BMS's Liso-Cel Garners Positive CHMP Opinion for R/R Follicular Lymphoma

Bristol Myers Squibb (BMS)’s Type II variation application for lisocabtagene maraleucel (liso-cel, marketed as Breyanzi), an autologous CD19-directed CAR T-cell therapy, has received a recommendation for approval in relapsed/refractory (r/r) follicular lymphoma (FL) from the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP).¹

Specifically, the recommendation pertains to a potential indication for adults with r/r FL who have received 2 or more prior lines of systemic therapy. The opinion is based on data from the phase 2 TRANSCEND FL clinical trial (NCT04245839), which evaluated the therapy in patients with r/r indolent nonHodgkin lymphomas (NHL), including FL. Currently, liso-cel is indicated in the EU for the treatment of adults with r/r diffuse large B-cell lymphoma (DLBCL), high grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), and FL grade 3B (FL3B), who relapsed within 12 months from completion of, or are refractory to, first-line chemoimmunotherapy, and for adults with r/r DLBCL, PMBCL, and FL3B who have previously received at least 2 lines of systemic therapy.

“As a company at the forefront of advancing therapies that transform outcomes for some of the most difficult-to-treat cancers, CAR T-cell therapies are a significant focus of our research, and Breyanzi remains a cornerstone of our cell therapy portfolio and pipeline,” Anne Kerber, senior vice president, head of Late Clinical Development, Hematology, Oncology and Cell Therapy, at BMS, said in a statement.¹ “This is another important step in our commitment to delivering Breyanzi to more patients across indications, as well as expanding into new regions, especially for diseases with continued unmet need such as r/r FL, which is considered incurable.”

According to data presented at the 2023 American Society of Hematology (ASH) in December by Franck Morschhauser, MD, PhD, professor, hematology, University of Lille and Hospital Claude Huriez, and chair, Lymphoma Study Association, the efficacy evaluable patients in TRANSCEND FL with relapsed or refractory FL treated in the third-line plus setting (n = 101) had an overall response rate of 97% (95% CI, 91.6-99.4; one-sided P <.0001) and a complete response rate of 94% (95% CI, 87.5-97.8; one-sided P <.0001).² Furthermore, BMS stated that 75.7% (95% CI: 66.0–83.0) of patients were in response at 18 months posttreatment.

The Type II variation application for liso-cel was validated by the EMA August 2024.³ Notably, liso-cel had previously received accelerated approval from the FDA in May 2024 for treating adults with r/r follicular lymphoma who have received 2 or more prior lines of systemic therapy.⁴ Furthermore, the CAR-T was approved by the FDA for treating chronic lymphocytic leukemia or small lymphocytic lymphoma in March 2024.³ The therapy is also approved for the second-line treatment of r/r large B-cell lymphoma (LBCL) in the US, Japan, and Europe, and for relapsed and refractory LBCL after 2 or more lines of systemic therapy in Japan, Europe, Switzerland, and Canada.

CGTLive® recently spoke to Manali Kamdar, MD, the associate professor of medicine–hematology and clinical director of lymphoma services at the University of Colorado, about the curative potential of liso-cel in third-line r/r LBCL.⁴ Kamdar also discussed 5-year safety data from the TRANSCEND-NHL-001 clinical trial (NCT02631044) that evaluated the therapy in B-cell NHL, pointing out that there were no new toxicity signals since the 2-year follow-up.

“In the third line setting, we clearly have CAR T-cell therapy as a standard that a lot of physicians implement in the management of patients who have had 2 or more lines of treatment and have progressed with their diffuse LBCL,” Kamdar told CGTLive.

REFERENCES
1. Bristol Myers Squibb receives positive CHMP opinion for CAR T Cell Therapy Breyanzi for relapsed or refractory follicular lymphoma. News release. Bristol Myers Squibb. January 31, 2025. Accessed February 10, 2025. https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Receives-Positive-CHMP-Opinion-for-CAR-T-Cell-Therapy-Breyanzi-for-Relapsed-or-Refractory-Follicular-Lymphoma/default.aspx
2. Morschhauser F, Dahiya S, Palomba ML, et al. TRANSCEND FL: Phase 2 study primary analysis of lisocabtagenemaraleucel as second-line therapy in patients with high-risk relapsed or refractory follicular lymphoma. Presented at: 2023 ASH Annual Meeting & Exposition, December 9-12; San Diego, California. Abstract 602.
3. European Medicines Agency validates Bristol Myers Squibb’s application for CAR T cell therapy Breyanzi for relapsed or refractory follicular lymphoma. News release. Bristol Myers Squibb. August 19, 2024. Accessed February 10, 2025. https://news.bms.com/news/corporate-financial/2024/European-Medicines-Agency-Validates-Bristol-Myers-Squibbs-Application-for-CAR-T-Cell-Therapy-Breyanzi-for-Relapsed-or-Refractory-Follicular-Lymphoma/default.aspx
4. Abramson JS, Palomba ML, Gordon LI, et al. Five-year survival of patients (pts) from Transcend NHL 001 (TRANSCEND) supports curative potential of lisocabtagene maraleucel (liso-cel) in relapsed or refractory (r/r) large B-cell lymphoma (LBCL). Presented at: ASH 2024 Annual Meeting. December 7-10, 2024; San Diego, CA. Abstract 3125