

"One of the things hematologists can do is inform patients about the issue," Dr. Keating suggested, as well as reporting drug shortages to their national health authorities and professional societies such as ASH and EHA.

Dr. Keating, Dr. Jäger, Ms. Cursaru, Mr. Barnes, and Dr. Hagenbeek had no relevant conflicts of interest other than representing their respective societies or professions.

AMSTERDAM – Crizotinib has shown significant antitumor activity in adult patients with lymphomas that express the anaplastic lymphoma kinase gene and who were resistant to the effects of at least three lines of previous therapy.

During a compassionate use program, eight of nine patients with anaplastic lymphoma kinase (ALK)–positive lymphoma responded to crizotinib (Xalkori). Six patients had complete responses, and four achieved durable responses lasting more than 6 months.

Sara Freeman/IMNG Medical Media

These data mirror positive early results already seen in pediatric anaplastic large cell lymphoma (ALCL). Seven of eight children treated with crizotinib had complete and durable responses, investigators reported at the American Society of Clinical Oncology annual meeting.

"Clinically, ALK+ lymphomas are known for their aggressiveness," said Dr. Carlo Gambacorti-Passerini, who presented the adult findings June 17 at the annual congress of the European Hematology Association. These data give a strong signal that further investigation in ALK-positive lymphomas is warranted.

Crizotinib was approved by the Food and Drug Administration for the treatment of ALK-driven non–small cell lung cancer (NSCLC) last August, but these new data suggest that responses may be even better in these lymphoma patients.

"It looks like, compared to EMF4-ALK-positive non–small cell lung cancer, the responses are much more durable," observed Dr. Matthias Theobald of Medizinische Klinik und Poliklink in Mainz, Germany, who chaired the session in which the adult findings were presented.

"Why lung cancer patients only have a median duration of responses of 10-12 months is not very clear," responded Dr. Carlo Gambacorti-Passerini, professor of internal medicine at the University of Milan–Bicocca and director of the clinical research unit at S. Gerardo Hospital, both in Monza, Italy.

It is also not apparent why some patients with ALK-positive lymphoma initially benefit while others develop resistance with time. "The main issue here is that [nearly] everybody responds, but after 2-3 months we see a divide," Dr. Gambacorti-Passerini said.

Four men and five women aged between 20 and 56 years (median age, 31 years) received crizotinib at a dose of 250 mg twice daily as part of a compassionate protocol. Seven patients had ALCL, and two patients had diffuse large cell lymphoma according to WHO criteria.

The median number of previous lines of therapy they had collectively received was three, although some had received up to five prior chemotherapy regimens, three had undergone autologous bone marrow transplant, and one patient an allogenic bone marrow transplant. While on crizotinib, steroid use or the use of drugs with antineoplastic activity was not allowed.

The effects of crizotinib were carefully assessed via physical exam, examination of bone marrow aspirate, positron-emission tomography and computed tomography scans, and blood tests before treatment initiation and at monthly intervals for the first 3 months, then every 3 months for up to 2 years. Disease status was also evaluated according to standard RECIST criteria.

After a median follow-up of 8 months, six patients had achieved a complete response to crizotinib, lasting for 2, 5, 8, 13, 18, or 24 months or more, respectively. A further two patients had a partial response.

Dr. Gambacorti-Passerini reported responses to treatment were "very rapid," with alleviation of fever within 2-10 days and time to normalization of serum lactate dehydrogenase within a month.

Furthermore, three patients were still on treatment with crizotinib. Six patients had discontinued: one because of patient request and five because of disease progression. The patient who discontinued by request did so because of severe gastroparesis unrelated to crizotinib and after a planned stoppage of the drug for a stem cell transplant.

Importantly, overall survival at 24 months appears to be just over 40%.

The most common side effects and lab abnormalities were ocular flashes, which all nine patients experienced, but these were of grade 1 or 2 and usually a temporary effect; one patient each had a grade 1-2 peripheral edema, a grade 3 neutropenia, and a grade 2 liver function test abnormality.

"These data show that crizotinib was well tolerated in this population of heavily pretreated patients," Dr. Gambacorti-Passerini concluded. He noted that patients have been treated with crizotinib for 2 years or more, which is the longest anyone has received the drug.

"Now, crizotinib is being evaluated in a registration study, which will start after this compassionate use," he added. This international phase I study (NCT01121588) is currently enrolling patients, and there are also suggestions of using crizotinib as first-line treatment or in combination with other agents for ALK+ lymphomas.

Dr. Gambacorti-Passerini has received research funding from Pfizer, which supported the compassionate use program.

AMSTERDAM – Crizotinib has shown significant antitumor activity in adult patients with lymphomas that express the anaplastic lymphoma kinase gene and who were resistant to the effects of at least three lines of previous therapy.

During a compassionate use program, eight of nine patients with anaplastic lymphoma kinase (ALK)–positive lymphoma responded to crizotinib (Xalkori). Six patients had complete responses, and four achieved durable responses lasting more than 6 months.

Sara Freeman/IMNG Medical Media

These data mirror positive early results already seen in pediatric anaplastic large cell lymphoma (ALCL). Seven of eight children treated with crizotinib had complete and durable responses, investigators reported at the American Society of Clinical Oncology annual meeting.

"Clinically, ALK+ lymphomas are known for their aggressiveness," said Dr. Carlo Gambacorti-Passerini, who presented the adult findings June 17 at the annual congress of the European Hematology Association. These data give a strong signal that further investigation in ALK-positive lymphomas is warranted.

Crizotinib was approved by the Food and Drug Administration for the treatment of ALK-driven non–small cell lung cancer (NSCLC) last August, but these new data suggest that responses may be even better in these lymphoma patients.

"It looks like, compared to EMF4-ALK-positive non–small cell lung cancer, the responses are much more durable," observed Dr. Matthias Theobald of Medizinische Klinik und Poliklink in Mainz, Germany, who chaired the session in which the adult findings were presented.

"Why lung cancer patients only have a median duration of responses of 10-12 months is not very clear," responded Dr. Carlo Gambacorti-Passerini, professor of internal medicine at the University of Milan–Bicocca and director of the clinical research unit at S. Gerardo Hospital, both in Monza, Italy.

It is also not apparent why some patients with ALK-positive lymphoma initially benefit while others develop resistance with time. "The main issue here is that [nearly] everybody responds, but after 2-3 months we see a divide," Dr. Gambacorti-Passerini said.

Four men and five women aged between 20 and 56 years (median age, 31 years) received crizotinib at a dose of 250 mg twice daily as part of a compassionate protocol. Seven patients had ALCL, and two patients had diffuse large cell lymphoma according to WHO criteria.

The median number of previous lines of therapy they had collectively received was three, although some had received up to five prior chemotherapy regimens, three had undergone autologous bone marrow transplant, and one patient an allogenic bone marrow transplant. While on crizotinib, steroid use or the use of drugs with antineoplastic activity was not allowed.

The effects of crizotinib were carefully assessed via physical exam, examination of bone marrow aspirate, positron-emission tomography and computed tomography scans, and blood tests before treatment initiation and at monthly intervals for the first 3 months, then every 3 months for up to 2 years. Disease status was also evaluated according to standard RECIST criteria.

After a median follow-up of 8 months, six patients had achieved a complete response to crizotinib, lasting for 2, 5, 8, 13, 18, or 24 months or more, respectively. A further two patients had a partial response.

Dr. Gambacorti-Passerini reported responses to treatment were "very rapid," with alleviation of fever within 2-10 days and time to normalization of serum lactate dehydrogenase within a month.

Furthermore, three patients were still on treatment with crizotinib. Six patients had discontinued: one because of patient request and five because of disease progression. The patient who discontinued by request did so because of severe gastroparesis unrelated to crizotinib and after a planned stoppage of the drug for a stem cell transplant.

Importantly, overall survival at 24 months appears to be just over 40%.

The most common side effects and lab abnormalities were ocular flashes, which all nine patients experienced, but these were of grade 1 or 2 and usually a temporary effect; one patient each had a grade 1-2 peripheral edema, a grade 3 neutropenia, and a grade 2 liver function test abnormality.

"These data show that crizotinib was well tolerated in this population of heavily pretreated patients," Dr. Gambacorti-Passerini concluded. He noted that patients have been treated with crizotinib for 2 years or more, which is the longest anyone has received the drug.

"Now, crizotinib is being evaluated in a registration study, which will start after this compassionate use," he added. This international phase I study (NCT01121588) is currently enrolling patients, and there are also suggestions of using crizotinib as first-line treatment or in combination with other agents for ALK+ lymphomas.

Dr. Gambacorti-Passerini has received research funding from Pfizer, which supported the compassionate use program.

AMSTERDAM – Crizotinib has shown significant antitumor activity in adult patients with lymphomas that express the anaplastic lymphoma kinase gene and who were resistant to the effects of at least three lines of previous therapy.

During a compassionate use program, eight of nine patients with anaplastic lymphoma kinase (ALK)–positive lymphoma responded to crizotinib (Xalkori). Six patients had complete responses, and four achieved durable responses lasting more than 6 months.

Sara Freeman/IMNG Medical Media

These data mirror positive early results already seen in pediatric anaplastic large cell lymphoma (ALCL). Seven of eight children treated with crizotinib had complete and durable responses, investigators reported at the American Society of Clinical Oncology annual meeting.

"Clinically, ALK+ lymphomas are known for their aggressiveness," said Dr. Carlo Gambacorti-Passerini, who presented the adult findings June 17 at the annual congress of the European Hematology Association. These data give a strong signal that further investigation in ALK-positive lymphomas is warranted.

Crizotinib was approved by the Food and Drug Administration for the treatment of ALK-driven non–small cell lung cancer (NSCLC) last August, but these new data suggest that responses may be even better in these lymphoma patients.

"It looks like, compared to EMF4-ALK-positive non–small cell lung cancer, the responses are much more durable," observed Dr. Matthias Theobald of Medizinische Klinik und Poliklink in Mainz, Germany, who chaired the session in which the adult findings were presented.

"Why lung cancer patients only have a median duration of responses of 10-12 months is not very clear," responded Dr. Carlo Gambacorti-Passerini, professor of internal medicine at the University of Milan–Bicocca and director of the clinical research unit at S. Gerardo Hospital, both in Monza, Italy.

It is also not apparent why some patients with ALK-positive lymphoma initially benefit while others develop resistance with time. "The main issue here is that [nearly] everybody responds, but after 2-3 months we see a divide," Dr. Gambacorti-Passerini said.

Four men and five women aged between 20 and 56 years (median age, 31 years) received crizotinib at a dose of 250 mg twice daily as part of a compassionate protocol. Seven patients had ALCL, and two patients had diffuse large cell lymphoma according to WHO criteria.

The median number of previous lines of therapy they had collectively received was three, although some had received up to five prior chemotherapy regimens, three had undergone autologous bone marrow transplant, and one patient an allogenic bone marrow transplant. While on crizotinib, steroid use or the use of drugs with antineoplastic activity was not allowed.

The effects of crizotinib were carefully assessed via physical exam, examination of bone marrow aspirate, positron-emission tomography and computed tomography scans, and blood tests before treatment initiation and at monthly intervals for the first 3 months, then every 3 months for up to 2 years. Disease status was also evaluated according to standard RECIST criteria.

After a median follow-up of 8 months, six patients had achieved a complete response to crizotinib, lasting for 2, 5, 8, 13, 18, or 24 months or more, respectively. A further two patients had a partial response.

Dr. Gambacorti-Passerini reported responses to treatment were "very rapid," with alleviation of fever within 2-10 days and time to normalization of serum lactate dehydrogenase within a month.

Furthermore, three patients were still on treatment with crizotinib. Six patients had discontinued: one because of patient request and five because of disease progression. The patient who discontinued by request did so because of severe gastroparesis unrelated to crizotinib and after a planned stoppage of the drug for a stem cell transplant.

Importantly, overall survival at 24 months appears to be just over 40%.

The most common side effects and lab abnormalities were ocular flashes, which all nine patients experienced, but these were of grade 1 or 2 and usually a temporary effect; one patient each had a grade 1-2 peripheral edema, a grade 3 neutropenia, and a grade 2 liver function test abnormality.

"These data show that crizotinib was well tolerated in this population of heavily pretreated patients," Dr. Gambacorti-Passerini concluded. He noted that patients have been treated with crizotinib for 2 years or more, which is the longest anyone has received the drug.

"Now, crizotinib is being evaluated in a registration study, which will start after this compassionate use," he added. This international phase I study (NCT01121588) is currently enrolling patients, and there are also suggestions of using crizotinib as first-line treatment or in combination with other agents for ALK+ lymphomas.

Dr. Gambacorti-Passerini has received research funding from Pfizer, which supported the compassionate use program.