Breyanzi delivers deep and durable responses in relapsed or refractory follicular lymphoma and mantle cell lymphoma in TRANSCEND clinical trials presented at ICML 2023

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 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.”