Non-Hodgkin Lymphoma Hub

Adult lymphoma survivors who were treated with autologous hematopoietic stem-cell transplantation had a greater than sixfold increased risk of left ventricular systolic dysfunction compared with controls, according to a study published online in the Journal of Clinical Oncology.

Among 274 adult survivors of Hodgkin or non-Hodgkin lymphoma, 16% had left ventricular systolic dysfunction (LVSD): 11% had overt heart failure (HF) and 5% had asymptomatic LVSD, defined as a left ventricular ejection fraction of less than 50%.Heart symptoms were significantly associated with exposure to doxorubicin at a cumulative dose of 300 mg/m² or more and with cardiac radiation therapy of more than 30 Gy. Recognizing these patient risk factors allows for more intensive follow-up with the goal of “identification and early treatment of asymptomatic LVSD [which] may prevent the development of HF,” wrote Dr. Klaus Murbraech of Oslo University Hospital and his colleagues (J. Clin. Oncol. 2015 July 13 [doi:10.1200/JCO.2015.60.8125]).

The investigators observed no association between lower-dose cardiac radiation therapy and LVSD. There was only a marginally significant association between the presence of two or more traditional cardiovascular disease risk factors and LVSD.

The cross-sectional multicenter cohort study is the first to assess the prevalence of LVSD, according to Dr. Murbraech and his colleagues. The study included adult survivors of Hodgkin or non-Hodgkin lymphoma, median age 56 years, who underwent autologous stem-cell transplants in Norway from 1987 to 2008. The median observation time was 13 years (range, 4-34 years). The control group consisted of initially healthy patients in an echocardiographic follow-up study. Controls were matched to patients based on age, sex, systolic blood pressure, and body mass index.

The study was supported by the South-Eastern Norway Regional Health Authority and Extrastiftelsen. Dr. Murbraech reported having no disclosures.

Adult lymphoma survivors who were treated with autologous hematopoietic stem-cell transplantation had a greater than sixfold increased risk of left ventricular systolic dysfunction compared with controls, according to a study published online in the Journal of Clinical Oncology.

Among 274 adult survivors of Hodgkin or non-Hodgkin lymphoma, 16% had left ventricular systolic dysfunction (LVSD): 11% had overt heart failure (HF) and 5% had asymptomatic LVSD, defined as a left ventricular ejection fraction of less than 50%.Heart symptoms were significantly associated with exposure to doxorubicin at a cumulative dose of 300 mg/m² or more and with cardiac radiation therapy of more than 30 Gy. Recognizing these patient risk factors allows for more intensive follow-up with the goal of “identification and early treatment of asymptomatic LVSD [which] may prevent the development of HF,” wrote Dr. Klaus Murbraech of Oslo University Hospital and his colleagues (J. Clin. Oncol. 2015 July 13 [doi:10.1200/JCO.2015.60.8125]).

The investigators observed no association between lower-dose cardiac radiation therapy and LVSD. There was only a marginally significant association between the presence of two or more traditional cardiovascular disease risk factors and LVSD.

The cross-sectional multicenter cohort study is the first to assess the prevalence of LVSD, according to Dr. Murbraech and his colleagues. The study included adult survivors of Hodgkin or non-Hodgkin lymphoma, median age 56 years, who underwent autologous stem-cell transplants in Norway from 1987 to 2008. The median observation time was 13 years (range, 4-34 years). The control group consisted of initially healthy patients in an echocardiographic follow-up study. Controls were matched to patients based on age, sex, systolic blood pressure, and body mass index.

The study was supported by the South-Eastern Norway Regional Health Authority and Extrastiftelsen. Dr. Murbraech reported having no disclosures.

Adult lymphoma survivors who were treated with autologous hematopoietic stem-cell transplantation had a greater than sixfold increased risk of left ventricular systolic dysfunction compared with controls, according to a study published online in the Journal of Clinical Oncology.

Among 274 adult survivors of Hodgkin or non-Hodgkin lymphoma, 16% had left ventricular systolic dysfunction (LVSD): 11% had overt heart failure (HF) and 5% had asymptomatic LVSD, defined as a left ventricular ejection fraction of less than 50%.Heart symptoms were significantly associated with exposure to doxorubicin at a cumulative dose of 300 mg/m² or more and with cardiac radiation therapy of more than 30 Gy. Recognizing these patient risk factors allows for more intensive follow-up with the goal of “identification and early treatment of asymptomatic LVSD [which] may prevent the development of HF,” wrote Dr. Klaus Murbraech of Oslo University Hospital and his colleagues (J. Clin. Oncol. 2015 July 13 [doi:10.1200/JCO.2015.60.8125]).

The investigators observed no association between lower-dose cardiac radiation therapy and LVSD. There was only a marginally significant association between the presence of two or more traditional cardiovascular disease risk factors and LVSD.

The cross-sectional multicenter cohort study is the first to assess the prevalence of LVSD, according to Dr. Murbraech and his colleagues. The study included adult survivors of Hodgkin or non-Hodgkin lymphoma, median age 56 years, who underwent autologous stem-cell transplants in Norway from 1987 to 2008. The median observation time was 13 years (range, 4-34 years). The control group consisted of initially healthy patients in an echocardiographic follow-up study. Controls were matched to patients based on age, sex, systolic blood pressure, and body mass index.

The study was supported by the South-Eastern Norway Regional Health Authority and Extrastiftelsen. Dr. Murbraech reported having no disclosures.

Bleomycin can be eliminated after two cycles of the ABVD chemotherapeutic regimen based on a negative interim PET scan finding in patients with Hodgkin lymphoma, according to the 3-year findings of the RATHL study.

Being able to omit bleomycin after a negative interim PET scan was associated with a lower rate of pulmonary toxicity, but no loss in efficacy. For patients with positive interim PET scans, a more aggressive therapy was associated with good outcomes, suggesting that response-adapted therapy can yield good results, Dr. Peter Johnson said at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

In the large international RATHL study (Response-Adapted Therapy in Hodgkin Lymphoma study) 1,137 adults with newly diagnosed disease (41% stage II, 31% stage III, 28% stage IV) underwent PET-CT scans at baseline and after completing two cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). The patients’ PET images were centrally reviewed using a 5-point scale as either negative (1-3) or positive (4-5),

The majority of patients (84%) had negative scans after two cycles of the ABVD regimen and were randomized to receive four additional cycles either with or without bleomycin (ABVD or AVD). Consolidation radiotherapy was not advised for patients whose interim PET scans were negative, regardless of baseline bulk or residual masses, Dr. Johnson, of the Cancer Research UK Centre at University of Southampton, England, reported.

Patients with positive interim PET scans received escalated therapy with a BEACOPP (bleomycin, etoposide, doxorubicin [Adriamycin], cyclophosphamide, vincristine [Oncovin], procarbazine, prednisolone) regimen. They received either eBEACOPP and BEASCOPP-14.

At the 3-year follow-up, progression-free survival in the PET-negative group was 85% for both the ABVD- and AVD-treated patients. Similarly, overall survival was 97% for both groups.

Factors that predicted treatment failure after a negative interim PET scan were initial tumor stage and international prognostic score, but not bulk, B symptoms, or score of the interim PET scan.

ABVD was associated with more pulmonary toxicity than was AVD.

Of 174 patients who had a positive interim PET scan and received escalated therapy, 74% had a subsequent negative PET scan after treatment. Their 3-year, progression-free survival rate was 68%, and their overall survival was 86% with no difference in outcome between two variations of BEACOPP (eBEACOPP and BEASCOPP-14).

Of the 53 deaths in the study, 19 were caused by Hodgkin lymphoma. The overall 3-year progression-free survival is 83%, and overall survival is 95%.

The results of the RATHL study have important implications for therapy of Hodgkin lymphoma, Dr. Johnson stated. First, interim PET scans are highly predictive for response to ABVD, providing valuable prognostic information to support decisions related to escalation of therapy. Secondly, after two cycles of ABVD, “it is safe to omit bleomycin from subsequent cycles, without consolidation radiotherapy,” he reported.

Omitting bleomycin has the potential to reduce pulmonary toxicity from chemotherapy, especially dyspnea, thromboembolism, and neutropenic fever, Dr. Johnson added. In the RATHL study, rates of pulmonary toxicity were significantly higher in the group receiving bleomycin.

Bleomycin can be eliminated after two cycles of the ABVD chemotherapeutic regimen based on a negative interim PET scan finding in patients with Hodgkin lymphoma, according to the 3-year findings of the RATHL study.

Being able to omit bleomycin after a negative interim PET scan was associated with a lower rate of pulmonary toxicity, but no loss in efficacy. For patients with positive interim PET scans, a more aggressive therapy was associated with good outcomes, suggesting that response-adapted therapy can yield good results, Dr. Peter Johnson said at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

In the large international RATHL study (Response-Adapted Therapy in Hodgkin Lymphoma study) 1,137 adults with newly diagnosed disease (41% stage II, 31% stage III, 28% stage IV) underwent PET-CT scans at baseline and after completing two cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). The patients’ PET images were centrally reviewed using a 5-point scale as either negative (1-3) or positive (4-5),

The majority of patients (84%) had negative scans after two cycles of the ABVD regimen and were randomized to receive four additional cycles either with or without bleomycin (ABVD or AVD). Consolidation radiotherapy was not advised for patients whose interim PET scans were negative, regardless of baseline bulk or residual masses, Dr. Johnson, of the Cancer Research UK Centre at University of Southampton, England, reported.

Patients with positive interim PET scans received escalated therapy with a BEACOPP (bleomycin, etoposide, doxorubicin [Adriamycin], cyclophosphamide, vincristine [Oncovin], procarbazine, prednisolone) regimen. They received either eBEACOPP and BEASCOPP-14.

At the 3-year follow-up, progression-free survival in the PET-negative group was 85% for both the ABVD- and AVD-treated patients. Similarly, overall survival was 97% for both groups.

Factors that predicted treatment failure after a negative interim PET scan were initial tumor stage and international prognostic score, but not bulk, B symptoms, or score of the interim PET scan.

ABVD was associated with more pulmonary toxicity than was AVD.

Of 174 patients who had a positive interim PET scan and received escalated therapy, 74% had a subsequent negative PET scan after treatment. Their 3-year, progression-free survival rate was 68%, and their overall survival was 86% with no difference in outcome between two variations of BEACOPP (eBEACOPP and BEASCOPP-14).

Of the 53 deaths in the study, 19 were caused by Hodgkin lymphoma. The overall 3-year progression-free survival is 83%, and overall survival is 95%.

The results of the RATHL study have important implications for therapy of Hodgkin lymphoma, Dr. Johnson stated. First, interim PET scans are highly predictive for response to ABVD, providing valuable prognostic information to support decisions related to escalation of therapy. Secondly, after two cycles of ABVD, “it is safe to omit bleomycin from subsequent cycles, without consolidation radiotherapy,” he reported.

Omitting bleomycin has the potential to reduce pulmonary toxicity from chemotherapy, especially dyspnea, thromboembolism, and neutropenic fever, Dr. Johnson added. In the RATHL study, rates of pulmonary toxicity were significantly higher in the group receiving bleomycin.

Bleomycin can be eliminated after two cycles of the ABVD chemotherapeutic regimen based on a negative interim PET scan finding in patients with Hodgkin lymphoma, according to the 3-year findings of the RATHL study.

Being able to omit bleomycin after a negative interim PET scan was associated with a lower rate of pulmonary toxicity, but no loss in efficacy. For patients with positive interim PET scans, a more aggressive therapy was associated with good outcomes, suggesting that response-adapted therapy can yield good results, Dr. Peter Johnson said at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

In the large international RATHL study (Response-Adapted Therapy in Hodgkin Lymphoma study) 1,137 adults with newly diagnosed disease (41% stage II, 31% stage III, 28% stage IV) underwent PET-CT scans at baseline and after completing two cycles of ABVD (adriamycin, bleomycin, vinblastine, dacarbazine). The patients’ PET images were centrally reviewed using a 5-point scale as either negative (1-3) or positive (4-5),

The majority of patients (84%) had negative scans after two cycles of the ABVD regimen and were randomized to receive four additional cycles either with or without bleomycin (ABVD or AVD). Consolidation radiotherapy was not advised for patients whose interim PET scans were negative, regardless of baseline bulk or residual masses, Dr. Johnson, of the Cancer Research UK Centre at University of Southampton, England, reported.

Patients with positive interim PET scans received escalated therapy with a BEACOPP (bleomycin, etoposide, doxorubicin [Adriamycin], cyclophosphamide, vincristine [Oncovin], procarbazine, prednisolone) regimen. They received either eBEACOPP and BEASCOPP-14.

At the 3-year follow-up, progression-free survival in the PET-negative group was 85% for both the ABVD- and AVD-treated patients. Similarly, overall survival was 97% for both groups.

Factors that predicted treatment failure after a negative interim PET scan were initial tumor stage and international prognostic score, but not bulk, B symptoms, or score of the interim PET scan.

ABVD was associated with more pulmonary toxicity than was AVD.

Of 174 patients who had a positive interim PET scan and received escalated therapy, 74% had a subsequent negative PET scan after treatment. Their 3-year, progression-free survival rate was 68%, and their overall survival was 86% with no difference in outcome between two variations of BEACOPP (eBEACOPP and BEASCOPP-14).

Of the 53 deaths in the study, 19 were caused by Hodgkin lymphoma. The overall 3-year progression-free survival is 83%, and overall survival is 95%.

The results of the RATHL study have important implications for therapy of Hodgkin lymphoma, Dr. Johnson stated. First, interim PET scans are highly predictive for response to ABVD, providing valuable prognostic information to support decisions related to escalation of therapy. Secondly, after two cycles of ABVD, “it is safe to omit bleomycin from subsequent cycles, without consolidation radiotherapy,” he reported.

Omitting bleomycin has the potential to reduce pulmonary toxicity from chemotherapy, especially dyspnea, thromboembolism, and neutropenic fever, Dr. Johnson added. In the RATHL study, rates of pulmonary toxicity were significantly higher in the group receiving bleomycin.

Results from positron emission tomography after 2 and 4 weeks of standardized, dose-dense chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) failed to provide sufficient prognostic accuracy to guide therapeutic decisions, according to a report published online in the Journal of Clinical Oncology.

“Our data demonstrate that interim PET-CT fails to deliver a PPV [positive predictive value] or NPV [negative predictive value] that reflects the clinical outcome for patients with DLBCL treated with R-CHOP-14 with sufficient accuracy to guide therapeutic decisions such as treatment intensification/deintensification at the present stage,” wrote Dr. Chrisoph Mamot of the division of haematology/oncology, Cantonal Hospital of Aarau, Switzerland, and colleagues (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.58.9846]).

Although the likelihood of 2-year event-free survival (EFS) was significantly lower among patients who had positive PET results after 2 weeks of therapy (PET-2-positive), compared with PET-2-negative patients (48% vs. 74%; P = .004), a large proportion of interim PET-positive patients had favorable outcomes. This may be due to the dose-dense regimen, Dr. Mamot and colleagues said.

Patients underwent six cycles of R-CHOP (rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², vincristine 1.4 mg/m², and prednisone 100 mg/m² for 5 days) every 14 days, followed by two cycles of rituximab.

Patients who had a positive PET-2 result received another PET scan after completion of four chemotherapy cycles. The 2-year EFS for PET-4-positive and PET-4-negative patients were not significantly different.

“Our original hypothesis that an interim PET/CT at a later time point might be able to better separate patients with good or poor prognosis was not confirmed,” the authors wrote. The end-of-treatment PET provided the best prediction of good vs. poor prognosis, but this time point is too late to adapt treatment. The authors concluded that interim PET/CT in patients with DLBCL presently is not accurate enough to guide treatment decisions in individual patients.

The multicenter, prospective study evaluated 138 patients, median age 58.5 years, who had untreated DLBCL, Ann Arbor stage I (12%), II (34%), III (23%), or IV (30%).

The study was supported by grants from Amgen (Switzerland) and OncoSuisse. Dr. Christoph Mamot reported consulting or advisory roles with Roche, Novartis, Amgen, and Boehringer-Ingelheim. Several of his coauthors reported ties to industry sources.


Results from positron emission tomography after 2 and 4 weeks of standardized, dose-dense chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) failed to provide sufficient prognostic accuracy to guide therapeutic decisions, according to a report published online in the Journal of Clinical Oncology.

“Our data demonstrate that interim PET-CT fails to deliver a PPV [positive predictive value] or NPV [negative predictive value] that reflects the clinical outcome for patients with DLBCL treated with R-CHOP-14 with sufficient accuracy to guide therapeutic decisions such as treatment intensification/deintensification at the present stage,” wrote Dr. Chrisoph Mamot of the division of haematology/oncology, Cantonal Hospital of Aarau, Switzerland, and colleagues (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.58.9846]).

Although the likelihood of 2-year event-free survival (EFS) was significantly lower among patients who had positive PET results after 2 weeks of therapy (PET-2-positive), compared with PET-2-negative patients (48% vs. 74%; P = .004), a large proportion of interim PET-positive patients had favorable outcomes. This may be due to the dose-dense regimen, Dr. Mamot and colleagues said.

Patients underwent six cycles of R-CHOP (rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², vincristine 1.4 mg/m², and prednisone 100 mg/m² for 5 days) every 14 days, followed by two cycles of rituximab.

Patients who had a positive PET-2 result received another PET scan after completion of four chemotherapy cycles. The 2-year EFS for PET-4-positive and PET-4-negative patients were not significantly different.

“Our original hypothesis that an interim PET/CT at a later time point might be able to better separate patients with good or poor prognosis was not confirmed,” the authors wrote. The end-of-treatment PET provided the best prediction of good vs. poor prognosis, but this time point is too late to adapt treatment. The authors concluded that interim PET/CT in patients with DLBCL presently is not accurate enough to guide treatment decisions in individual patients.

The multicenter, prospective study evaluated 138 patients, median age 58.5 years, who had untreated DLBCL, Ann Arbor stage I (12%), II (34%), III (23%), or IV (30%).

The study was supported by grants from Amgen (Switzerland) and OncoSuisse. Dr. Christoph Mamot reported consulting or advisory roles with Roche, Novartis, Amgen, and Boehringer-Ingelheim. Several of his coauthors reported ties to industry sources.


Results from positron emission tomography after 2 and 4 weeks of standardized, dose-dense chemotherapy in patients with diffuse large B-cell lymphoma (DLBCL) failed to provide sufficient prognostic accuracy to guide therapeutic decisions, according to a report published online in the Journal of Clinical Oncology.

“Our data demonstrate that interim PET-CT fails to deliver a PPV [positive predictive value] or NPV [negative predictive value] that reflects the clinical outcome for patients with DLBCL treated with R-CHOP-14 with sufficient accuracy to guide therapeutic decisions such as treatment intensification/deintensification at the present stage,” wrote Dr. Chrisoph Mamot of the division of haematology/oncology, Cantonal Hospital of Aarau, Switzerland, and colleagues (J. Clin. Onc. 2015 July 6 [doi:10.1200/JCO.2014.58.9846]).

Although the likelihood of 2-year event-free survival (EFS) was significantly lower among patients who had positive PET results after 2 weeks of therapy (PET-2-positive), compared with PET-2-negative patients (48% vs. 74%; P = .004), a large proportion of interim PET-positive patients had favorable outcomes. This may be due to the dose-dense regimen, Dr. Mamot and colleagues said.

Patients underwent six cycles of R-CHOP (rituximab 375 mg/m², cyclophosphamide 750 mg/m², doxorubicin 50 mg/m², vincristine 1.4 mg/m², and prednisone 100 mg/m² for 5 days) every 14 days, followed by two cycles of rituximab.

Patients who had a positive PET-2 result received another PET scan after completion of four chemotherapy cycles. The 2-year EFS for PET-4-positive and PET-4-negative patients were not significantly different.

“Our original hypothesis that an interim PET/CT at a later time point might be able to better separate patients with good or poor prognosis was not confirmed,” the authors wrote. The end-of-treatment PET provided the best prediction of good vs. poor prognosis, but this time point is too late to adapt treatment. The authors concluded that interim PET/CT in patients with DLBCL presently is not accurate enough to guide treatment decisions in individual patients.

The multicenter, prospective study evaluated 138 patients, median age 58.5 years, who had untreated DLBCL, Ann Arbor stage I (12%), II (34%), III (23%), or IV (30%).

The study was supported by grants from Amgen (Switzerland) and OncoSuisse. Dr. Christoph Mamot reported consulting or advisory roles with Roche, Novartis, Amgen, and Boehringer-Ingelheim. Several of his coauthors reported ties to industry sources.


In patients with newly diagnosed lymphoma and suspected lymphoma, a second pathological review found inaccuracies in the original diagnosis among 17% of more than 42,000 cases, based on data presented at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

In more than 25% of all discrepancies, tumors were reclassified at the second pathology review as the result of findings from additional immunostaining and molecular studies – polymerase chain reaction and fluorescence in situ hybridization.

In 15% of cases, diagnostic changes were expected to result in a change in patient management.

“Our study highlights the importance of specialized centralized review of lymphoma diagnosis, not only in the setting of clinical trials but also in routine clinical practice, for optimal patient management,” reported Dr. Camille Laurent of the Institut Universitaire du Cancer Oncopole, Toulouse, France.

In 2010, the French National Cancer Agency (INCa) established the Lymphopath Network, comprising 33 reference centers, to provide a review by expert hematopathologists of every newly diagnosed lymphoma or suspected lymphoma prior to treatment. These new diagnoses were entered in a central national database. Between 2010 and 2015, 42,146 samples were reviewed: 35,753 were newly diagnosed as lymphomas, while the remaining 6,393 cases included 4,610 reactive lymphoid conditions and 1,783 nonlymphoid malignancies, including especially myeloma and leukemic disorders.

Discordant diagnoses among extra-cutaneous lymphomas were carefully examined by a hematologist and recorded as major or minor depending on the expected therapeutic impact. Dr. Laurent said.

The discordance rate between the referral diagnosis and the final diagnosis was 17.2%. Small B-cell lymphomas and peripheral T-cell lymphoma subtyping were the most common discrepancies; 6.4% of discordances were due to an unspecified lymphoma diagnosis, Dr. Laurent stated.

Less than 2% of discrepancies were due to misclassifications of benign versus malignant lymphoid conditions and of Hodgkin lymphoma versus non-Hodgkin lymphoma. There were minor discrepancies (2.2%) in follicular lymphoma misgrading and diffuse large B-cell lymphoma subtypes.

In patients with newly diagnosed lymphoma and suspected lymphoma, a second pathological review found inaccuracies in the original diagnosis among 17% of more than 42,000 cases, based on data presented at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

In more than 25% of all discrepancies, tumors were reclassified at the second pathology review as the result of findings from additional immunostaining and molecular studies – polymerase chain reaction and fluorescence in situ hybridization.

In 15% of cases, diagnostic changes were expected to result in a change in patient management.

“Our study highlights the importance of specialized centralized review of lymphoma diagnosis, not only in the setting of clinical trials but also in routine clinical practice, for optimal patient management,” reported Dr. Camille Laurent of the Institut Universitaire du Cancer Oncopole, Toulouse, France.

In 2010, the French National Cancer Agency (INCa) established the Lymphopath Network, comprising 33 reference centers, to provide a review by expert hematopathologists of every newly diagnosed lymphoma or suspected lymphoma prior to treatment. These new diagnoses were entered in a central national database. Between 2010 and 2015, 42,146 samples were reviewed: 35,753 were newly diagnosed as lymphomas, while the remaining 6,393 cases included 4,610 reactive lymphoid conditions and 1,783 nonlymphoid malignancies, including especially myeloma and leukemic disorders.

Discordant diagnoses among extra-cutaneous lymphomas were carefully examined by a hematologist and recorded as major or minor depending on the expected therapeutic impact. Dr. Laurent said.

The discordance rate between the referral diagnosis and the final diagnosis was 17.2%. Small B-cell lymphomas and peripheral T-cell lymphoma subtyping were the most common discrepancies; 6.4% of discordances were due to an unspecified lymphoma diagnosis, Dr. Laurent stated.

Less than 2% of discrepancies were due to misclassifications of benign versus malignant lymphoid conditions and of Hodgkin lymphoma versus non-Hodgkin lymphoma. There were minor discrepancies (2.2%) in follicular lymphoma misgrading and diffuse large B-cell lymphoma subtypes.

In patients with newly diagnosed lymphoma and suspected lymphoma, a second pathological review found inaccuracies in the original diagnosis among 17% of more than 42,000 cases, based on data presented at the International Congress on Malignant Lymphoma in Lugano, Switzerland.

In more than 25% of all discrepancies, tumors were reclassified at the second pathology review as the result of findings from additional immunostaining and molecular studies – polymerase chain reaction and fluorescence in situ hybridization.

In 15% of cases, diagnostic changes were expected to result in a change in patient management.

“Our study highlights the importance of specialized centralized review of lymphoma diagnosis, not only in the setting of clinical trials but also in routine clinical practice, for optimal patient management,” reported Dr. Camille Laurent of the Institut Universitaire du Cancer Oncopole, Toulouse, France.

In 2010, the French National Cancer Agency (INCa) established the Lymphopath Network, comprising 33 reference centers, to provide a review by expert hematopathologists of every newly diagnosed lymphoma or suspected lymphoma prior to treatment. These new diagnoses were entered in a central national database. Between 2010 and 2015, 42,146 samples were reviewed: 35,753 were newly diagnosed as lymphomas, while the remaining 6,393 cases included 4,610 reactive lymphoid conditions and 1,783 nonlymphoid malignancies, including especially myeloma and leukemic disorders.

Discordant diagnoses among extra-cutaneous lymphomas were carefully examined by a hematologist and recorded as major or minor depending on the expected therapeutic impact. Dr. Laurent said.

The discordance rate between the referral diagnosis and the final diagnosis was 17.2%. Small B-cell lymphomas and peripheral T-cell lymphoma subtyping were the most common discrepancies; 6.4% of discordances were due to an unspecified lymphoma diagnosis, Dr. Laurent stated.

Less than 2% of discrepancies were due to misclassifications of benign versus malignant lymphoid conditions and of Hodgkin lymphoma versus non-Hodgkin lymphoma. There were minor discrepancies (2.2%) in follicular lymphoma misgrading and diffuse large B-cell lymphoma subtypes.

VIENNA – The investigational dual HDAC and Pi3K inhibitor CUDC-907 was reasonably tolerated and clinically active in a phase I study of relapsed or refractory lymphomas and multiple myeloma.

Among 44 patients evaluable for response, 7 had objective responses (16%).

Two complete and four partial responses occurred in 10 evaluable patients with diffuse large B-cell lymphoma (DLBCL).

One partial response was reported in 12 evaluable patients with Hodgkin lymphoma.

Stable disease was the best response in 4 of 6 evaluable patients with multiple myeloma and 11 of 16 patients with other lymphomas, Dr. Yasuhiro Oki reported at the annual congress of the European Hematology Association.

The first-in-human trial enrolled 57 patients with lymphoma (DLBCL, Hodgkin, Burkitt, follicular, gray zone, lymphoplasmacytic, mantle cell, marginal zone, and small lymphocytic) or multiple myeloma that was refractory to or relapsed after at least two prior regimens.

The median number of prior regimens was 5 (range 2-10), including prior histone deacetylase (HDAC) inhibitors in 11% and prior phosphatidylinositol 3-kinase (Pi3K) inhibitors in 9%.

The 3+3 design tested three different once-daily dosing schedules for the oral small molecule: 30 mg and 60 mg, 5 days on and 2 days off (5/2) 60 mg, and intermittent twice- or thrice-weekly at 60 mg, 90 mg, 120 mg, and 150 mg. The safety and efficacy data are from the completed dose escalation and ongoing expansion stages of the phase I trial with CUDC-907 administered as monotherapy.

Median treatment duration in the DLBCL group was 3 months, with treatment ongoing in some patients beyond 2 years. Long-term responders have included three patients with transformed follicular lymphoma (t-FL)/DLBCL, one with so-called triple-hit status involving translocations/rearrangements of MYC, BCL-2, and BCL-6 genes, according to Dr. Oki of University of Texas MD Anderson Cancer Center in Houston.

The patient with Hodgkin lymphoma who responded had failed four prior therapies, but experienced a 42% reduction in tumor size on imaging by cycle two and a partial response to 60 mg 5/2 CUDC-907 by cycle six.

At least one adverse event (AE) occurred in 50 of the 57 patients, but AEs have been reversible with standard interventions, dose holds, or dose reductions, he added.

The most common grade 3/4 AEs reported in two or more patients were diarrhea, hyperglycemia, fatigue, thrombocytopenia, and decreased neutrophils.

Four dose-limiting toxicities occurred in three patients: grade 3 diarrhea in the 60-mg once-daily and 150-mg thrice-weekly dose groups and grade 4 hyperglycemia in the 60-mg once-daily and 150-mg twice-weekly dose groups.

“The 5/2 60-mg and thrice-weekly 120-mg dosing was found to be reasonably tolerated while still achieving objective responses,” Dr. Oki noted in the poster.

The ongoing expansion phase is evaluating CUDC-907 at the recommended phase II doses of 60 mg 5/2 and 120 mg thrice-weekly in patients with relapsed refractory DLBCL, Hodgkin lymphoma, and multiple myeloma.

The trial is currently enrolling patients with DLBCL for treatment with CUDC-907 monotherapy and in combination with standard-dose rituximab.

Phase II testing of CUDC-907 in combination with rituximab in relapsed/refractory DLBCL is projected to start at the earliest in fourth-quarter 2015, according to the authors.

CUDC-907 (60 mg 5/2 and 120 mg three times weekly) is also being evaluated in advanced or relapsed solid tumors in an ongoing phase I trial.

pwendling@frontlinemedcom.com

On Twitter@pwendl

VIENNA – The investigational dual HDAC and Pi3K inhibitor CUDC-907 was reasonably tolerated and clinically active in a phase I study of relapsed or refractory lymphomas and multiple myeloma.

Among 44 patients evaluable for response, 7 had objective responses (16%).

Two complete and four partial responses occurred in 10 evaluable patients with diffuse large B-cell lymphoma (DLBCL).

One partial response was reported in 12 evaluable patients with Hodgkin lymphoma.

Stable disease was the best response in 4 of 6 evaluable patients with multiple myeloma and 11 of 16 patients with other lymphomas, Dr. Yasuhiro Oki reported at the annual congress of the European Hematology Association.

The first-in-human trial enrolled 57 patients with lymphoma (DLBCL, Hodgkin, Burkitt, follicular, gray zone, lymphoplasmacytic, mantle cell, marginal zone, and small lymphocytic) or multiple myeloma that was refractory to or relapsed after at least two prior regimens.

The median number of prior regimens was 5 (range 2-10), including prior histone deacetylase (HDAC) inhibitors in 11% and prior phosphatidylinositol 3-kinase (Pi3K) inhibitors in 9%.

The 3+3 design tested three different once-daily dosing schedules for the oral small molecule: 30 mg and 60 mg, 5 days on and 2 days off (5/2) 60 mg, and intermittent twice- or thrice-weekly at 60 mg, 90 mg, 120 mg, and 150 mg. The safety and efficacy data are from the completed dose escalation and ongoing expansion stages of the phase I trial with CUDC-907 administered as monotherapy.

Median treatment duration in the DLBCL group was 3 months, with treatment ongoing in some patients beyond 2 years. Long-term responders have included three patients with transformed follicular lymphoma (t-FL)/DLBCL, one with so-called triple-hit status involving translocations/rearrangements of MYC, BCL-2, and BCL-6 genes, according to Dr. Oki of University of Texas MD Anderson Cancer Center in Houston.

The patient with Hodgkin lymphoma who responded had failed four prior therapies, but experienced a 42% reduction in tumor size on imaging by cycle two and a partial response to 60 mg 5/2 CUDC-907 by cycle six.

At least one adverse event (AE) occurred in 50 of the 57 patients, but AEs have been reversible with standard interventions, dose holds, or dose reductions, he added.

The most common grade 3/4 AEs reported in two or more patients were diarrhea, hyperglycemia, fatigue, thrombocytopenia, and decreased neutrophils.

Four dose-limiting toxicities occurred in three patients: grade 3 diarrhea in the 60-mg once-daily and 150-mg thrice-weekly dose groups and grade 4 hyperglycemia in the 60-mg once-daily and 150-mg twice-weekly dose groups.

“The 5/2 60-mg and thrice-weekly 120-mg dosing was found to be reasonably tolerated while still achieving objective responses,” Dr. Oki noted in the poster.

The ongoing expansion phase is evaluating CUDC-907 at the recommended phase II doses of 60 mg 5/2 and 120 mg thrice-weekly in patients with relapsed refractory DLBCL, Hodgkin lymphoma, and multiple myeloma.

The trial is currently enrolling patients with DLBCL for treatment with CUDC-907 monotherapy and in combination with standard-dose rituximab.

Phase II testing of CUDC-907 in combination with rituximab in relapsed/refractory DLBCL is projected to start at the earliest in fourth-quarter 2015, according to the authors.

CUDC-907 (60 mg 5/2 and 120 mg three times weekly) is also being evaluated in advanced or relapsed solid tumors in an ongoing phase I trial.

pwendling@frontlinemedcom.com

On Twitter@pwendl

VIENNA – The investigational dual HDAC and Pi3K inhibitor CUDC-907 was reasonably tolerated and clinically active in a phase I study of relapsed or refractory lymphomas and multiple myeloma.

Among 44 patients evaluable for response, 7 had objective responses (16%).

Two complete and four partial responses occurred in 10 evaluable patients with diffuse large B-cell lymphoma (DLBCL).

One partial response was reported in 12 evaluable patients with Hodgkin lymphoma.

Stable disease was the best response in 4 of 6 evaluable patients with multiple myeloma and 11 of 16 patients with other lymphomas, Dr. Yasuhiro Oki reported at the annual congress of the European Hematology Association.

The first-in-human trial enrolled 57 patients with lymphoma (DLBCL, Hodgkin, Burkitt, follicular, gray zone, lymphoplasmacytic, mantle cell, marginal zone, and small lymphocytic) or multiple myeloma that was refractory to or relapsed after at least two prior regimens.

The median number of prior regimens was 5 (range 2-10), including prior histone deacetylase (HDAC) inhibitors in 11% and prior phosphatidylinositol 3-kinase (Pi3K) inhibitors in 9%.

The 3+3 design tested three different once-daily dosing schedules for the oral small molecule: 30 mg and 60 mg, 5 days on and 2 days off (5/2) 60 mg, and intermittent twice- or thrice-weekly at 60 mg, 90 mg, 120 mg, and 150 mg. The safety and efficacy data are from the completed dose escalation and ongoing expansion stages of the phase I trial with CUDC-907 administered as monotherapy.

Median treatment duration in the DLBCL group was 3 months, with treatment ongoing in some patients beyond 2 years. Long-term responders have included three patients with transformed follicular lymphoma (t-FL)/DLBCL, one with so-called triple-hit status involving translocations/rearrangements of MYC, BCL-2, and BCL-6 genes, according to Dr. Oki of University of Texas MD Anderson Cancer Center in Houston.

The patient with Hodgkin lymphoma who responded had failed four prior therapies, but experienced a 42% reduction in tumor size on imaging by cycle two and a partial response to 60 mg 5/2 CUDC-907 by cycle six.

At least one adverse event (AE) occurred in 50 of the 57 patients, but AEs have been reversible with standard interventions, dose holds, or dose reductions, he added.

The most common grade 3/4 AEs reported in two or more patients were diarrhea, hyperglycemia, fatigue, thrombocytopenia, and decreased neutrophils.

Four dose-limiting toxicities occurred in three patients: grade 3 diarrhea in the 60-mg once-daily and 150-mg thrice-weekly dose groups and grade 4 hyperglycemia in the 60-mg once-daily and 150-mg twice-weekly dose groups.

“The 5/2 60-mg and thrice-weekly 120-mg dosing was found to be reasonably tolerated while still achieving objective responses,” Dr. Oki noted in the poster.

The ongoing expansion phase is evaluating CUDC-907 at the recommended phase II doses of 60 mg 5/2 and 120 mg thrice-weekly in patients with relapsed refractory DLBCL, Hodgkin lymphoma, and multiple myeloma.

The trial is currently enrolling patients with DLBCL for treatment with CUDC-907 monotherapy and in combination with standard-dose rituximab.

Phase II testing of CUDC-907 in combination with rituximab in relapsed/refractory DLBCL is projected to start at the earliest in fourth-quarter 2015, according to the authors.

CUDC-907 (60 mg 5/2 and 120 mg three times weekly) is also being evaluated in advanced or relapsed solid tumors in an ongoing phase I trial.

pwendling@frontlinemedcom.com

On Twitter@pwendl

Patients with follicular lymphoma who relapse within 2 years of receiving R-CHOP chemoimmunotherapy are at high risk of death, unlike those who do not relapse early, according to a report published online in Journal of Clinical Oncology.

Survival in follicular lymphoma, the second most common non-Hodgkin lymphoma in the United States, has dramatically improved over time, and the median survival after first-line chemoimmunotherapy now exceeds 18 years. But researchers have noted a remarkably consistent 20% rate of early relapse across numerous forms of treatment and varied study populations. Until now, the clinical significance of early relapse and its impact on overall survival has not been explored, said Dr. Carla Casulo of the University of Rochester, New York, and her associates.

They examined this issue using data from a national cohort of patients with newly diagnosed follicular lymphoma, focusing on 588 patients with stage II, III, or IV disease who were treated using first-line rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). A total of 19% of these patients relapsed within 24 months of diagnosis. Median follow-up was 7 years. With early disease progression, overall survival was only 68% at 2 years and only 50% at 5 years, compared with 97% and 90%, respectively, among patients who didn’t have early disease progression. Early progression was associated with markedly reduced survival, with a hazard ratio of 7.17.

To verify their findings in a separate cohort, Dr. Casulo and her associates assessed survival in 147 similar patients participating in a different study who were followed for a mean of 5.5 years. A total of 26% of this cohort had early relapse after receiving a variety of first-line chemoimmunotherapy regimens. With early disease progression, overall survival was only 64% at 2 years and only 34% at 5 years, compared with 98% and 94%, respectively, among patients who didn’t have early progression. Again, early progression was associated with markedly reduced survival, with an HR of 20.0 (J. Clin. Oncol. 2015 June 29 [doi: 10.1200/JCO.2014.59.7534]).

These two studies confirm that patients with follicular lymphoma who relapse within 2 years constitute a distinct subgroup at very high risk of death. “Given their poor prognosis, consideration of aggressive second-line treatments, including possibly autologous stem-cell transplantation, seem reasonable,” the investigators said.

Patients with follicular lymphoma who relapse within 2 years of receiving R-CHOP chemoimmunotherapy are at high risk of death, unlike those who do not relapse early, according to a report published online in Journal of Clinical Oncology.

Survival in follicular lymphoma, the second most common non-Hodgkin lymphoma in the United States, has dramatically improved over time, and the median survival after first-line chemoimmunotherapy now exceeds 18 years. But researchers have noted a remarkably consistent 20% rate of early relapse across numerous forms of treatment and varied study populations. Until now, the clinical significance of early relapse and its impact on overall survival has not been explored, said Dr. Carla Casulo of the University of Rochester, New York, and her associates.

They examined this issue using data from a national cohort of patients with newly diagnosed follicular lymphoma, focusing on 588 patients with stage II, III, or IV disease who were treated using first-line rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). A total of 19% of these patients relapsed within 24 months of diagnosis. Median follow-up was 7 years. With early disease progression, overall survival was only 68% at 2 years and only 50% at 5 years, compared with 97% and 90%, respectively, among patients who didn’t have early disease progression. Early progression was associated with markedly reduced survival, with a hazard ratio of 7.17.

To verify their findings in a separate cohort, Dr. Casulo and her associates assessed survival in 147 similar patients participating in a different study who were followed for a mean of 5.5 years. A total of 26% of this cohort had early relapse after receiving a variety of first-line chemoimmunotherapy regimens. With early disease progression, overall survival was only 64% at 2 years and only 34% at 5 years, compared with 98% and 94%, respectively, among patients who didn’t have early progression. Again, early progression was associated with markedly reduced survival, with an HR of 20.0 (J. Clin. Oncol. 2015 June 29 [doi: 10.1200/JCO.2014.59.7534]).

These two studies confirm that patients with follicular lymphoma who relapse within 2 years constitute a distinct subgroup at very high risk of death. “Given their poor prognosis, consideration of aggressive second-line treatments, including possibly autologous stem-cell transplantation, seem reasonable,” the investigators said.

Patients with follicular lymphoma who relapse within 2 years of receiving R-CHOP chemoimmunotherapy are at high risk of death, unlike those who do not relapse early, according to a report published online in Journal of Clinical Oncology.

Survival in follicular lymphoma, the second most common non-Hodgkin lymphoma in the United States, has dramatically improved over time, and the median survival after first-line chemoimmunotherapy now exceeds 18 years. But researchers have noted a remarkably consistent 20% rate of early relapse across numerous forms of treatment and varied study populations. Until now, the clinical significance of early relapse and its impact on overall survival has not been explored, said Dr. Carla Casulo of the University of Rochester, New York, and her associates.

They examined this issue using data from a national cohort of patients with newly diagnosed follicular lymphoma, focusing on 588 patients with stage II, III, or IV disease who were treated using first-line rituximab with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). A total of 19% of these patients relapsed within 24 months of diagnosis. Median follow-up was 7 years. With early disease progression, overall survival was only 68% at 2 years and only 50% at 5 years, compared with 97% and 90%, respectively, among patients who didn’t have early disease progression. Early progression was associated with markedly reduced survival, with a hazard ratio of 7.17.

To verify their findings in a separate cohort, Dr. Casulo and her associates assessed survival in 147 similar patients participating in a different study who were followed for a mean of 5.5 years. A total of 26% of this cohort had early relapse after receiving a variety of first-line chemoimmunotherapy regimens. With early disease progression, overall survival was only 64% at 2 years and only 34% at 5 years, compared with 98% and 94%, respectively, among patients who didn’t have early progression. Again, early progression was associated with markedly reduced survival, with an HR of 20.0 (J. Clin. Oncol. 2015 June 29 [doi: 10.1200/JCO.2014.59.7534]).

These two studies confirm that patients with follicular lymphoma who relapse within 2 years constitute a distinct subgroup at very high risk of death. “Given their poor prognosis, consideration of aggressive second-line treatments, including possibly autologous stem-cell transplantation, seem reasonable,” the investigators said.

CHICAGO – Progression-free survival for patients with rituximab-refractory indolent non-Hodgkin’s lymphomas was effectively doubled with a combination of obinutuzumab and bendamustine, compared with bendamustine alone.

Dr. Laura Helen Sehn from the British Columbia (Canada) Cancer Agency in Vancouver, says that the study, the GADOLIN trial. “is remarkable, because it does demonstrate the first randomized evidence of a clinical benefit of a novel anti-CD20 monoclonal antibiody for patients who are rituximab refractory.”

She described the study’s key findings at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Progression-free survival for patients with rituximab-refractory indolent non-Hodgkin’s lymphomas was effectively doubled with a combination of obinutuzumab and bendamustine, compared with bendamustine alone.

Dr. Laura Helen Sehn from the British Columbia (Canada) Cancer Agency in Vancouver, says that the study, the GADOLIN trial. “is remarkable, because it does demonstrate the first randomized evidence of a clinical benefit of a novel anti-CD20 monoclonal antibiody for patients who are rituximab refractory.”

She described the study’s key findings at the annual meeting of the American Society of Clinical Oncology.

CHICAGO – Progression-free survival for patients with rituximab-refractory indolent non-Hodgkin’s lymphomas was effectively doubled with a combination of obinutuzumab and bendamustine, compared with bendamustine alone.

Dr. Laura Helen Sehn from the British Columbia (Canada) Cancer Agency in Vancouver, says that the study, the GADOLIN trial. “is remarkable, because it does demonstrate the first randomized evidence of a clinical benefit of a novel anti-CD20 monoclonal antibiody for patients who are rituximab refractory.”

She described the study’s key findings at the annual meeting of the American Society of Clinical Oncology.

Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.

The results were published online April 20 in the Journal of Clinical Oncology.

The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).

Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.

At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.

Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).

“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.

“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.

Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.

Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.

Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.

The results were published online April 20 in the Journal of Clinical Oncology.

The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).

Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.

At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.

Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).

“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.

“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.

Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.

Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.

Failure-free survival and overall survival were similar between two combined modality therapies in patients with stage I or II bulky mediastinal Hodgkin’s lymphoma, investigators reported.

The results were published online April 20 in the Journal of Clinical Oncology.

The phase III trial evaluated outcomes following treatment with either doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or mechlorethamine, doxorubicin, vincristine, bleomycin, vinblastine, etoposide, and prednisone (Stanford V).

Median failure-free survival (FFS) and overall survival (OS) were not reached in either arm. The 5-year FFS and OS were 85% and 96% for ABVD, respectively, and 79% and 92% for Stanford V, reported Dr. Ranjana H. Advani, professor of oncology at Stanford (Calif.) University, and associates.

At a median follow up of 6.54 years, 19 treatment failures occurred in the ABVD arm and 23 in the Stanford V arm. In total, 14 deaths occurred, 5 in the ABVD group and 9 in the Stanford V group.

Approximately 20%-25% of patients with stage I or II Hodgkin’s lymphoma (HL) have bulky mediastinal involvement, and this was the first contemporary prospective trial to evaluate this patient subgroup, the investigators wrote (J. Clin. Oncol. 2015 April 20 [doi:10.1200/JCO.2014.57.8138]).

“This is important because ongoing trials in North America use mediastinal bulk as an eligibility criterion, and contemporary guidelines use it to define treatment algorithms,” Dr. Advani and associates said, noting that both regimens are acceptable treatment options.

“In addition, these results provide an important contemporary benchmark for comparison of ongoing and future studies,” they wrote.

Out of 854 patients with HL enrolled in the trial, 264 with bulky disease were eligible for the subgroup analysis; 135 received ABVD and 129 received Stanford V. After completion of chemotherapy, all patients received 36 Gy of modified involved field radiotherapy (IFRT). Patterns of relapse were similar between treatment arms, and less than 10% of patients had in-field recurrences, a finding that indicated effective local control with IFRT.

Both treatment arms had similar rates of grade 3-4 neutropenia, and the Stanford V arm had more grade 3 lymphopenia (83% vs. 46%, P < .001) and grade 3 and 4 sensory neuropathy. At 5 years, both groups had similar risks of second cancers: two in the ABVD group and six in the Stanford group. The assessment of risks associated with higher doses of anthracycline and bleomycin in ABVD and larger radiation fields in Stanford V requires longer follow-up, the researchers wrote.

Ibrutinib proved to be “highly active” against refractory Waldenstrom’s macroglobulinemia in the first clinical trial to assess the agent’s safety and efficacy in this patient population, producing an overall response rate of 90.5% and a major response rate of 73.0% in a series of 63 consecutive patients, according to a report published online April 9 in the New England Journal of Medicine.

Waldenstrom’s macroglobulinemia is a malignant B-cell lymphoma in which whole-genome sequencing has revealed several activating mutations. Ibrutinib – an oral inhibitor of Bruton’s tyrosine kinase (BTK), which is activated in tumor cells by some of these mutations – was found to trigger apoptosis of Waldenstrom’s macroglobulinemia cells in vitro and to show clinical activity in a phase I study. Investigators now report their findings from a prospective, industry-sponsored study of adults enrolled at the Dana-Farber Cancer Institute, Memorial Sloan-Kettering Cancer Center, and Stanford University Medical Center during a 1-year period and followed up for another 18 months.

All the participants had progressive disease at baseline despite receiving previous treatments including monoclonal antibodies, glucocorticoids, proteasome inhibitors, alkylators, immunomodulators, anthracyclines, and experimental therapies. Ibrutinib was taken orally every day for 26 4-week cycles until disease progressed or unacceptable toxic effects developed; treatment responders were permitted to continue the therapy after that time, if they wished, said Dr. Steven P. Treon of the Bing Center for Waldenstrom’s Macroglobulinemia, Dana-Farber Cancer Institute, Boston, and his associates.

The primary objective of the study was to determine the overall rate of any treatment response (it was 90.5%) and the rate of major treatment response, defined as a 50% or greater decline in serum IgM levels (it was 73.0%). In addition, at 24 months, the progression-free survival was 69.1% and the overall survival was 95.2%. In comparison, previous studies of other monotherapies have shown overall response rates of only 40%-80% and median progression-free survival of only 8-20 months, the investigators said (N. Engl. J. Med. 2015 April 9 [doi:10.1056/NEJMoa1501548]).

Treatment response was rapid, with a median onset at 4 weeks, and both serum IgM and hemoglobin levels improved even in patients who showed modest or no changes in bone marrow disease burden. “This suggests that a mechanism other than tumor debulking could contribute to the clinical benefit with ibrutinib,” they added.

On CT imaging, 68% of patients showed decreased or resolved adenopathy and 57% showed decreased splenomegaly. Malignant pleural effusions resolved in two of three patients who had them, and peripheral neuropathy stabilized or improved in all nine who were affected. The latter result is “particularly encouraging given the challenging nature of treating IgM-related peripheral neuropathy in Waldenstrom’s macroglobulinemia,” Dr. Treon and his associates noted.

The toxic effects of treatment were moderate in these heavily pretreated patients and included neutropenia (22% of patients), thrombocytopenia (14%), bleeding events (3%), and reversible atrial fibrillation (5%) in patients with a history of arrhythmia. There were few infections, and no unexpected toxicities occurred, the investigators reported.

This study was supported by Pharmacyclics and Janssen Pharmaceuticals; with additional funding by Peter S. Bing, M.D.; the International Waldenstrom’s Macroglobulinemia Foundation; the Leukemia and Lymphoma Society; the Linda and Edward Nelson Fund for Waldenstrom’s Macroglobulinemia Research; the D’Amato Family Fund for Genomic Discovery; the Coyote Fund; and the Bauman Family Foundation. Dr. Treon reported ties to Pharmacyclics and Janssen; his associates reported ties to several industry sources.

Ibrutinib proved to be “highly active” against refractory Waldenstrom’s macroglobulinemia in the first clinical trial to assess the agent’s safety and efficacy in this patient population, producing an overall response rate of 90.5% and a major response rate of 73.0% in a series of 63 consecutive patients, according to a report published online April 9 in the New England Journal of Medicine.

Waldenstrom’s macroglobulinemia is a malignant B-cell lymphoma in which whole-genome sequencing has revealed several activating mutations. Ibrutinib – an oral inhibitor of Bruton’s tyrosine kinase (BTK), which is activated in tumor cells by some of these mutations – was found to trigger apoptosis of Waldenstrom’s macroglobulinemia cells in vitro and to show clinical activity in a phase I study. Investigators now report their findings from a prospective, industry-sponsored study of adults enrolled at the Dana-Farber Cancer Institute, Memorial Sloan-Kettering Cancer Center, and Stanford University Medical Center during a 1-year period and followed up for another 18 months.

All the participants had progressive disease at baseline despite receiving previous treatments including monoclonal antibodies, glucocorticoids, proteasome inhibitors, alkylators, immunomodulators, anthracyclines, and experimental therapies. Ibrutinib was taken orally every day for 26 4-week cycles until disease progressed or unacceptable toxic effects developed; treatment responders were permitted to continue the therapy after that time, if they wished, said Dr. Steven P. Treon of the Bing Center for Waldenstrom’s Macroglobulinemia, Dana-Farber Cancer Institute, Boston, and his associates.

The primary objective of the study was to determine the overall rate of any treatment response (it was 90.5%) and the rate of major treatment response, defined as a 50% or greater decline in serum IgM levels (it was 73.0%). In addition, at 24 months, the progression-free survival was 69.1% and the overall survival was 95.2%. In comparison, previous studies of other monotherapies have shown overall response rates of only 40%-80% and median progression-free survival of only 8-20 months, the investigators said (N. Engl. J. Med. 2015 April 9 [doi:10.1056/NEJMoa1501548]).

Treatment response was rapid, with a median onset at 4 weeks, and both serum IgM and hemoglobin levels improved even in patients who showed modest or no changes in bone marrow disease burden. “This suggests that a mechanism other than tumor debulking could contribute to the clinical benefit with ibrutinib,” they added.

On CT imaging, 68% of patients showed decreased or resolved adenopathy and 57% showed decreased splenomegaly. Malignant pleural effusions resolved in two of three patients who had them, and peripheral neuropathy stabilized or improved in all nine who were affected. The latter result is “particularly encouraging given the challenging nature of treating IgM-related peripheral neuropathy in Waldenstrom’s macroglobulinemia,” Dr. Treon and his associates noted.

The toxic effects of treatment were moderate in these heavily pretreated patients and included neutropenia (22% of patients), thrombocytopenia (14%), bleeding events (3%), and reversible atrial fibrillation (5%) in patients with a history of arrhythmia. There were few infections, and no unexpected toxicities occurred, the investigators reported.

This study was supported by Pharmacyclics and Janssen Pharmaceuticals; with additional funding by Peter S. Bing, M.D.; the International Waldenstrom’s Macroglobulinemia Foundation; the Leukemia and Lymphoma Society; the Linda and Edward Nelson Fund for Waldenstrom’s Macroglobulinemia Research; the D’Amato Family Fund for Genomic Discovery; the Coyote Fund; and the Bauman Family Foundation. Dr. Treon reported ties to Pharmacyclics and Janssen; his associates reported ties to several industry sources.

Ibrutinib proved to be “highly active” against refractory Waldenstrom’s macroglobulinemia in the first clinical trial to assess the agent’s safety and efficacy in this patient population, producing an overall response rate of 90.5% and a major response rate of 73.0% in a series of 63 consecutive patients, according to a report published online April 9 in the New England Journal of Medicine.

Waldenstrom’s macroglobulinemia is a malignant B-cell lymphoma in which whole-genome sequencing has revealed several activating mutations. Ibrutinib – an oral inhibitor of Bruton’s tyrosine kinase (BTK), which is activated in tumor cells by some of these mutations – was found to trigger apoptosis of Waldenstrom’s macroglobulinemia cells in vitro and to show clinical activity in a phase I study. Investigators now report their findings from a prospective, industry-sponsored study of adults enrolled at the Dana-Farber Cancer Institute, Memorial Sloan-Kettering Cancer Center, and Stanford University Medical Center during a 1-year period and followed up for another 18 months.

All the participants had progressive disease at baseline despite receiving previous treatments including monoclonal antibodies, glucocorticoids, proteasome inhibitors, alkylators, immunomodulators, anthracyclines, and experimental therapies. Ibrutinib was taken orally every day for 26 4-week cycles until disease progressed or unacceptable toxic effects developed; treatment responders were permitted to continue the therapy after that time, if they wished, said Dr. Steven P. Treon of the Bing Center for Waldenstrom’s Macroglobulinemia, Dana-Farber Cancer Institute, Boston, and his associates.

The primary objective of the study was to determine the overall rate of any treatment response (it was 90.5%) and the rate of major treatment response, defined as a 50% or greater decline in serum IgM levels (it was 73.0%). In addition, at 24 months, the progression-free survival was 69.1% and the overall survival was 95.2%. In comparison, previous studies of other monotherapies have shown overall response rates of only 40%-80% and median progression-free survival of only 8-20 months, the investigators said (N. Engl. J. Med. 2015 April 9 [doi:10.1056/NEJMoa1501548]).

Treatment response was rapid, with a median onset at 4 weeks, and both serum IgM and hemoglobin levels improved even in patients who showed modest or no changes in bone marrow disease burden. “This suggests that a mechanism other than tumor debulking could contribute to the clinical benefit with ibrutinib,” they added.

On CT imaging, 68% of patients showed decreased or resolved adenopathy and 57% showed decreased splenomegaly. Malignant pleural effusions resolved in two of three patients who had them, and peripheral neuropathy stabilized or improved in all nine who were affected. The latter result is “particularly encouraging given the challenging nature of treating IgM-related peripheral neuropathy in Waldenstrom’s macroglobulinemia,” Dr. Treon and his associates noted.

The toxic effects of treatment were moderate in these heavily pretreated patients and included neutropenia (22% of patients), thrombocytopenia (14%), bleeding events (3%), and reversible atrial fibrillation (5%) in patients with a history of arrhythmia. There were few infections, and no unexpected toxicities occurred, the investigators reported.

This study was supported by Pharmacyclics and Janssen Pharmaceuticals; with additional funding by Peter S. Bing, M.D.; the International Waldenstrom’s Macroglobulinemia Foundation; the Leukemia and Lymphoma Society; the Linda and Edward Nelson Fund for Waldenstrom’s Macroglobulinemia Research; the D’Amato Family Fund for Genomic Discovery; the Coyote Fund; and the Bauman Family Foundation. Dr. Treon reported ties to Pharmacyclics and Janssen; his associates reported ties to several industry sources.

Brentuximab vedotin (Adcetris) increased progression-free survival to 43 months when given to adults with hard-to-treat Hodgkin’s lymphoma immediately after stem cell transplant, compared to 24 months for placebo, according to research published online March 18 in The Lancet.

As part of the AETHERA phase III trial, 329 patients with Hodgkin’s lymphoma who were at high risk of relapse or progression after autologous stem cell transplant were given brentuximab vedotin infusions or placebo every 3 weeks for up to 16 cycles. After a 2-year follow-up, the cancer had not progressed in 65% of the patients in the treatment group, compared with 45% in the placebo group.

The most common side effects were peripheral neuropathy (67% vs. 13% placebo) and neutropenia (35% vs. 12% placebo), noted Dr. Craig Moskowitz of Memorial Sloan Kettering Cancer Center, New York, and his associates.

Read the full article here.

Brentuximab vedotin (Adcetris) increased progression-free survival to 43 months when given to adults with hard-to-treat Hodgkin’s lymphoma immediately after stem cell transplant, compared to 24 months for placebo, according to research published online March 18 in The Lancet.

As part of the AETHERA phase III trial, 329 patients with Hodgkin’s lymphoma who were at high risk of relapse or progression after autologous stem cell transplant were given brentuximab vedotin infusions or placebo every 3 weeks for up to 16 cycles. After a 2-year follow-up, the cancer had not progressed in 65% of the patients in the treatment group, compared with 45% in the placebo group.

The most common side effects were peripheral neuropathy (67% vs. 13% placebo) and neutropenia (35% vs. 12% placebo), noted Dr. Craig Moskowitz of Memorial Sloan Kettering Cancer Center, New York, and his associates.

Read the full article here.

Brentuximab vedotin (Adcetris) increased progression-free survival to 43 months when given to adults with hard-to-treat Hodgkin’s lymphoma immediately after stem cell transplant, compared to 24 months for placebo, according to research published online March 18 in The Lancet.

As part of the AETHERA phase III trial, 329 patients with Hodgkin’s lymphoma who were at high risk of relapse or progression after autologous stem cell transplant were given brentuximab vedotin infusions or placebo every 3 weeks for up to 16 cycles. After a 2-year follow-up, the cancer had not progressed in 65% of the patients in the treatment group, compared with 45% in the placebo group.

The most common side effects were peripheral neuropathy (67% vs. 13% placebo) and neutropenia (35% vs. 12% placebo), noted Dr. Craig Moskowitz of Memorial Sloan Kettering Cancer Center, New York, and his associates.

Read the full article here.