Aggressive Lymphomas

Photo by Rhoda Baer

The National Comprehensive Cancer Network® (NCCN) has announced the release of the newly completed NCCN Radiation Therapy Compendium™.

This resource includes information designed to support clinical decision-making regarding the use of radiation therapy in cancer patients.

The content is based on the NCCN Clinical Practice Guidelines in Oncology and includes information from the 41 guidelines that reference radiation therapy.

“By compiling every recommendation for radiation therapy in one place, we’ve made it significantly easier for specialists . . .  to stay up-to-date on the very latest recommendations, regardless of how many different cancer types they treat,” said Robert W. Carlson, MD, chief executive officer of NCCN.

“This targeted content provides radiation oncologists with the specific, cutting-edge information they need, without forcing them to sift through any extraneous information. It’s part of our ongoing effort to always provide the most pertinent data on emerging treatment practices in the clearest, most efficient way possible.”

The NCCN Radiation Therapy Compendium includes a full complement of radiation therapy recommendations found in the current NCCN guidelines, including specific treatment modalities such as 2D/3D conformal external beam radiation therapy, intensity modulated radiation therapy, intra-operative radiation therapy, stereotactic radiosurgery/stereotactic body radiotherapy/stereotactic ablative body radiotherapy, image-guided radiation therapy, low dose-rate/high dose-rate brachytherapy, radioisotope, and particle therapy.

NCCN first announced the launch of the Radiation Therapy Compendium in March at the NCCN Annual Conference: Improving the Quality, Effectiveness, and Efficiency of Cancer Care.

At the time, the NCCN released a preliminary version of the compendium featuring 24 cancer types. The newly completed version now contains all 41 disease sites that are currently being treated using radiation therapy.

The compendium will be updated on a continual basis in conjunction with the library of clinical guidelines.

For more information and to access the NCCN Radiation Therapy Compendium, visit NCCN.org/RTCompendium. The compendium is available free-of-charge through March 2018.

Photo by Rhoda Baer

The National Comprehensive Cancer Network® (NCCN) has announced the release of the newly completed NCCN Radiation Therapy Compendium™.

This resource includes information designed to support clinical decision-making regarding the use of radiation therapy in cancer patients.

The content is based on the NCCN Clinical Practice Guidelines in Oncology and includes information from the 41 guidelines that reference radiation therapy.

“By compiling every recommendation for radiation therapy in one place, we’ve made it significantly easier for specialists . . .  to stay up-to-date on the very latest recommendations, regardless of how many different cancer types they treat,” said Robert W. Carlson, MD, chief executive officer of NCCN.

“This targeted content provides radiation oncologists with the specific, cutting-edge information they need, without forcing them to sift through any extraneous information. It’s part of our ongoing effort to always provide the most pertinent data on emerging treatment practices in the clearest, most efficient way possible.”

The NCCN Radiation Therapy Compendium includes a full complement of radiation therapy recommendations found in the current NCCN guidelines, including specific treatment modalities such as 2D/3D conformal external beam radiation therapy, intensity modulated radiation therapy, intra-operative radiation therapy, stereotactic radiosurgery/stereotactic body radiotherapy/stereotactic ablative body radiotherapy, image-guided radiation therapy, low dose-rate/high dose-rate brachytherapy, radioisotope, and particle therapy.

NCCN first announced the launch of the Radiation Therapy Compendium in March at the NCCN Annual Conference: Improving the Quality, Effectiveness, and Efficiency of Cancer Care.

At the time, the NCCN released a preliminary version of the compendium featuring 24 cancer types. The newly completed version now contains all 41 disease sites that are currently being treated using radiation therapy.

The compendium will be updated on a continual basis in conjunction with the library of clinical guidelines.

For more information and to access the NCCN Radiation Therapy Compendium, visit NCCN.org/RTCompendium. The compendium is available free-of-charge through March 2018.

Photo by Rhoda Baer

The National Comprehensive Cancer Network® (NCCN) has announced the release of the newly completed NCCN Radiation Therapy Compendium™.

This resource includes information designed to support clinical decision-making regarding the use of radiation therapy in cancer patients.

The content is based on the NCCN Clinical Practice Guidelines in Oncology and includes information from the 41 guidelines that reference radiation therapy.

“By compiling every recommendation for radiation therapy in one place, we’ve made it significantly easier for specialists . . .  to stay up-to-date on the very latest recommendations, regardless of how many different cancer types they treat,” said Robert W. Carlson, MD, chief executive officer of NCCN.

“This targeted content provides radiation oncologists with the specific, cutting-edge information they need, without forcing them to sift through any extraneous information. It’s part of our ongoing effort to always provide the most pertinent data on emerging treatment practices in the clearest, most efficient way possible.”

The NCCN Radiation Therapy Compendium includes a full complement of radiation therapy recommendations found in the current NCCN guidelines, including specific treatment modalities such as 2D/3D conformal external beam radiation therapy, intensity modulated radiation therapy, intra-operative radiation therapy, stereotactic radiosurgery/stereotactic body radiotherapy/stereotactic ablative body radiotherapy, image-guided radiation therapy, low dose-rate/high dose-rate brachytherapy, radioisotope, and particle therapy.

NCCN first announced the launch of the Radiation Therapy Compendium in March at the NCCN Annual Conference: Improving the Quality, Effectiveness, and Efficiency of Cancer Care.

At the time, the NCCN released a preliminary version of the compendium featuring 24 cancer types. The newly completed version now contains all 41 disease sites that are currently being treated using radiation therapy.

The compendium will be updated on a continual basis in conjunction with the library of clinical guidelines.

For more information and to access the NCCN Radiation Therapy Compendium, visit NCCN.org/RTCompendium. The compendium is available free-of-charge through March 2018.

Fred Hutch News Service

Researchers say they have identified potential biomarkers that may be used to help identify patients at an increased risk of neurotoxicity after chimeric antigen receptor (CAR) T-cell therapy.

The team also created an algorithm intended to identify patients whose symptoms were most likely to be life-threatening.

The researchers discovered the biomarkers and developed the algorithm based on data from a trial of JCAR014, an anti-CD19 CAR T-cell therapy, in patients with B-cell malignancies.

Cameron J. Turtle, MBBS, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues described this research in Cancer Discovery.

“It’s essential that we understand the potential side effects of CAR T therapies” Dr Turtle said. “While use of these cell therapies is likely to dramatically increase because they’ve been so effective in patients with resistant or refractory B-cell malignancies, there is still much to learn.”

Dr Turtle and his colleagues sought to provide a detailed clinical, radiological, and pathological characterization of neurotoxicity arising from anti-CD19 CAR T-cell therapy.

So the team analyzed data from a phase 1/2 trial of 133 adults with relapsed and/or refractory CD19+ B-cell acute lymphoblastic leukemia, non-Hodgkin lymphoma, or chronic lymphocytic leukemia.

The patients received lymphodepleting chemotherapy followed by an infusion of JCAR014.

Neurotoxicity

Within 28 days of treatment, 53 patients (40%) developed grade 1 or higher neurologic adverse events (AEs), 28 patients (21%) had grade 3 or higher neurotoxicity, and 4 patients (3%) developed fatal neurotoxicity.

Of the 53 patients with any neurologic AE, 48 (91%) also had cytokine release syndrome (CRS). All neurologic AEs in the 5 patients who did not have CRS were mild (grade 1) and transient.

Neurologic AEs included delirium with preserved alertness (66%), headache (55%), language disturbance (34%), decreased level of consciousness (25%), seizures (8%), and macroscopic intracranial hemorrhage (2%).

For most patients, neurotoxicity resolved by day 28 after CAR T-cell infusion. The exceptions were 1 patient in whom a grade 1 neurologic AE resolved 2 months after CAR T-cell infusion and the 4 patients who died of neurotoxicity.

The 4 neurotoxicity-related deaths were due to:

• Acute cerebral edema (n=2)
• Multifocal brainstem hemorrhage and edema associated with disseminated intravascular coagulation (n=1)
• Cortical laminar necrosis with a persistent minimally conscious state until death (n=1).

Potential biomarkers

In a univariate analysis, neurotoxicity was significantly more frequent in patients who:

• Had CRS (P<0.0001)
• Received a high CAR T-cell dose (P<0.0001)
• Had pre-existing neurologic comorbidities at baseline (P=0.0059).

In a multivariable analysis (which did not include CRS as a variable), patients had an increased risk of neurotoxicity if they:

• Had pre-existing neurologic comorbidities (P=0.0023)
• Received cyclophosphamide and fludarabine lymphodepletion (P=0.0259)
• Received a higher CAR T-cell dose (P=0.0009)
• Had a higher burden of malignant CD19+ B cells in the bone marrow (P=0.0165).

The researchers noted that patients who developed grade 3 or higher neurotoxicity had more severe CRS (P<0.0001).

“It appears that cytokine release syndrome is probably necessary for most cases of severe neurotoxicity, but, in terms of what triggers a person with cytokine release syndrome to get neurotoxicity, that’s something we need to investigate further,” said study author Kevin Hay, MD, of Fred Hutchinson Cancer Research Center.

Dr Hay and his colleagues also found that patients with severe neurotoxicity exhibited evidence of endothelial activation, which could contribute to manifestations such as capillary leak, disseminated intravascular coagulation, and disruption of the blood-brain barrier.

Algorithm

The researchers developed a predictive classification tree algorithm to identify patients who have an increased risk of severe neurotoxicity.

The algorithm suggests patients who meet the following criteria in the first 36 hours after CAR T-cell infusion have a high risk of grade 4-5 neurotoxicity:

• Fever of 38.9°C or greater
• Serum levels of IL6 at 16 pg/mL or higher
• Serum levels of MCP1 at 1343.5 pg/mL or higher.

This algorithm predicted severe neurotoxicity with 100% sensitivity and 94% specificity. Eight patients were misclassified, 1 of whom did not subsequently develop grade 2-3 neurotoxicity and/or grade 2 or higher CRS.

Funding

This research was funded by Juno Therapeutics Inc. (the company developing JCAR014), the National Cancer Institute, Life Science Discovery Fund, the Bezos family, the University of British Columbia Clinical Investigator Program, and via institutional funds from Bloodworks Northwest.

Dr Turtle receives research funding from Juno Therapeutics, holds patents licensed by Juno, and has pending patent applications that could be licensed by nonprofit institutions and for-profit companies, including Juno.

The Fred Hutchinson Cancer Research Center has a financial interest in Juno and receives licensing and other payments from the company.

Fred Hutch News Service

Researchers say they have identified potential biomarkers that may be used to help identify patients at an increased risk of neurotoxicity after chimeric antigen receptor (CAR) T-cell therapy.

The team also created an algorithm intended to identify patients whose symptoms were most likely to be life-threatening.

The researchers discovered the biomarkers and developed the algorithm based on data from a trial of JCAR014, an anti-CD19 CAR T-cell therapy, in patients with B-cell malignancies.

Cameron J. Turtle, MBBS, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues described this research in Cancer Discovery.

“It’s essential that we understand the potential side effects of CAR T therapies” Dr Turtle said. “While use of these cell therapies is likely to dramatically increase because they’ve been so effective in patients with resistant or refractory B-cell malignancies, there is still much to learn.”

Dr Turtle and his colleagues sought to provide a detailed clinical, radiological, and pathological characterization of neurotoxicity arising from anti-CD19 CAR T-cell therapy.

So the team analyzed data from a phase 1/2 trial of 133 adults with relapsed and/or refractory CD19+ B-cell acute lymphoblastic leukemia, non-Hodgkin lymphoma, or chronic lymphocytic leukemia.

The patients received lymphodepleting chemotherapy followed by an infusion of JCAR014.

Neurotoxicity

Within 28 days of treatment, 53 patients (40%) developed grade 1 or higher neurologic adverse events (AEs), 28 patients (21%) had grade 3 or higher neurotoxicity, and 4 patients (3%) developed fatal neurotoxicity.

Of the 53 patients with any neurologic AE, 48 (91%) also had cytokine release syndrome (CRS). All neurologic AEs in the 5 patients who did not have CRS were mild (grade 1) and transient.

Neurologic AEs included delirium with preserved alertness (66%), headache (55%), language disturbance (34%), decreased level of consciousness (25%), seizures (8%), and macroscopic intracranial hemorrhage (2%).

For most patients, neurotoxicity resolved by day 28 after CAR T-cell infusion. The exceptions were 1 patient in whom a grade 1 neurologic AE resolved 2 months after CAR T-cell infusion and the 4 patients who died of neurotoxicity.

The 4 neurotoxicity-related deaths were due to:

• Acute cerebral edema (n=2)
• Multifocal brainstem hemorrhage and edema associated with disseminated intravascular coagulation (n=1)
• Cortical laminar necrosis with a persistent minimally conscious state until death (n=1).

Potential biomarkers

In a univariate analysis, neurotoxicity was significantly more frequent in patients who:

• Had CRS (P<0.0001)
• Received a high CAR T-cell dose (P<0.0001)
• Had pre-existing neurologic comorbidities at baseline (P=0.0059).

In a multivariable analysis (which did not include CRS as a variable), patients had an increased risk of neurotoxicity if they:

• Had pre-existing neurologic comorbidities (P=0.0023)
• Received cyclophosphamide and fludarabine lymphodepletion (P=0.0259)
• Received a higher CAR T-cell dose (P=0.0009)
• Had a higher burden of malignant CD19+ B cells in the bone marrow (P=0.0165).

The researchers noted that patients who developed grade 3 or higher neurotoxicity had more severe CRS (P<0.0001).

“It appears that cytokine release syndrome is probably necessary for most cases of severe neurotoxicity, but, in terms of what triggers a person with cytokine release syndrome to get neurotoxicity, that’s something we need to investigate further,” said study author Kevin Hay, MD, of Fred Hutchinson Cancer Research Center.

Dr Hay and his colleagues also found that patients with severe neurotoxicity exhibited evidence of endothelial activation, which could contribute to manifestations such as capillary leak, disseminated intravascular coagulation, and disruption of the blood-brain barrier.

Algorithm

The researchers developed a predictive classification tree algorithm to identify patients who have an increased risk of severe neurotoxicity.

The algorithm suggests patients who meet the following criteria in the first 36 hours after CAR T-cell infusion have a high risk of grade 4-5 neurotoxicity:

• Fever of 38.9°C or greater
• Serum levels of IL6 at 16 pg/mL or higher
• Serum levels of MCP1 at 1343.5 pg/mL or higher.

This algorithm predicted severe neurotoxicity with 100% sensitivity and 94% specificity. Eight patients were misclassified, 1 of whom did not subsequently develop grade 2-3 neurotoxicity and/or grade 2 or higher CRS.

Funding

This research was funded by Juno Therapeutics Inc. (the company developing JCAR014), the National Cancer Institute, Life Science Discovery Fund, the Bezos family, the University of British Columbia Clinical Investigator Program, and via institutional funds from Bloodworks Northwest.

Dr Turtle receives research funding from Juno Therapeutics, holds patents licensed by Juno, and has pending patent applications that could be licensed by nonprofit institutions and for-profit companies, including Juno.

The Fred Hutchinson Cancer Research Center has a financial interest in Juno and receives licensing and other payments from the company.

Fred Hutch News Service

Researchers say they have identified potential biomarkers that may be used to help identify patients at an increased risk of neurotoxicity after chimeric antigen receptor (CAR) T-cell therapy.

The team also created an algorithm intended to identify patients whose symptoms were most likely to be life-threatening.

The researchers discovered the biomarkers and developed the algorithm based on data from a trial of JCAR014, an anti-CD19 CAR T-cell therapy, in patients with B-cell malignancies.

Cameron J. Turtle, MBBS, PhD, of Fred Hutchinson Cancer Research Center in Seattle, Washington, and his colleagues described this research in Cancer Discovery.

“It’s essential that we understand the potential side effects of CAR T therapies” Dr Turtle said. “While use of these cell therapies is likely to dramatically increase because they’ve been so effective in patients with resistant or refractory B-cell malignancies, there is still much to learn.”

Dr Turtle and his colleagues sought to provide a detailed clinical, radiological, and pathological characterization of neurotoxicity arising from anti-CD19 CAR T-cell therapy.

So the team analyzed data from a phase 1/2 trial of 133 adults with relapsed and/or refractory CD19+ B-cell acute lymphoblastic leukemia, non-Hodgkin lymphoma, or chronic lymphocytic leukemia.

The patients received lymphodepleting chemotherapy followed by an infusion of JCAR014.

Neurotoxicity

Within 28 days of treatment, 53 patients (40%) developed grade 1 or higher neurologic adverse events (AEs), 28 patients (21%) had grade 3 or higher neurotoxicity, and 4 patients (3%) developed fatal neurotoxicity.

Of the 53 patients with any neurologic AE, 48 (91%) also had cytokine release syndrome (CRS). All neurologic AEs in the 5 patients who did not have CRS were mild (grade 1) and transient.

Neurologic AEs included delirium with preserved alertness (66%), headache (55%), language disturbance (34%), decreased level of consciousness (25%), seizures (8%), and macroscopic intracranial hemorrhage (2%).

For most patients, neurotoxicity resolved by day 28 after CAR T-cell infusion. The exceptions were 1 patient in whom a grade 1 neurologic AE resolved 2 months after CAR T-cell infusion and the 4 patients who died of neurotoxicity.

The 4 neurotoxicity-related deaths were due to:

• Acute cerebral edema (n=2)
• Multifocal brainstem hemorrhage and edema associated with disseminated intravascular coagulation (n=1)
• Cortical laminar necrosis with a persistent minimally conscious state until death (n=1).

Potential biomarkers

In a univariate analysis, neurotoxicity was significantly more frequent in patients who:

• Had CRS (P<0.0001)
• Received a high CAR T-cell dose (P<0.0001)
• Had pre-existing neurologic comorbidities at baseline (P=0.0059).

In a multivariable analysis (which did not include CRS as a variable), patients had an increased risk of neurotoxicity if they:

• Had pre-existing neurologic comorbidities (P=0.0023)
• Received cyclophosphamide and fludarabine lymphodepletion (P=0.0259)
• Received a higher CAR T-cell dose (P=0.0009)
• Had a higher burden of malignant CD19+ B cells in the bone marrow (P=0.0165).

The researchers noted that patients who developed grade 3 or higher neurotoxicity had more severe CRS (P<0.0001).

“It appears that cytokine release syndrome is probably necessary for most cases of severe neurotoxicity, but, in terms of what triggers a person with cytokine release syndrome to get neurotoxicity, that’s something we need to investigate further,” said study author Kevin Hay, MD, of Fred Hutchinson Cancer Research Center.

Dr Hay and his colleagues also found that patients with severe neurotoxicity exhibited evidence of endothelial activation, which could contribute to manifestations such as capillary leak, disseminated intravascular coagulation, and disruption of the blood-brain barrier.

Algorithm

The researchers developed a predictive classification tree algorithm to identify patients who have an increased risk of severe neurotoxicity.

The algorithm suggests patients who meet the following criteria in the first 36 hours after CAR T-cell infusion have a high risk of grade 4-5 neurotoxicity:

• Fever of 38.9°C or greater
• Serum levels of IL6 at 16 pg/mL or higher
• Serum levels of MCP1 at 1343.5 pg/mL or higher.

This algorithm predicted severe neurotoxicity with 100% sensitivity and 94% specificity. Eight patients were misclassified, 1 of whom did not subsequently develop grade 2-3 neurotoxicity and/or grade 2 or higher CRS.

Funding

This research was funded by Juno Therapeutics Inc. (the company developing JCAR014), the National Cancer Institute, Life Science Discovery Fund, the Bezos family, the University of British Columbia Clinical Investigator Program, and via institutional funds from Bloodworks Northwest.

Dr Turtle receives research funding from Juno Therapeutics, holds patents licensed by Juno, and has pending patent applications that could be licensed by nonprofit institutions and for-profit companies, including Juno.

The Fred Hutchinson Cancer Research Center has a financial interest in Juno and receives licensing and other payments from the company.

Photo by Larry Young

Research published in Cell has revealed 150 genetic drivers of diffuse large B-cell lymphoma (DLBCL).

Among these drivers are 27 genes newly implicated in DLBCL, 35 functional oncogenes, and 9 genes that can be targeted with existing drugs.

Researchers used these findings to create a prognostic model that, they say, outperformed existing risk predictors in DLBCL.

“This work provides a comprehensive road map in terms of research and clinical priorities,” said study author Sandeep Dave, MD, of Duke University in Durham, North Carolina.

“We have very good data now to pursue new and existing therapies that might target the genetic mutations we identified. Additionally, this data could also be used to develop genetic markers that steer patients to therapies that would be most effective.”

Dr Dave and his colleagues began this research by analyzing tumor samples from 1001 patients who had been diagnosed with DLBCL over the past decade and were treated at 12 institutions around the world. There were 313 patients with ABC DLBCL, 331 with GCB DLBCL, and the rest were unclassified DLBCLs.

Using whole-exome sequencing, the researchers pinpointed 150 driver genes that were recurrently mutated in the DLBCL patients. This included 27 genes that, the researchers believe, had never before been implicated in DLBCL.

The team also found that ABC and GCB DLBCLs “shared the vast majority of driver genes at statistically indistinguishable frequencies.”

However, there were 20 genes that were differentially mutated between the 2 groups. For instance, EZH2, SGK1, GNA13, SOCS1, STAT6, and TNFRSF14 were more frequently mutated in GCB DLBCLs. And ETV6, MYD88, PIM1, and TBL1XR1 were more frequently mutated in ABC DLBCLs.

Essential genes

To identify genes essential to the development and maintenance of DLBCL, the researchers used CRISPR. The team knocked out genes in 6 cell lines—3 ABC DLBCLs (LY3, TMD8, and HBL1), 2 GCB DLBCLs (SUDHL4 and Pfeiffer), and 1 Burkitt lymphoma (BJAB) that phenotypically resembles GCB DLBCL.

This revealed 1956 essential genes. Knocking out these genes resulted in a significant decrease in cell fitness in at least 1 cell line.

The work also revealed 35 driver genes that, when knocked out, resulted in decreased viability of DLBCL cells, which classified them as functional oncogenes.

The researchers found that knockout of EBF1, IRF4, CARD11, MYD88, and IKBKB was selectively lethal in ABC DLBCL. And knockout of ZBTB7A, XPO1, TGFBR2, and PTPN6 was selectively lethal in GCB DLBCL.

In addition, the team noted that 9 of the driver genes are direct targets of drugs that are already approved or under investigation in clinical trials—MTOR, BCL2, SF3B1, SYK, PIM2, PIK3R1, XPO1, MCL1, and BTK.

Patient outcomes

The researchers also looked at the driver genes in the context of patient outcomes. The team found that mutations in MYC, CD79B, and ZFAT were strongly associated with poorer survival, while mutations in NF1 and SGK1 were associated with more favorable survival.

Mutations in KLHL14, BTG1, PAX5, and CDKN2A were associated with significantly poorer survival in ABC DLBCL, while mutations in CREBBP were associated with favorable survival in ABC DLBCL.

In GCB DLBCL, mutations in NFKBIA and NCOR1 were associated with poorer prognosis, while mutations in EZH2, MYD88, and ARID5B were associated with better prognosis.

Finally, the researchers developed a prognostic model based on combinations of genetic markers (the 150 driver genes) and gene expression markers (cell of origin, MYC, and BCL2).

The team found their prognostic model could predict survival more effectively than the International Prognostic Index, cell of origin alone, and MYC and BCL2 expression alone or together.

Photo by Larry Young

Research published in Cell has revealed 150 genetic drivers of diffuse large B-cell lymphoma (DLBCL).

Among these drivers are 27 genes newly implicated in DLBCL, 35 functional oncogenes, and 9 genes that can be targeted with existing drugs.

Researchers used these findings to create a prognostic model that, they say, outperformed existing risk predictors in DLBCL.

“This work provides a comprehensive road map in terms of research and clinical priorities,” said study author Sandeep Dave, MD, of Duke University in Durham, North Carolina.

“We have very good data now to pursue new and existing therapies that might target the genetic mutations we identified. Additionally, this data could also be used to develop genetic markers that steer patients to therapies that would be most effective.”

Dr Dave and his colleagues began this research by analyzing tumor samples from 1001 patients who had been diagnosed with DLBCL over the past decade and were treated at 12 institutions around the world. There were 313 patients with ABC DLBCL, 331 with GCB DLBCL, and the rest were unclassified DLBCLs.

Using whole-exome sequencing, the researchers pinpointed 150 driver genes that were recurrently mutated in the DLBCL patients. This included 27 genes that, the researchers believe, had never before been implicated in DLBCL.

The team also found that ABC and GCB DLBCLs “shared the vast majority of driver genes at statistically indistinguishable frequencies.”

However, there were 20 genes that were differentially mutated between the 2 groups. For instance, EZH2, SGK1, GNA13, SOCS1, STAT6, and TNFRSF14 were more frequently mutated in GCB DLBCLs. And ETV6, MYD88, PIM1, and TBL1XR1 were more frequently mutated in ABC DLBCLs.

Essential genes

To identify genes essential to the development and maintenance of DLBCL, the researchers used CRISPR. The team knocked out genes in 6 cell lines—3 ABC DLBCLs (LY3, TMD8, and HBL1), 2 GCB DLBCLs (SUDHL4 and Pfeiffer), and 1 Burkitt lymphoma (BJAB) that phenotypically resembles GCB DLBCL.

This revealed 1956 essential genes. Knocking out these genes resulted in a significant decrease in cell fitness in at least 1 cell line.

The work also revealed 35 driver genes that, when knocked out, resulted in decreased viability of DLBCL cells, which classified them as functional oncogenes.

The researchers found that knockout of EBF1, IRF4, CARD11, MYD88, and IKBKB was selectively lethal in ABC DLBCL. And knockout of ZBTB7A, XPO1, TGFBR2, and PTPN6 was selectively lethal in GCB DLBCL.

In addition, the team noted that 9 of the driver genes are direct targets of drugs that are already approved or under investigation in clinical trials—MTOR, BCL2, SF3B1, SYK, PIM2, PIK3R1, XPO1, MCL1, and BTK.

Patient outcomes

The researchers also looked at the driver genes in the context of patient outcomes. The team found that mutations in MYC, CD79B, and ZFAT were strongly associated with poorer survival, while mutations in NF1 and SGK1 were associated with more favorable survival.

Mutations in KLHL14, BTG1, PAX5, and CDKN2A were associated with significantly poorer survival in ABC DLBCL, while mutations in CREBBP were associated with favorable survival in ABC DLBCL.

In GCB DLBCL, mutations in NFKBIA and NCOR1 were associated with poorer prognosis, while mutations in EZH2, MYD88, and ARID5B were associated with better prognosis.

Finally, the researchers developed a prognostic model based on combinations of genetic markers (the 150 driver genes) and gene expression markers (cell of origin, MYC, and BCL2).

The team found their prognostic model could predict survival more effectively than the International Prognostic Index, cell of origin alone, and MYC and BCL2 expression alone or together.

Photo by Larry Young

Research published in Cell has revealed 150 genetic drivers of diffuse large B-cell lymphoma (DLBCL).

Among these drivers are 27 genes newly implicated in DLBCL, 35 functional oncogenes, and 9 genes that can be targeted with existing drugs.

Researchers used these findings to create a prognostic model that, they say, outperformed existing risk predictors in DLBCL.

“This work provides a comprehensive road map in terms of research and clinical priorities,” said study author Sandeep Dave, MD, of Duke University in Durham, North Carolina.

“We have very good data now to pursue new and existing therapies that might target the genetic mutations we identified. Additionally, this data could also be used to develop genetic markers that steer patients to therapies that would be most effective.”

Dr Dave and his colleagues began this research by analyzing tumor samples from 1001 patients who had been diagnosed with DLBCL over the past decade and were treated at 12 institutions around the world. There were 313 patients with ABC DLBCL, 331 with GCB DLBCL, and the rest were unclassified DLBCLs.

Using whole-exome sequencing, the researchers pinpointed 150 driver genes that were recurrently mutated in the DLBCL patients. This included 27 genes that, the researchers believe, had never before been implicated in DLBCL.

The team also found that ABC and GCB DLBCLs “shared the vast majority of driver genes at statistically indistinguishable frequencies.”

However, there were 20 genes that were differentially mutated between the 2 groups. For instance, EZH2, SGK1, GNA13, SOCS1, STAT6, and TNFRSF14 were more frequently mutated in GCB DLBCLs. And ETV6, MYD88, PIM1, and TBL1XR1 were more frequently mutated in ABC DLBCLs.

Essential genes

To identify genes essential to the development and maintenance of DLBCL, the researchers used CRISPR. The team knocked out genes in 6 cell lines—3 ABC DLBCLs (LY3, TMD8, and HBL1), 2 GCB DLBCLs (SUDHL4 and Pfeiffer), and 1 Burkitt lymphoma (BJAB) that phenotypically resembles GCB DLBCL.

This revealed 1956 essential genes. Knocking out these genes resulted in a significant decrease in cell fitness in at least 1 cell line.

The work also revealed 35 driver genes that, when knocked out, resulted in decreased viability of DLBCL cells, which classified them as functional oncogenes.

The researchers found that knockout of EBF1, IRF4, CARD11, MYD88, and IKBKB was selectively lethal in ABC DLBCL. And knockout of ZBTB7A, XPO1, TGFBR2, and PTPN6 was selectively lethal in GCB DLBCL.

In addition, the team noted that 9 of the driver genes are direct targets of drugs that are already approved or under investigation in clinical trials—MTOR, BCL2, SF3B1, SYK, PIM2, PIK3R1, XPO1, MCL1, and BTK.

Patient outcomes

The researchers also looked at the driver genes in the context of patient outcomes. The team found that mutations in MYC, CD79B, and ZFAT were strongly associated with poorer survival, while mutations in NF1 and SGK1 were associated with more favorable survival.

Mutations in KLHL14, BTG1, PAX5, and CDKN2A were associated with significantly poorer survival in ABC DLBCL, while mutations in CREBBP were associated with favorable survival in ABC DLBCL.

In GCB DLBCL, mutations in NFKBIA and NCOR1 were associated with poorer prognosis, while mutations in EZH2, MYD88, and ARID5B were associated with better prognosis.

Finally, the researchers developed a prognostic model based on combinations of genetic markers (the 150 driver genes) and gene expression markers (cell of origin, MYC, and BCL2).

The team found their prognostic model could predict survival more effectively than the International Prognostic Index, cell of origin alone, and MYC and BCL2 expression alone or together.

In a head-to-head trial of anti-CD20 monoclonal antibodies in first-line therapy for follicular lymphoma, obinutuzumab-based chemotherapy was associated with slightly but significantly better progression-free survival than rituximab-based therapy, but at the cost of higher toxicities, including severe adverse events.

Among 1,202 patients with follicular lymphoma followed for a median of 34.5 months, the estimated 3-year rate of progression-free survival (PFS) for patients randomized to obinutuzumab-based chemotherapy and maintenance was 80%, compared with 73.3% for patients randomized to rituximab chemotherapy and maintenance. Response rates and overall survival were similar between the treatment groups, Robert Marcus, MB, BS, of King’s College Hospital, London, and his coinvestigators reported in the GALLIUM trial.

In a head-to-head trial of anti-CD20 monoclonal antibodies in first-line therapy for follicular lymphoma, obinutuzumab-based chemotherapy was associated with slightly but significantly better progression-free survival than rituximab-based therapy, but at the cost of higher toxicities, including severe adverse events.

Among 1,202 patients with follicular lymphoma followed for a median of 34.5 months, the estimated 3-year rate of progression-free survival (PFS) for patients randomized to obinutuzumab-based chemotherapy and maintenance was 80%, compared with 73.3% for patients randomized to rituximab chemotherapy and maintenance. Response rates and overall survival were similar between the treatment groups, Robert Marcus, MB, BS, of King’s College Hospital, London, and his coinvestigators reported in the GALLIUM trial.

In a head-to-head trial of anti-CD20 monoclonal antibodies in first-line therapy for follicular lymphoma, obinutuzumab-based chemotherapy was associated with slightly but significantly better progression-free survival than rituximab-based therapy, but at the cost of higher toxicities, including severe adverse events.

Among 1,202 patients with follicular lymphoma followed for a median of 34.5 months, the estimated 3-year rate of progression-free survival (PFS) for patients randomized to obinutuzumab-based chemotherapy and maintenance was 80%, compared with 73.3% for patients randomized to rituximab chemotherapy and maintenance. Response rates and overall survival were similar between the treatment groups, Robert Marcus, MB, BS, of King’s College Hospital, London, and his coinvestigators reported in the GALLIUM trial.

Photo by Bill Branson

A study of cancer drugs approved by the European Commission from 2009 to 2013 showed that few hematology drugs were known to provide a benefit in overall survival (OS) or quality of life (QOL) over existing treatments.

Of 12 drugs approved for 17 hematology indications, 3 drugs had been shown to provide a benefit in OS (for 3 indications) at the time of approval.

None of the other hematology drugs were known to provide an OS benefit even after a median follow-up of 5.4 years.

Two hematology drugs were shown to provide a benefit in QOL (for 2 indications) after approval, but none of the drugs were known to provide a QOL benefit at the time of approval.

These findings were published in The BMJ alongside a related editorial, feature article, and patient commentary.

All cancer drugs

Researchers analyzed reports on all cancer drug approvals by the European Commission from 2009 to 2013.

There were 48 drugs approved for 68 cancer indications during this period. Fifty-one of the indications were for solid tumor malignancies, and 17 were for hematologic malignancies.

For 24 indications (35%), research had demonstrated a significant improvement in OS at the time of the drugs’ approval. For 3 indications, an improvement in OS was demonstrated after approval.

There was a known improvement in QOL for 7 of the indications (10%) at the time of approval and for 5 indications after approval.

The median follow-up was 5.4 years (range, 3.3 years to 8.1 years).

Overall, there was a significant improvement in OS or QOL during the study period for 51% of the indications (35/68). For the other half (49%, n=33), it wasn’t clear if the drugs provide any benefits in OS or QOL.

All cancer trials

The 68 approvals of cancer drugs were supported by 72 clinical trials.

Sixty approvals (88%) were supported by at least 1 randomized, controlled trial. Eight approvals (12%) were based on a single-arm study. This included 6 of 10 conditional marketing authorizations and 2 of 58 regular marketing authorizations.

Eighteen of the approvals (26%) were supported by a pivotal study powered to evaluate OS as the primary endpoint. And 37 of the approvals (54%) had a supporting pivotal trial evaluating QOL, but results were not reported for 2 of these trials.

Hematology trials and drugs

Of the 12 drugs approved for 17 hematology indications, 4 were regular approvals, 5 were conditional approvals, and 8 had orphan drug designation.

The approvals were supported by data from 18 trials—13 randomized and 5 single-arm trials.

The study drug was compared to an active comparator in 9 of the trials. The drug was evaluated as an add-on treatment in 4 trials. And the drug was not compared to anything in 5 trials (the single-arm trials).

OS was the primary endpoint in 1 of the trials, and 17 trials had OS or QOL as a secondary endpoint.

There were 3 drugs that had demonstrated an OS benefit at the time of approval but no QOL benefit at any time:

• Decitabine used for first-line treatment of acute myeloid leukemia in adults 65 and older who are ineligible for chemotherapy
• Pomalidomide in combination with dexamethasone as third-line therapy for relapsed/refractory multiple myeloma (MM)
• Rituximab plus chemotherapy for first-line treatment of chronic lymphocytic leukemia (CLL).

There were 2 drugs that had demonstrated a QOL benefit, only after approval, but they were not known to provide an OS benefit at any time:

• Nilotinib as a treatment for adults with newly diagnosed, chronic phase, Ph+ chronic myeloid leukemia (CML)
• Ofatumumab for CLL that is refractory to fludarabine and alemtuzumab

For the remaining drugs, there was no evidence of an OS or QOL benefit at any time during the period studied. The drugs included:

• Bortezomib given alone or in combination with doxorubicin or dexamethasone as second-line therapy for MM patients ineligible for hematopoietic stem cell transplant (HSCT)
• Bortezomib plus dexamethasone with or without thalidomide as first-line therapy in MM patients eligible for HSCT
• Bosutinib as second- or third-line treatment of Ph+ CML (any phase)
• Brentuximab vedotin for relapsed or refractory systemic anaplastic large-cell lymphoma
• Brentuximab vedotin for relapsed or refractory, CD30+ Hodgkin lymphoma after autologous HSCT or as third-line treatment for patients ineligible for autologous HSCT
• Dasatinib for first-line treatment of chronic phase, Ph+ CML
• Pixantrone for multiply relapsed or refractory B-cell non-Hodgkin lymphoma
• Ponatinib for patients with Ph+ acute lymphoblastic leukemia who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib or characterized by T315I mutation
• Ponatinib for patients with any phase of CML who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib/nilotinib or characterized by T315I mutation
• Rituximab as maintenance after induction for patients with follicular lymphoma
• Rituximab plus chemotherapy for relapsed or refractory CLL
• Temsirolimus for relapsed or refractory mantle cell lymphoma.
  

Photo by Bill Branson

A study of cancer drugs approved by the European Commission from 2009 to 2013 showed that few hematology drugs were known to provide a benefit in overall survival (OS) or quality of life (QOL) over existing treatments.

Of 12 drugs approved for 17 hematology indications, 3 drugs had been shown to provide a benefit in OS (for 3 indications) at the time of approval.

None of the other hematology drugs were known to provide an OS benefit even after a median follow-up of 5.4 years.

Two hematology drugs were shown to provide a benefit in QOL (for 2 indications) after approval, but none of the drugs were known to provide a QOL benefit at the time of approval.

These findings were published in The BMJ alongside a related editorial, feature article, and patient commentary.

All cancer drugs

Researchers analyzed reports on all cancer drug approvals by the European Commission from 2009 to 2013.

There were 48 drugs approved for 68 cancer indications during this period. Fifty-one of the indications were for solid tumor malignancies, and 17 were for hematologic malignancies.

For 24 indications (35%), research had demonstrated a significant improvement in OS at the time of the drugs’ approval. For 3 indications, an improvement in OS was demonstrated after approval.

There was a known improvement in QOL for 7 of the indications (10%) at the time of approval and for 5 indications after approval.

The median follow-up was 5.4 years (range, 3.3 years to 8.1 years).

Overall, there was a significant improvement in OS or QOL during the study period for 51% of the indications (35/68). For the other half (49%, n=33), it wasn’t clear if the drugs provide any benefits in OS or QOL.

All cancer trials

The 68 approvals of cancer drugs were supported by 72 clinical trials.

Sixty approvals (88%) were supported by at least 1 randomized, controlled trial. Eight approvals (12%) were based on a single-arm study. This included 6 of 10 conditional marketing authorizations and 2 of 58 regular marketing authorizations.

Eighteen of the approvals (26%) were supported by a pivotal study powered to evaluate OS as the primary endpoint. And 37 of the approvals (54%) had a supporting pivotal trial evaluating QOL, but results were not reported for 2 of these trials.

Hematology trials and drugs

Of the 12 drugs approved for 17 hematology indications, 4 were regular approvals, 5 were conditional approvals, and 8 had orphan drug designation.

The approvals were supported by data from 18 trials—13 randomized and 5 single-arm trials.

The study drug was compared to an active comparator in 9 of the trials. The drug was evaluated as an add-on treatment in 4 trials. And the drug was not compared to anything in 5 trials (the single-arm trials).

OS was the primary endpoint in 1 of the trials, and 17 trials had OS or QOL as a secondary endpoint.

There were 3 drugs that had demonstrated an OS benefit at the time of approval but no QOL benefit at any time:

• Decitabine used for first-line treatment of acute myeloid leukemia in adults 65 and older who are ineligible for chemotherapy
• Pomalidomide in combination with dexamethasone as third-line therapy for relapsed/refractory multiple myeloma (MM)
• Rituximab plus chemotherapy for first-line treatment of chronic lymphocytic leukemia (CLL).

There were 2 drugs that had demonstrated a QOL benefit, only after approval, but they were not known to provide an OS benefit at any time:

• Nilotinib as a treatment for adults with newly diagnosed, chronic phase, Ph+ chronic myeloid leukemia (CML)
• Ofatumumab for CLL that is refractory to fludarabine and alemtuzumab

For the remaining drugs, there was no evidence of an OS or QOL benefit at any time during the period studied. The drugs included:

• Bortezomib given alone or in combination with doxorubicin or dexamethasone as second-line therapy for MM patients ineligible for hematopoietic stem cell transplant (HSCT)
• Bortezomib plus dexamethasone with or without thalidomide as first-line therapy in MM patients eligible for HSCT
• Bosutinib as second- or third-line treatment of Ph+ CML (any phase)
• Brentuximab vedotin for relapsed or refractory systemic anaplastic large-cell lymphoma
• Brentuximab vedotin for relapsed or refractory, CD30+ Hodgkin lymphoma after autologous HSCT or as third-line treatment for patients ineligible for autologous HSCT
• Dasatinib for first-line treatment of chronic phase, Ph+ CML
• Pixantrone for multiply relapsed or refractory B-cell non-Hodgkin lymphoma
• Ponatinib for patients with Ph+ acute lymphoblastic leukemia who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib or characterized by T315I mutation
• Ponatinib for patients with any phase of CML who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib/nilotinib or characterized by T315I mutation
• Rituximab as maintenance after induction for patients with follicular lymphoma
• Rituximab plus chemotherapy for relapsed or refractory CLL
• Temsirolimus for relapsed or refractory mantle cell lymphoma.
  

Photo by Bill Branson

A study of cancer drugs approved by the European Commission from 2009 to 2013 showed that few hematology drugs were known to provide a benefit in overall survival (OS) or quality of life (QOL) over existing treatments.

Of 12 drugs approved for 17 hematology indications, 3 drugs had been shown to provide a benefit in OS (for 3 indications) at the time of approval.

None of the other hematology drugs were known to provide an OS benefit even after a median follow-up of 5.4 years.

Two hematology drugs were shown to provide a benefit in QOL (for 2 indications) after approval, but none of the drugs were known to provide a QOL benefit at the time of approval.

These findings were published in The BMJ alongside a related editorial, feature article, and patient commentary.

All cancer drugs

Researchers analyzed reports on all cancer drug approvals by the European Commission from 2009 to 2013.

There were 48 drugs approved for 68 cancer indications during this period. Fifty-one of the indications were for solid tumor malignancies, and 17 were for hematologic malignancies.

For 24 indications (35%), research had demonstrated a significant improvement in OS at the time of the drugs’ approval. For 3 indications, an improvement in OS was demonstrated after approval.

There was a known improvement in QOL for 7 of the indications (10%) at the time of approval and for 5 indications after approval.

The median follow-up was 5.4 years (range, 3.3 years to 8.1 years).

Overall, there was a significant improvement in OS or QOL during the study period for 51% of the indications (35/68). For the other half (49%, n=33), it wasn’t clear if the drugs provide any benefits in OS or QOL.

All cancer trials

The 68 approvals of cancer drugs were supported by 72 clinical trials.

Sixty approvals (88%) were supported by at least 1 randomized, controlled trial. Eight approvals (12%) were based on a single-arm study. This included 6 of 10 conditional marketing authorizations and 2 of 58 regular marketing authorizations.

Eighteen of the approvals (26%) were supported by a pivotal study powered to evaluate OS as the primary endpoint. And 37 of the approvals (54%) had a supporting pivotal trial evaluating QOL, but results were not reported for 2 of these trials.

Hematology trials and drugs

Of the 12 drugs approved for 17 hematology indications, 4 were regular approvals, 5 were conditional approvals, and 8 had orphan drug designation.

The approvals were supported by data from 18 trials—13 randomized and 5 single-arm trials.

The study drug was compared to an active comparator in 9 of the trials. The drug was evaluated as an add-on treatment in 4 trials. And the drug was not compared to anything in 5 trials (the single-arm trials).

OS was the primary endpoint in 1 of the trials, and 17 trials had OS or QOL as a secondary endpoint.

There were 3 drugs that had demonstrated an OS benefit at the time of approval but no QOL benefit at any time:

• Decitabine used for first-line treatment of acute myeloid leukemia in adults 65 and older who are ineligible for chemotherapy
• Pomalidomide in combination with dexamethasone as third-line therapy for relapsed/refractory multiple myeloma (MM)
• Rituximab plus chemotherapy for first-line treatment of chronic lymphocytic leukemia (CLL).

There were 2 drugs that had demonstrated a QOL benefit, only after approval, but they were not known to provide an OS benefit at any time:

• Nilotinib as a treatment for adults with newly diagnosed, chronic phase, Ph+ chronic myeloid leukemia (CML)
• Ofatumumab for CLL that is refractory to fludarabine and alemtuzumab

For the remaining drugs, there was no evidence of an OS or QOL benefit at any time during the period studied. The drugs included:

• Bortezomib given alone or in combination with doxorubicin or dexamethasone as second-line therapy for MM patients ineligible for hematopoietic stem cell transplant (HSCT)
• Bortezomib plus dexamethasone with or without thalidomide as first-line therapy in MM patients eligible for HSCT
• Bosutinib as second- or third-line treatment of Ph+ CML (any phase)
• Brentuximab vedotin for relapsed or refractory systemic anaplastic large-cell lymphoma
• Brentuximab vedotin for relapsed or refractory, CD30+ Hodgkin lymphoma after autologous HSCT or as third-line treatment for patients ineligible for autologous HSCT
• Dasatinib for first-line treatment of chronic phase, Ph+ CML
• Pixantrone for multiply relapsed or refractory B-cell non-Hodgkin lymphoma
• Ponatinib for patients with Ph+ acute lymphoblastic leukemia who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib or characterized by T315I mutation
• Ponatinib for patients with any phase of CML who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib/nilotinib or characterized by T315I mutation
• Rituximab as maintenance after induction for patients with follicular lymphoma
• Rituximab plus chemotherapy for relapsed or refractory CLL
• Temsirolimus for relapsed or refractory mantle cell lymphoma.
  

Research Hospital

New research suggests sperm banking may be underutilized by adolescent and young adult males with cancer who are at risk of infertility.

However, the study also showed that patients were more likely to attempt sperm banking if they were physically mature, met with fertility specialists, or their parents recommended sperm banking.

These findings were published in the Journal of Clinical Oncology.

“Research has found that the majority of males who survive childhood cancer desire biological children,” said study author James Klosky, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“Fertility preservation is also associated with a variety of benefits for survivors, including increased optimism about the future. While sperm banking is not for everyone, it is an effective method for preserving male fertility. Yet this study shows that sperm banking remains underutilized by at-risk patients with cancer.”

Dr Klosky and his colleagues surveyed 146 young males with cancer who were at risk of infertility. The researchers also surveyed 144 parents or guardians and 52 oncologists and other healthcare providers.

The patients’ mean age was 16.49 (range, 13.0-21.99). Diagnoses included leukemia and lymphoma (56.2%), solid tumor malignancies (37.7%), and brain tumors (6.2%).

Slightly more than half of the patients (53.4%, n=78) attempted sperm banking prior to starting treatment. Sixty-two, or 82.1%, of those who attempted sperm banking were successful.

In all, 43.8% of the patients successfully banked sperm.

Of the 68 patients who did not attempt sperm banking, 29 reported discussing the option with their families but deciding against it. Twenty-six patients indicated they did not believe sperm banking was necessary, and 9 patients were unsure what it was.

There were several factors that influenced the likelihood of patients making sperm collection attempts as well as successfully banking sperm.

In a multivariable analysis, the following factors were associated with an increased likelihood of attempting to bank sperm:

• Meeting with a fertility specialist (odds ratio[OR]=29.96; 95% CI, 2.48 to 361.41; P=0.007)
• Parent recommending banking (OR=12.30; 95% CI, 2.01 to 75.94; P=0.007)
• Higher Tanner stage (OR=5.42; 95% CI, 1.75 to 16.78; P=0.003).

In another multivariable analysis, successful sperm banking was associated with:

• Patient history of masturbation (OR=5.99; 95% CI, 1.25 to 28.50; P=0.025)
• Higher self-efficacy for banking coordination (OR=1.23; 95% CI, 1.05 to 1.45; P=0.012)
• Medical team member recommending banking (OR=4.26; 95% CI, 1.45 to 12.43; P=0.008)
• Parent recommending banking (OR=4.62; 95% CI, 1.46 to 14.73; P=0.010).

“These results highlight factors that providers can target to empower adolescents to actively participate in their own healthcare,” Dr Klosky said. “These decisions, which are typically made at the time of diagnosis, have high potential to affect their lives as survivors.”

Research Hospital

New research suggests sperm banking may be underutilized by adolescent and young adult males with cancer who are at risk of infertility.

However, the study also showed that patients were more likely to attempt sperm banking if they were physically mature, met with fertility specialists, or their parents recommended sperm banking.

These findings were published in the Journal of Clinical Oncology.

“Research has found that the majority of males who survive childhood cancer desire biological children,” said study author James Klosky, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“Fertility preservation is also associated with a variety of benefits for survivors, including increased optimism about the future. While sperm banking is not for everyone, it is an effective method for preserving male fertility. Yet this study shows that sperm banking remains underutilized by at-risk patients with cancer.”

Dr Klosky and his colleagues surveyed 146 young males with cancer who were at risk of infertility. The researchers also surveyed 144 parents or guardians and 52 oncologists and other healthcare providers.

The patients’ mean age was 16.49 (range, 13.0-21.99). Diagnoses included leukemia and lymphoma (56.2%), solid tumor malignancies (37.7%), and brain tumors (6.2%).

Slightly more than half of the patients (53.4%, n=78) attempted sperm banking prior to starting treatment. Sixty-two, or 82.1%, of those who attempted sperm banking were successful.

In all, 43.8% of the patients successfully banked sperm.

Of the 68 patients who did not attempt sperm banking, 29 reported discussing the option with their families but deciding against it. Twenty-six patients indicated they did not believe sperm banking was necessary, and 9 patients were unsure what it was.

There were several factors that influenced the likelihood of patients making sperm collection attempts as well as successfully banking sperm.

In a multivariable analysis, the following factors were associated with an increased likelihood of attempting to bank sperm:

• Meeting with a fertility specialist (odds ratio[OR]=29.96; 95% CI, 2.48 to 361.41; P=0.007)
• Parent recommending banking (OR=12.30; 95% CI, 2.01 to 75.94; P=0.007)
• Higher Tanner stage (OR=5.42; 95% CI, 1.75 to 16.78; P=0.003).

In another multivariable analysis, successful sperm banking was associated with:

• Patient history of masturbation (OR=5.99; 95% CI, 1.25 to 28.50; P=0.025)
• Higher self-efficacy for banking coordination (OR=1.23; 95% CI, 1.05 to 1.45; P=0.012)
• Medical team member recommending banking (OR=4.26; 95% CI, 1.45 to 12.43; P=0.008)
• Parent recommending banking (OR=4.62; 95% CI, 1.46 to 14.73; P=0.010).

“These results highlight factors that providers can target to empower adolescents to actively participate in their own healthcare,” Dr Klosky said. “These decisions, which are typically made at the time of diagnosis, have high potential to affect their lives as survivors.”

Research Hospital

New research suggests sperm banking may be underutilized by adolescent and young adult males with cancer who are at risk of infertility.

However, the study also showed that patients were more likely to attempt sperm banking if they were physically mature, met with fertility specialists, or their parents recommended sperm banking.

These findings were published in the Journal of Clinical Oncology.

“Research has found that the majority of males who survive childhood cancer desire biological children,” said study author James Klosky, PhD, of St. Jude Children’s Research Hospital in Memphis, Tennessee.

“Fertility preservation is also associated with a variety of benefits for survivors, including increased optimism about the future. While sperm banking is not for everyone, it is an effective method for preserving male fertility. Yet this study shows that sperm banking remains underutilized by at-risk patients with cancer.”

Dr Klosky and his colleagues surveyed 146 young males with cancer who were at risk of infertility. The researchers also surveyed 144 parents or guardians and 52 oncologists and other healthcare providers.

The patients’ mean age was 16.49 (range, 13.0-21.99). Diagnoses included leukemia and lymphoma (56.2%), solid tumor malignancies (37.7%), and brain tumors (6.2%).

Slightly more than half of the patients (53.4%, n=78) attempted sperm banking prior to starting treatment. Sixty-two, or 82.1%, of those who attempted sperm banking were successful.

In all, 43.8% of the patients successfully banked sperm.

Of the 68 patients who did not attempt sperm banking, 29 reported discussing the option with their families but deciding against it. Twenty-six patients indicated they did not believe sperm banking was necessary, and 9 patients were unsure what it was.

There were several factors that influenced the likelihood of patients making sperm collection attempts as well as successfully banking sperm.

In a multivariable analysis, the following factors were associated with an increased likelihood of attempting to bank sperm:

• Meeting with a fertility specialist (odds ratio[OR]=29.96; 95% CI, 2.48 to 361.41; P=0.007)
• Parent recommending banking (OR=12.30; 95% CI, 2.01 to 75.94; P=0.007)
• Higher Tanner stage (OR=5.42; 95% CI, 1.75 to 16.78; P=0.003).

In another multivariable analysis, successful sperm banking was associated with:

• Patient history of masturbation (OR=5.99; 95% CI, 1.25 to 28.50; P=0.025)
• Higher self-efficacy for banking coordination (OR=1.23; 95% CI, 1.05 to 1.45; P=0.012)
• Medical team member recommending banking (OR=4.26; 95% CI, 1.45 to 12.43; P=0.008)
• Parent recommending banking (OR=4.62; 95% CI, 1.46 to 14.73; P=0.010).

“These results highlight factors that providers can target to empower adolescents to actively participate in their own healthcare,” Dr Klosky said. “These decisions, which are typically made at the time of diagnosis, have high potential to affect their lives as survivors.”

Photo from Business Wire

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to brentuximab vedotin (BV, Adcetris) for use in combination with chemotherapy as frontline treatment of advanced classical Hodgkin lymphoma (HL).

Seattle Genetics and Takeda plan to submit a supplemental biologics license application seeking approval for BV in this indication before the end of this year.

The breakthrough designation is based on positive topline results from the phase 3 ECHELON-1 trial.

Full results from this trial are expected to be presented at the 2017 ASH Annual Meeting in December.

BV is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.

BV is currently FDA-approved to treat:

• Classical HL after failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates
• Classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation.

BV also has accelerated approval from the FDA for the treatment of systemic anaplastic large-cell lymphoma after failure of at least 1 prior multi-agent chemotherapy regimen. This approval is based on overall response rate. Continued approval of BV for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

ECHELON-1 trial

In this phase 3 trial, researchers compared BV in combination with doxorubicin, vinblastine, and dacarbazine to a recognized standard of care chemotherapy regimen in patients with previously untreated, advanced classical HL.

The study enrolled 1334 patients who had a histologically confirmed diagnosis of stage III or IV classical HL and had not been previously treated with systemic chemotherapy or radiotherapy.

The study’s primary endpoint is modified progression-free survival (PFS) per an independent review facility. Modified PFS is defined as the time to progression, death, or receipt of additional anticancer therapy for patients who are not in complete response after completion of frontline therapy.

There was a significant improvement in modified PFS in the BV arm compared to the control arm (hazard ratio=0.770; P=0.035). The 2-year modified PFS rate was 82.1% in the BV arm and 77.2% in the control arm.

An interim analysis of overall survival revealed a trend in favor of the BV arm.

The safety profile of BV plus chemotherapy was consistent with the profile known for the single-agent components of the regimen.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Photo from Business Wire

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to brentuximab vedotin (BV, Adcetris) for use in combination with chemotherapy as frontline treatment of advanced classical Hodgkin lymphoma (HL).

Seattle Genetics and Takeda plan to submit a supplemental biologics license application seeking approval for BV in this indication before the end of this year.

The breakthrough designation is based on positive topline results from the phase 3 ECHELON-1 trial.

Full results from this trial are expected to be presented at the 2017 ASH Annual Meeting in December.

BV is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.

BV is currently FDA-approved to treat:

• Classical HL after failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates
• Classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation.

BV also has accelerated approval from the FDA for the treatment of systemic anaplastic large-cell lymphoma after failure of at least 1 prior multi-agent chemotherapy regimen. This approval is based on overall response rate. Continued approval of BV for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

ECHELON-1 trial

In this phase 3 trial, researchers compared BV in combination with doxorubicin, vinblastine, and dacarbazine to a recognized standard of care chemotherapy regimen in patients with previously untreated, advanced classical HL.

The study enrolled 1334 patients who had a histologically confirmed diagnosis of stage III or IV classical HL and had not been previously treated with systemic chemotherapy or radiotherapy.

The study’s primary endpoint is modified progression-free survival (PFS) per an independent review facility. Modified PFS is defined as the time to progression, death, or receipt of additional anticancer therapy for patients who are not in complete response after completion of frontline therapy.

There was a significant improvement in modified PFS in the BV arm compared to the control arm (hazard ratio=0.770; P=0.035). The 2-year modified PFS rate was 82.1% in the BV arm and 77.2% in the control arm.

An interim analysis of overall survival revealed a trend in favor of the BV arm.

The safety profile of BV plus chemotherapy was consistent with the profile known for the single-agent components of the regimen.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Photo from Business Wire

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to brentuximab vedotin (BV, Adcetris) for use in combination with chemotherapy as frontline treatment of advanced classical Hodgkin lymphoma (HL).

Seattle Genetics and Takeda plan to submit a supplemental biologics license application seeking approval for BV in this indication before the end of this year.

The breakthrough designation is based on positive topline results from the phase 3 ECHELON-1 trial.

Full results from this trial are expected to be presented at the 2017 ASH Annual Meeting in December.

BV is an antibody-drug conjugate consisting of an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E.

BV is currently FDA-approved to treat:

• Classical HL after failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after failure of at least 2 prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates
• Classical HL patients at high risk of relapse or progression as post-auto-HSCT consolidation.

BV also has accelerated approval from the FDA for the treatment of systemic anaplastic large-cell lymphoma after failure of at least 1 prior multi-agent chemotherapy regimen. This approval is based on overall response rate. Continued approval of BV for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

ECHELON-1 trial

In this phase 3 trial, researchers compared BV in combination with doxorubicin, vinblastine, and dacarbazine to a recognized standard of care chemotherapy regimen in patients with previously untreated, advanced classical HL.

The study enrolled 1334 patients who had a histologically confirmed diagnosis of stage III or IV classical HL and had not been previously treated with systemic chemotherapy or radiotherapy.

The study’s primary endpoint is modified progression-free survival (PFS) per an independent review facility. Modified PFS is defined as the time to progression, death, or receipt of additional anticancer therapy for patients who are not in complete response after completion of frontline therapy.

There was a significant improvement in modified PFS in the BV arm compared to the control arm (hazard ratio=0.770; P=0.035). The 2-year modified PFS rate was 82.1% in the BV arm and 77.2% in the control arm.

An interim analysis of overall survival revealed a trend in favor of the BV arm.

The safety profile of BV plus chemotherapy was consistent with the profile known for the single-agent components of the regimen.

About breakthrough designation

The FDA’s breakthrough designation is intended to expedite the development and review of new treatments for serious or life-threatening conditions.

The designation entitles the company developing a therapy to more intensive FDA guidance on an efficient and accelerated development program, as well as eligibility for other actions to expedite FDA review, such as rolling submission and priority review.

To earn breakthrough designation, a treatment must show encouraging early clinical results demonstrating substantial improvement over available therapies with regard to a clinically significant endpoint, or it must fulfill an unmet need.

Photo courtesy of ASTRO

SAN DIEGO—New research suggests a need for mental health screening among cancer patients.

The study revealed a 40% rate of depression among patients treated at an urban cancer center over a 3-year period.

Three-quarters of the depressed patients were previously undiagnosed.

Female patients and those who were unable to work due to disability were more likely to be depressed.

Jason Domogauer, PhD, of Rutgers New Jersey Medical School in Newark, New Jersey, presented these findings at ASTRO’s 59th Annual Meeting.

“Depression is widely recognized as an underdiagnosed disorder, particularly among older adults and cancer patients,” Dr Domogauer said. “Our findings point to a clear need for action, including depression screening during initial and continuing patient visits, initiation of mental health treatments for identified patients, and increased collaboration with mental health providers in cancer treatment centers. These efforts are particularly important for patients in urban centers, those who are female, and those who are unable to work because of their disease.”

Dr Domogauer and his colleagues studied 400 cancer patients who received treatment at Rutgers New Jersey Medical School/University Hospital Cancer Center between 2013 and 2016.

The average patient age was 55 (range, 20-86), and 53% of patients were female. Forty-eight percent of patients were African-American, 29% were non-Hispanic white, and 16% were Hispanic.

Nearly equal numbers of patients reported being able to work (49%) or unable to work due to disability (51%). Most patients (85%) received radiation as part of their cancer treatment.

The researchers assessed depression in the patients using a minimum score of 16 on the Center for Epidemiologic Studies Depression Scale.

In this way, 40% of the patients were diagnosed with depression. In 75% of these patients, depression was previously undiagnosed. This means roughly 30% of the overall patient population suffered from undiagnosed and untreated depression.

Depression was more common among females than males—47% and 32%, respectively (odds ratio [OR]=1.9, P=0.007).

Depression was also more likely among patients who were unable to work due to disability—48%, compared to 33% of those able to work (OR=1.9, P=0.005).

Depression prevalence did not differ significantly among racial/ethnic groups.

When the researchers looked specifically at patients who were previously not diagnosed with depression, the effects of being female or unable to work persisted.

In this subgroup, depression was more common among women than men—43% and 29%, respectively (OR=1.9, P=0.02)—and patients with disability compared to able patients—43% and 31%, respectively (OR=1.7, P=0.03).

Photo courtesy of ASTRO

SAN DIEGO—New research suggests a need for mental health screening among cancer patients.

The study revealed a 40% rate of depression among patients treated at an urban cancer center over a 3-year period.

Three-quarters of the depressed patients were previously undiagnosed.

Female patients and those who were unable to work due to disability were more likely to be depressed.

Jason Domogauer, PhD, of Rutgers New Jersey Medical School in Newark, New Jersey, presented these findings at ASTRO’s 59th Annual Meeting.

“Depression is widely recognized as an underdiagnosed disorder, particularly among older adults and cancer patients,” Dr Domogauer said. “Our findings point to a clear need for action, including depression screening during initial and continuing patient visits, initiation of mental health treatments for identified patients, and increased collaboration with mental health providers in cancer treatment centers. These efforts are particularly important for patients in urban centers, those who are female, and those who are unable to work because of their disease.”

Dr Domogauer and his colleagues studied 400 cancer patients who received treatment at Rutgers New Jersey Medical School/University Hospital Cancer Center between 2013 and 2016.

The average patient age was 55 (range, 20-86), and 53% of patients were female. Forty-eight percent of patients were African-American, 29% were non-Hispanic white, and 16% were Hispanic.

Nearly equal numbers of patients reported being able to work (49%) or unable to work due to disability (51%). Most patients (85%) received radiation as part of their cancer treatment.

The researchers assessed depression in the patients using a minimum score of 16 on the Center for Epidemiologic Studies Depression Scale.

In this way, 40% of the patients were diagnosed with depression. In 75% of these patients, depression was previously undiagnosed. This means roughly 30% of the overall patient population suffered from undiagnosed and untreated depression.

Depression was more common among females than males—47% and 32%, respectively (odds ratio [OR]=1.9, P=0.007).

Depression was also more likely among patients who were unable to work due to disability—48%, compared to 33% of those able to work (OR=1.9, P=0.005).

Depression prevalence did not differ significantly among racial/ethnic groups.

When the researchers looked specifically at patients who were previously not diagnosed with depression, the effects of being female or unable to work persisted.

In this subgroup, depression was more common among women than men—43% and 29%, respectively (OR=1.9, P=0.02)—and patients with disability compared to able patients—43% and 31%, respectively (OR=1.7, P=0.03).

Photo courtesy of ASTRO

SAN DIEGO—New research suggests a need for mental health screening among cancer patients.

The study revealed a 40% rate of depression among patients treated at an urban cancer center over a 3-year period.

Three-quarters of the depressed patients were previously undiagnosed.

Female patients and those who were unable to work due to disability were more likely to be depressed.

Jason Domogauer, PhD, of Rutgers New Jersey Medical School in Newark, New Jersey, presented these findings at ASTRO’s 59th Annual Meeting.

“Depression is widely recognized as an underdiagnosed disorder, particularly among older adults and cancer patients,” Dr Domogauer said. “Our findings point to a clear need for action, including depression screening during initial and continuing patient visits, initiation of mental health treatments for identified patients, and increased collaboration with mental health providers in cancer treatment centers. These efforts are particularly important for patients in urban centers, those who are female, and those who are unable to work because of their disease.”

Dr Domogauer and his colleagues studied 400 cancer patients who received treatment at Rutgers New Jersey Medical School/University Hospital Cancer Center between 2013 and 2016.

The average patient age was 55 (range, 20-86), and 53% of patients were female. Forty-eight percent of patients were African-American, 29% were non-Hispanic white, and 16% were Hispanic.

Nearly equal numbers of patients reported being able to work (49%) or unable to work due to disability (51%). Most patients (85%) received radiation as part of their cancer treatment.

The researchers assessed depression in the patients using a minimum score of 16 on the Center for Epidemiologic Studies Depression Scale.

In this way, 40% of the patients were diagnosed with depression. In 75% of these patients, depression was previously undiagnosed. This means roughly 30% of the overall patient population suffered from undiagnosed and untreated depression.

Depression was more common among females than males—47% and 32%, respectively (odds ratio [OR]=1.9, P=0.007).

Depression was also more likely among patients who were unable to work due to disability—48%, compared to 33% of those able to work (OR=1.9, P=0.005).

Depression prevalence did not differ significantly among racial/ethnic groups.

When the researchers looked specifically at patients who were previously not diagnosed with depression, the effects of being female or unable to work persisted.

In this subgroup, depression was more common among women than men—43% and 29%, respectively (OR=1.9, P=0.02)—and patients with disability compared to able patients—43% and 31%, respectively (OR=1.7, P=0.03).

Adding bortezomib to the standard treatment regimen for diffuse large B-cell lymphoma (DLBCL) did not significantly impact outcomes, findings from the phase-2 PYRAMID trial showed.

When the proteasome inhibitor bortezomib was combined with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated non–germinal center B-cell–like (non-GCB) DLBCL, a significant improvement in progression-free survival (PFS) was not observed.

There also was no increase in 2-year PFS among patients treated with the combination of bortezomib plus R-CHOP (VR-CHOP), according to findings from the open-label, randomized study published in the Journal of Clinical Oncology (2017 Sep 1. doi: 10.1200/JCO.2017.73.2784).

Adding bortezomib to the standard treatment regimen for diffuse large B-cell lymphoma (DLBCL) did not significantly impact outcomes, findings from the phase-2 PYRAMID trial showed.

When the proteasome inhibitor bortezomib was combined with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated non–germinal center B-cell–like (non-GCB) DLBCL, a significant improvement in progression-free survival (PFS) was not observed.

There also was no increase in 2-year PFS among patients treated with the combination of bortezomib plus R-CHOP (VR-CHOP), according to findings from the open-label, randomized study published in the Journal of Clinical Oncology (2017 Sep 1. doi: 10.1200/JCO.2017.73.2784).

Adding bortezomib to the standard treatment regimen for diffuse large B-cell lymphoma (DLBCL) did not significantly impact outcomes, findings from the phase-2 PYRAMID trial showed.

When the proteasome inhibitor bortezomib was combined with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with previously untreated non–germinal center B-cell–like (non-GCB) DLBCL, a significant improvement in progression-free survival (PFS) was not observed.

There also was no increase in 2-year PFS among patients treated with the combination of bortezomib plus R-CHOP (VR-CHOP), according to findings from the open-label, randomized study published in the Journal of Clinical Oncology (2017 Sep 1. doi: 10.1200/JCO.2017.73.2784).

Mantle cell lymphoma

Results of a phase 3 trial suggest rituximab maintenance after transplant can prolong survival in non-elderly patients with mantle cell lymphoma (MCL).

Compared to patients who did not receive maintenance, those who received rituximab every other month for 3 years after autologous transplant had superior event-free survival (EFS), progression-free survival (PFS), and overall survival (OS).

Researchers reported these results in NEJM. The study was funded by Roche and Amgen.

“We demonstrate, with this study, that treatment with immunotherapy can delay the onset of relapse and prolong the survival of patients,” said study author Steven Le Gouill, MD, PhD, of CHU de Nantes in France.*

“It is clear that the use of rituximab maintenance after chemotherapy in this type of lymphoma will become a new standard of treatment.”

Dr Le Gouill and his colleagues began this study with 299 MCL patients. Their median age was 57 (range, 27-65), and 79% were male. Most had Ann Arbor stage IV disease (84%), followed by III (10%), and II (6%).

According to MIPI, 53% of patients had low-risk disease, 27% had intermediate-risk MCL, and 19% had high-risk disease. Ninety-four percent of patients had an ECOG performance status score below 3.

Treatment

Patients first received 4 courses of induction with R-DHAP (rituximab, dexamethasone, cytarabine, and a platinum derivative [carboplatin, oxaliplatin, or cisplatin]).

The overall response rate was 94%, with 41% (n=124) achieving a complete response (CR) and 36% (n=107) achieving an unconfirmed CR.

Twenty patients who had an insufficient response then received 4 courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Eleven of these patients went on to receive an autologous hematopoietic stem cell transplant (HSCT).

In all, 257 patients (86%) underwent autologous HSCT. The conditioning regimen was R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan).

Sixty-five percent of patients (n=168) achieved a CR after HSCT, and 24% (n=61) had an unconfirmed CR.

Up to 3 months after HSCT, patients were randomized to observation (n=120) or to receive rituximab (375 mg/m²) every 2 months for 3 years (n=120).

The researchers said there were no significant differences between these 2 groups regarding characteristics at study enrollment or the patients’ disease status at randomization.

Results

The median follow-up from randomization was 50.2 months (range, 46.4 to 54.2). The median EFS, PFS, and OS were not reached in either group.

The 4-year EFS was 79% in the rituximab group and 61% in the observation group (P=0.001). The 4-year PFS was 83% and 64%, respectively (P<0.001). And the 4-year OS was 89% and 80%, respectively (P=0.04).

Of the 11 patients who received R-CHOP before randomization, 4 were randomized to the rituximab group and 7 to the observation group.

One patient in the rituximab group relapsed and died. The other 3 were still alive and disease-free at the final analysis.

In the observation group, 4 patients had relapsed but were alive as of the final analysis, while 3 patients had died.

There were 59 patients who did not undergo randomization (due to disease progression, death, HSCT ineligibility, toxic effects, and other reasons).

For these patients, the median PFS was 11.0 months, and the median OS was 30.6 months.

*Quote has been translated from French.

Mantle cell lymphoma

Results of a phase 3 trial suggest rituximab maintenance after transplant can prolong survival in non-elderly patients with mantle cell lymphoma (MCL).

Compared to patients who did not receive maintenance, those who received rituximab every other month for 3 years after autologous transplant had superior event-free survival (EFS), progression-free survival (PFS), and overall survival (OS).

Researchers reported these results in NEJM. The study was funded by Roche and Amgen.

“We demonstrate, with this study, that treatment with immunotherapy can delay the onset of relapse and prolong the survival of patients,” said study author Steven Le Gouill, MD, PhD, of CHU de Nantes in France.*

“It is clear that the use of rituximab maintenance after chemotherapy in this type of lymphoma will become a new standard of treatment.”

Dr Le Gouill and his colleagues began this study with 299 MCL patients. Their median age was 57 (range, 27-65), and 79% were male. Most had Ann Arbor stage IV disease (84%), followed by III (10%), and II (6%).

According to MIPI, 53% of patients had low-risk disease, 27% had intermediate-risk MCL, and 19% had high-risk disease. Ninety-four percent of patients had an ECOG performance status score below 3.

Treatment

Patients first received 4 courses of induction with R-DHAP (rituximab, dexamethasone, cytarabine, and a platinum derivative [carboplatin, oxaliplatin, or cisplatin]).

The overall response rate was 94%, with 41% (n=124) achieving a complete response (CR) and 36% (n=107) achieving an unconfirmed CR.

Twenty patients who had an insufficient response then received 4 courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Eleven of these patients went on to receive an autologous hematopoietic stem cell transplant (HSCT).

In all, 257 patients (86%) underwent autologous HSCT. The conditioning regimen was R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan).

Sixty-five percent of patients (n=168) achieved a CR after HSCT, and 24% (n=61) had an unconfirmed CR.

Up to 3 months after HSCT, patients were randomized to observation (n=120) or to receive rituximab (375 mg/m²) every 2 months for 3 years (n=120).

The researchers said there were no significant differences between these 2 groups regarding characteristics at study enrollment or the patients’ disease status at randomization.

Results

The median follow-up from randomization was 50.2 months (range, 46.4 to 54.2). The median EFS, PFS, and OS were not reached in either group.

The 4-year EFS was 79% in the rituximab group and 61% in the observation group (P=0.001). The 4-year PFS was 83% and 64%, respectively (P<0.001). And the 4-year OS was 89% and 80%, respectively (P=0.04).

Of the 11 patients who received R-CHOP before randomization, 4 were randomized to the rituximab group and 7 to the observation group.

One patient in the rituximab group relapsed and died. The other 3 were still alive and disease-free at the final analysis.

In the observation group, 4 patients had relapsed but were alive as of the final analysis, while 3 patients had died.

There were 59 patients who did not undergo randomization (due to disease progression, death, HSCT ineligibility, toxic effects, and other reasons).

For these patients, the median PFS was 11.0 months, and the median OS was 30.6 months.

*Quote has been translated from French.

Mantle cell lymphoma

Results of a phase 3 trial suggest rituximab maintenance after transplant can prolong survival in non-elderly patients with mantle cell lymphoma (MCL).

Compared to patients who did not receive maintenance, those who received rituximab every other month for 3 years after autologous transplant had superior event-free survival (EFS), progression-free survival (PFS), and overall survival (OS).

Researchers reported these results in NEJM. The study was funded by Roche and Amgen.

“We demonstrate, with this study, that treatment with immunotherapy can delay the onset of relapse and prolong the survival of patients,” said study author Steven Le Gouill, MD, PhD, of CHU de Nantes in France.*

“It is clear that the use of rituximab maintenance after chemotherapy in this type of lymphoma will become a new standard of treatment.”

Dr Le Gouill and his colleagues began this study with 299 MCL patients. Their median age was 57 (range, 27-65), and 79% were male. Most had Ann Arbor stage IV disease (84%), followed by III (10%), and II (6%).

According to MIPI, 53% of patients had low-risk disease, 27% had intermediate-risk MCL, and 19% had high-risk disease. Ninety-four percent of patients had an ECOG performance status score below 3.

Treatment

Patients first received 4 courses of induction with R-DHAP (rituximab, dexamethasone, cytarabine, and a platinum derivative [carboplatin, oxaliplatin, or cisplatin]).

The overall response rate was 94%, with 41% (n=124) achieving a complete response (CR) and 36% (n=107) achieving an unconfirmed CR.

Twenty patients who had an insufficient response then received 4 courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Eleven of these patients went on to receive an autologous hematopoietic stem cell transplant (HSCT).

In all, 257 patients (86%) underwent autologous HSCT. The conditioning regimen was R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan).

Sixty-five percent of patients (n=168) achieved a CR after HSCT, and 24% (n=61) had an unconfirmed CR.

Up to 3 months after HSCT, patients were randomized to observation (n=120) or to receive rituximab (375 mg/m²) every 2 months for 3 years (n=120).

The researchers said there were no significant differences between these 2 groups regarding characteristics at study enrollment or the patients’ disease status at randomization.

Results

The median follow-up from randomization was 50.2 months (range, 46.4 to 54.2). The median EFS, PFS, and OS were not reached in either group.

The 4-year EFS was 79% in the rituximab group and 61% in the observation group (P=0.001). The 4-year PFS was 83% and 64%, respectively (P<0.001). And the 4-year OS was 89% and 80%, respectively (P=0.04).

Of the 11 patients who received R-CHOP before randomization, 4 were randomized to the rituximab group and 7 to the observation group.

One patient in the rituximab group relapsed and died. The other 3 were still alive and disease-free at the final analysis.

In the observation group, 4 patients had relapsed but were alive as of the final analysis, while 3 patients had died.

There were 59 patients who did not undergo randomization (due to disease progression, death, HSCT ineligibility, toxic effects, and other reasons).

For these patients, the median PFS was 11.0 months, and the median OS was 30.6 months.

*Quote has been translated from French.