BMS’s Application for Expanded Liso-Cel Indication in Follicular Lymphoma Validated by EMA

Bristol Myers Squibb (BMS)’s Type II variation application for lisocabtagene maraleucel (liso-cel, marketed as Breyanzi), an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy, in relapsed/refractory (r/r) follicular lymphoma (FL) has been validated by the European Medicines Agency (EMA).¹

Via the application, BMS is seeking to expand liso-cel's indication in the European Union to include adult patients with r/r FL who have previously received at least 2 prior lines of systemic therapy. 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.

“FL impacts a significant number of people, and those with r/r disease tend to experience shorter responses with each new line of therapy,” Anne Kerber, senior vice president, head of Late Clinical Development, Hematology, Oncology and Cell Therapy, at BMS, said in a statement.¹ “ Breyanzi represents a differentiated CAR T-cell therapy, and we look forward to working with the EMA to bring this important treatment option to patients with r/r FL with the goal of improving outcomes and providing lasting remission.”

Data from the phase 2 TRANSCEND FL clinical trial (NCT04245839), which included patients with r/r FL, supports the application. 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). The median duration of response was not reached at a median follow-up of 16.6 months and 81.9% of responders had an ongoing response at 12 months.²

“So far most of the responses are durable and we have a very good overall survival with only 1 patient dying. We need more follow up because the data are not mature bond one year and we should have that next year. But it’s really encouraging,” Morschhauser told CGTLive® at ASH.

In the United States, liso-cel was approved by the FDA for adults with r/r FL who have received 2 or more prior lines of systemic therapy on May 15, 2024.³ The approval was likewise supported by the data from TRANSCEND FL. Notably, even more recently, the FDA approved liso-cel for treating adults with r/r mantle cell lymphoma (MCL) who have been previously treated with at least 2 lines of systemic therapy, including a Bruton tyrosine kinase (BTK) inhibitor, on May 30, 2024.⁴

“It will be a very important part of our treatment paradigm,” Michael Wang, MD, a professor in the Department of Lymphoma/Myeloma at MD Anderson Cancer Center, who served as lead investigator on the phase 1 TRANSCEND NHL 001 clinical trial (NCT02631044) that led to liso-cel's approval in r/r MCL, told CGTLive in an interview following the FDA’s decision regarding that indication.

Breyanzi was also approved by the FDA for treating chronic lymphocytic leukemia or small lymphocytic lymphoma in March 2024.⁵ The therapy is also approved for the second-line treatment of r/r LBCL in the US and Japan and for r/r LBCL after 2 or more lines of systemic therapy in Japan, Switzerland, and Canada.

REFERENCES
1. 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 August 21, 2024. 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
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. FDA grants accelerated approval to lisocabtagenemaraleucel for follicular lymphoma. News release. FDA. May 15, 2024. Accessed August 21, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma
4. U.S. Food and Drug Administration Approves Bristol Myers Squibb’s Breyanzi as a New CAR T Cell Therapy for Relapsed or Refractory Mantle Cell Lymphoma. News release. FDA. May 30, 2024. Accessed August 21, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma
5. U.S. FDA Approves Bristol Myers Squibb’s Breyanzi ® as the First and Only CAR T Cell Therapy for Adults with Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL). News release. Bristol Myers Squibb. March 14, 2024. Accessed August 21, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-FDA-Approves-Bristol-Myers-Squibbs-Breyanzi--as-the-First-and-Only-CAR-T-Cell-Therapy-for-Adults-with-Relapsed-or-Refractory-Chronic-Lymphocytic-Leukemia-CLL-or-Small-Lymphocytic-Lymphoma-SLL/default.aspx