In TRANSCEND FL, 97% of patients with relapsed or refractory follicular lymphoma treated with Breyanzi achieved a response, with 94% achieving a complete response, and 81.9% of responders in ongoing response at 12 months
In TRANSCEND NHL 001, 86.5% of patients in the relapsed or refractory mantle cell lymphoma cohort achieved a response, with 74.3% achieving a complete response
Breyanzi showed a manageable safety profile, with no new safety signals and low rates of severe cytokine release syndrome and neurologic events in both studies
Results from TRANSCEND FL and TRANSCEND NHL 001 further underscore Breyanzi’s potential best-in-class and best-in-disease profile for a CD19-directed CAR T cell therapy in lymphomas
PRINCETON, NJ, USA I June 17, 2023 IBristol Myers Squibb (NYSE: BMY) announced the first disclosure of primary analysis results from two pivotal studies, TRANSCEND FL, an open-label, global, multicenter, Phase 2, single-arm study evaluating Breyanzi (lisocabtagene maraleucel; liso-cel) in patients with relapsed or refractory follicular lymphoma (FL) and the relapsed or refractory mantle cell lymphoma (MCL) cohort of TRANSCEND NHL 001, an open-label, multicenter, Phase 1, single-arm, seamless-design study evaluating Breyanzi. These data were presented in late-breaking oral presentations at the 2023 International Conference on Malignant Lymphoma (ICML) on Saturday, June 17.
“With Breyanzi, we’re dedicated to delivering a CAR T cell therapy with a differentiated profile to transform outcomes for some of the most difficult-to-treat lymphomas,” said Anne Kerber, senior vice president, head of Cell Therapy Development, Bristol Myers Squibb. “Based on results from TRANSCEND FL and TRANSCEND NHL 001, Breyanzi continues to demonstrate the ability to elicit significant deep and durable responses alongside a manageable safety profile, potentially addressing areas of high unmet need and reinforcing our commitment to advancing innovative solutions for the broadest array of hematologic malignancies of any CD19-directed CAR T cell therapy.”
Results from the TRANSCEND FL and TRANSCEND NHL 001 studies will be discussed with health authorities. Bristol Myers Squibb thanks the patients and investigators involved in the TRANSCEND clinical trials.
Results from TRANSCEND FL
TRANSCEND FL, the largest clinical trial to date to evaluate a CAR T cell therapy in patients with relapsed or refractory indolent non-Hodgkin lymphoma, including FL, enrolled adults with relapsed or refractory disease treated with Breyanzi in the second-line and third-line plus setting. Patients received treatment with Breyanzi at a target dose of 100 x 106 CAR-positive viable T cells.
In efficacy evaluable patients with relapsed or refractory FL treated with Breyanzi in the third-line plus setting (n=101), the overall response rate (ORR) was 97% (95% CI: 91.6-99.4; one-sided p<0.0001), with 94% of patients achieving a complete response (CR; 95% CI: 87.5-97.8; one-sided p<0.0001). Responses were durable with a median duration of response not reached at a median follow-up of 16.6 months. At 12 months, 81.9% of responders had an ongoing response. Median progression-free survival (PFS) was also not reached at a median follow-up of 17.5 months, with 12-month PFS achieved in 80.7% of patients.
With a median on-study follow-up of 18.9 months in the safety set (n=130), which included patients treated in the second-line plus setting, Breyanzi exhibited a manageable safety profile, with no new safety signals observed and low rates of severe cytokine release syndrome (CRS) and neurologic events (NE). Any grade CRS occurred in 58% of patients, with Grade 3 CRS occurring in 1% of patients and no Grade 4/5 CRS reported. Any grade NEs were reported in 15% of patients, with Grade 3 NEs occurring in 2% of patients and no Grade 4/5 NEs reported.
Historically, outcomes are poor for patients with relapsed or refractory FL. Despite high initial response rates to front-line treatment, the majority of patients experience multiple relapses and prognosis often worsens with subsequent relapses. Additionally, the durability of response with available treatment options decreases with each subsequent line of therapy. There are currently no curative options.
“In the treatment of relapsed or refractory follicular lymphoma, there are few options that offer significant and lasting responses, particularly for patients with high-risk disease features and those who experience early disease progression after front-line therapy,” said Franck Morschhauser, M.D., Ph.D., lead investigator and Professor of Hematology at Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les forms Injectables et les Technologies Associées, Lille, France. “In TRANSCEND FL, the overall and complete response rates achieved with liso-cel were very high, and appear mostly durable at 12 months, and, importantly, the safety profile was favorable. This data shows the potential of liso-cel as a promising treatment option for patients with relapsed or refractory follicular lymphoma.”
Results from TRANSCEND NHL 001 in MCL
The MCL cohort of TRANSCEND NHL 001 enrolled adults with relapsed or refractory disease after two or more prior lines of therapy, including a BTK inhibitor. These patients were treated with Breyanzi at dose levels of either 50 x 106 or 100 x 106 CAR-positive viable T cells.
With a median on-study follow-up of 16.1 months, the ORR in patients evaluated for efficacy in the primary analysis set (n=74) was 86.5% (95% CI: 76.5-93.3; one-sided p<0.0001), with 74.3% of patients achieving a CR (95% CI: 62.8-83.8; one-sided p<0.0001).
In the safety set (n=88), Breyanzi was well-tolerated and no new safety signals were observed. Any grade CRS occurred in 61% of patients, with Grade 3/4 CRS occurring in 1% of patients and no Grade 5 CRS reported. Any grade NEs were reported in 31% of patients, with Grade 3/4 NEs occurring in 9% of patients and no Grade 5 NEs reported.
There are currently no curative options for MCL and relapse is common, with many patients developing resistance to initial treatment. With each additional line of therapy, both response rates and duration of response tend to decrease, and prognosis worsens.
“Despite advances in treatment, there remains a critical unmet need for additional therapies that offer deep and durable responses in patients with high-risk, aggressive relapsed or refractory mantle cell lymphoma,” said Michael Wang, M.D., lead investigator and Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas. “Liso-cel offers the potential for complete responses with a one-time infusion and a manageable safety profile, representing a potential new treatment option for these patients.”
About TRANSCEND FL
TRANSCEND FL (NCT04245839) is an open-label, global, multicenter, Phase 2, single-arm study to determine the efficacy and safety of Breyanzi in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma, including follicular lymphoma and marginal zone lymphoma. The primary outcome measure is overall response rate. Secondary outcome measures include complete response rate, duration of response, and progression-free survival.
About TRANSCEND NHL 001
TRANSCEND NHL 001 (NCT02631044) is an open-label, multicenter, pivotal, Phase 1, single-arm, seamless-design study to determine the safety, pharmacokinetics and antitumor activity of Breyanzi in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B and mantle cell lymphoma. The primary outcome measures are treatment-related adverse events, dose-limiting toxicities and overall response rate. Secondary outcome measures include complete response rate, duration of response and progression-free survival.
About FL
Follicular lymphoma (FL) is the second most common, slow-growing form of non-Hodgkin lymphoma (NHL), accounting for 20 to 30 percent of all NHL cases. Most patients with FL are over 50 years of age when they are diagnosed. FL develops when white blood cells cluster together to form lumps in a person’s lymph nodes or organs. It is characterized by periods of remission and relapse, and the disease becomes more difficult to treat after relapse or disease progression.
About MCL
Mantle cell lymphoma (MCL) is an aggressive, rare form of non-Hodgkin lymphoma (NHL), representing roughly 3% of all NHL cases. MCL originates from cells in the “mantle zone” of the lymph node. MCL occurs more frequently in older adults with an average age at diagnosis in the mid-60s, and it is more often found in males than in females. In MCL, relapse after initial treatment is common, and for most, the disease eventually progresses or returns.
About Breyanzi
Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is made from a patient’s own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment. Breyanzi is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal LBCL, and follicular lymphoma grade 3B who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy, or refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant due to comorbidities or age, or relapsed or refractory disease after two or more lines of systemic therapy. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.
Please see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi regarding cytokine release syndrome and neurotoxicity.
Breyanzi is also approved in Japan and Europe for the second-line treatment of relapsed or refractory LBCL, and in Japan, Europe, Switzerland, and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy. Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in earlier lines of treatment for patients with relapsed or refractory LBCL and other types of lymphoma and leukemia. For more information, visit clinicaltrials.gov.
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision—transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
SOURCE: Bristol Myers Squibb
Post Views: 90
In TRANSCEND FL, 97% of patients with relapsed or refractory follicular lymphoma treated with Breyanzi achieved a response, with 94% achieving a complete response, and 81.9% of responders in ongoing response at 12 months
In TRANSCEND NHL 001, 86.5% of patients in the relapsed or refractory mantle cell lymphoma cohort achieved a response, with 74.3% achieving a complete response
Breyanzi showed a manageable safety profile, with no new safety signals and low rates of severe cytokine release syndrome and neurologic events in both studies
Results from TRANSCEND FL and TRANSCEND NHL 001 further underscore Breyanzi’s potential best-in-class and best-in-disease profile for a CD19-directed CAR T cell therapy in lymphomas
PRINCETON, NJ, USA I June 17, 2023 IBristol Myers Squibb (NYSE: BMY) announced the first disclosure of primary analysis results from two pivotal studies, TRANSCEND FL, an open-label, global, multicenter, Phase 2, single-arm study evaluating Breyanzi (lisocabtagene maraleucel; liso-cel) in patients with relapsed or refractory follicular lymphoma (FL) and the relapsed or refractory mantle cell lymphoma (MCL) cohort of TRANSCEND NHL 001, an open-label, multicenter, Phase 1, single-arm, seamless-design study evaluating Breyanzi. These data were presented in late-breaking oral presentations at the 2023 International Conference on Malignant Lymphoma (ICML) on Saturday, June 17.
“With Breyanzi, we’re dedicated to delivering a CAR T cell therapy with a differentiated profile to transform outcomes for some of the most difficult-to-treat lymphomas,” said Anne Kerber, senior vice president, head of Cell Therapy Development, Bristol Myers Squibb. “Based on results from TRANSCEND FL and TRANSCEND NHL 001, Breyanzi continues to demonstrate the ability to elicit significant deep and durable responses alongside a manageable safety profile, potentially addressing areas of high unmet need and reinforcing our commitment to advancing innovative solutions for the broadest array of hematologic malignancies of any CD19-directed CAR T cell therapy.”
Results from the TRANSCEND FL and TRANSCEND NHL 001 studies will be discussed with health authorities. Bristol Myers Squibb thanks the patients and investigators involved in the TRANSCEND clinical trials.
Results from TRANSCEND FL
TRANSCEND FL, the largest clinical trial to date to evaluate a CAR T cell therapy in patients with relapsed or refractory indolent non-Hodgkin lymphoma, including FL, enrolled adults with relapsed or refractory disease treated with Breyanzi in the second-line and third-line plus setting. Patients received treatment with Breyanzi at a target dose of 100 x 106 CAR-positive viable T cells.
In efficacy evaluable patients with relapsed or refractory FL treated with Breyanzi in the third-line plus setting (n=101), the overall response rate (ORR) was 97% (95% CI: 91.6-99.4; one-sided p<0.0001), with 94% of patients achieving a complete response (CR; 95% CI: 87.5-97.8; one-sided p<0.0001). Responses were durable with a median duration of response not reached at a median follow-up of 16.6 months. At 12 months, 81.9% of responders had an ongoing response. Median progression-free survival (PFS) was also not reached at a median follow-up of 17.5 months, with 12-month PFS achieved in 80.7% of patients.
With a median on-study follow-up of 18.9 months in the safety set (n=130), which included patients treated in the second-line plus setting, Breyanzi exhibited a manageable safety profile, with no new safety signals observed and low rates of severe cytokine release syndrome (CRS) and neurologic events (NE). Any grade CRS occurred in 58% of patients, with Grade 3 CRS occurring in 1% of patients and no Grade 4/5 CRS reported. Any grade NEs were reported in 15% of patients, with Grade 3 NEs occurring in 2% of patients and no Grade 4/5 NEs reported.
Historically, outcomes are poor for patients with relapsed or refractory FL. Despite high initial response rates to front-line treatment, the majority of patients experience multiple relapses and prognosis often worsens with subsequent relapses. Additionally, the durability of response with available treatment options decreases with each subsequent line of therapy. There are currently no curative options.
“In the treatment of relapsed or refractory follicular lymphoma, there are few options that offer significant and lasting responses, particularly for patients with high-risk disease features and those who experience early disease progression after front-line therapy,” said Franck Morschhauser, M.D., Ph.D., lead investigator and Professor of Hematology at Centre Hospitalier Universitaire de Lille, Groupe de Recherche sur les forms Injectables et les Technologies Associées, Lille, France. “In TRANSCEND FL, the overall and complete response rates achieved with liso-cel were very high, and appear mostly durable at 12 months, and, importantly, the safety profile was favorable. This data shows the potential of liso-cel as a promising treatment option for patients with relapsed or refractory follicular lymphoma.”
Results from TRANSCEND NHL 001 in MCL
The MCL cohort of TRANSCEND NHL 001 enrolled adults with relapsed or refractory disease after two or more prior lines of therapy, including a BTK inhibitor. These patients were treated with Breyanzi at dose levels of either 50 x 106 or 100 x 106 CAR-positive viable T cells.
With a median on-study follow-up of 16.1 months, the ORR in patients evaluated for efficacy in the primary analysis set (n=74) was 86.5% (95% CI: 76.5-93.3; one-sided p<0.0001), with 74.3% of patients achieving a CR (95% CI: 62.8-83.8; one-sided p<0.0001).
In the safety set (n=88), Breyanzi was well-tolerated and no new safety signals were observed. Any grade CRS occurred in 61% of patients, with Grade 3/4 CRS occurring in 1% of patients and no Grade 5 CRS reported. Any grade NEs were reported in 31% of patients, with Grade 3/4 NEs occurring in 9% of patients and no Grade 5 NEs reported.
There are currently no curative options for MCL and relapse is common, with many patients developing resistance to initial treatment. With each additional line of therapy, both response rates and duration of response tend to decrease, and prognosis worsens.
“Despite advances in treatment, there remains a critical unmet need for additional therapies that offer deep and durable responses in patients with high-risk, aggressive relapsed or refractory mantle cell lymphoma,” said Michael Wang, M.D., lead investigator and Professor, Department of Lymphoma and Myeloma, Division of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas. “Liso-cel offers the potential for complete responses with a one-time infusion and a manageable safety profile, representing a potential new treatment option for these patients.”
About TRANSCEND FL
TRANSCEND FL (NCT04245839) is an open-label, global, multicenter, Phase 2, single-arm study to determine the efficacy and safety of Breyanzi in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma, including follicular lymphoma and marginal zone lymphoma. The primary outcome measure is overall response rate. Secondary outcome measures include complete response rate, duration of response, and progression-free survival.
About TRANSCEND NHL 001
TRANSCEND NHL 001 (NCT02631044) is an open-label, multicenter, pivotal, Phase 1, single-arm, seamless-design study to determine the safety, pharmacokinetics and antitumor activity of Breyanzi in patients with relapsed or refractory B-cell non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, high-grade B-cell lymphoma, primary mediastinal B-cell lymphoma, follicular lymphoma Grade 3B and mantle cell lymphoma. The primary outcome measures are treatment-related adverse events, dose-limiting toxicities and overall response rate. Secondary outcome measures include complete response rate, duration of response and progression-free survival.
About FL
Follicular lymphoma (FL) is the second most common, slow-growing form of non-Hodgkin lymphoma (NHL), accounting for 20 to 30 percent of all NHL cases. Most patients with FL are over 50 years of age when they are diagnosed. FL develops when white blood cells cluster together to form lumps in a person’s lymph nodes or organs. It is characterized by periods of remission and relapse, and the disease becomes more difficult to treat after relapse or disease progression.
About MCL
Mantle cell lymphoma (MCL) is an aggressive, rare form of non-Hodgkin lymphoma (NHL), representing roughly 3% of all NHL cases. MCL originates from cells in the “mantle zone” of the lymph node. MCL occurs more frequently in older adults with an average age at diagnosis in the mid-60s, and it is more often found in males than in females. In MCL, relapse after initial treatment is common, and for most, the disease eventually progresses or returns.
About Breyanzi
Breyanzi is a CD19-directed CAR T cell therapy with a 4-1BB costimulatory domain, which enhances the expansion and persistence of the CAR T cells. Breyanzi is made from a patient’s own T cells, which are collected and genetically reengineered to become CAR T cells that are then delivered via infusion as a one-time treatment. Breyanzi is approved by the U.S. Food and Drug Administration (FDA) for the treatment of adult patients with large B-cell lymphoma (LBCL), including diffuse large B-cell lymphoma (DLBCL), not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal LBCL, and follicular lymphoma grade 3B who have refractory disease to first-line chemoimmunotherapy or relapse within 12 months of first-line chemoimmunotherapy, or refractory disease to first-line chemoimmunotherapy or relapse after first-line chemoimmunotherapy and are not eligible for hematopoietic stem cell transplant due to comorbidities or age, or relapsed or refractory disease after two or more lines of systemic therapy. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.
Please see the Important Safety Information section below, including Boxed WARNINGS for Breyanzi regarding cytokine release syndrome and neurotoxicity.
Breyanzi is also approved in Japan and Europe for the second-line treatment of relapsed or refractory LBCL, and in Japan, Europe, Switzerland, and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy. Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in earlier lines of treatment for patients with relapsed or refractory LBCL and other types of lymphoma and leukemia. For more information, visit clinicaltrials.gov.
Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.
Bristol Myers Squibb: Creating a Better Future for People with Cancer
Bristol Myers Squibb is inspired by a single vision—transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.
Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here.
About Bristol Myers Squibb
Bristol Myers Squibb is a global biopharmaceutical company whose mission is to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. For more information about Bristol Myers Squibb, visit us at BMS.com or follow us on LinkedIn, Twitter, YouTube, Facebook and Instagram.
SOURCE: Bristol Myers Squibb
Post Views: 90
