FDA Grants Accelerated Approval for Liso-Cel for R/R Follicular Lymphoma

The FDA has granted Bristol Myers Squibb’s chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel; Breyanzi) accelerated approval for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who have received 2 or more prior lines of systemic therapy, the company announced on Wednesday.¹

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FL is a type of incurable of blood cancer that affects the lymph nodes, characterized by the abnormal growth of white blood cells within the lymph nodes, leading to the formation of follicle clumps. It is the second most common type of non-Hodgkin lymphoma and the most common type of slow-growing lymphoma.²

“In the treatment of relapsed or refractory follicular lymphoma, patients often cycle through treatments with typically shorter responses with each new line of therapy,” Maria L. Palomba, MD, TRANSCEND investigator and lymphoma and cell therapy specialist, Memorial Sloan Kettering Cancer Center, said in a statement.¹ “Those who have experienced early disease progression have notably poor prognosis. The FDA approval of liso-cel for patients with relapsed or refractory FL is an important advancement in addressing an ongoing unmet need in the FL treatment paradigm, providing patients a new option that has shown remarkably high response rates and an established safety profile.”

The FDA approval is based on results from the phase 2 TRANSCEND FL (NCT04245839) study, an open-label, global, multicenter, single-arm study with objective of determining the efficacy and safety of liso-cel in patients with relapsed or refractory indolent B-cell non-Hodgkin lymphoma. Results of the study were presented at the 2023 American Society of Hematology annual meeting.³

The primary outcome was the overall response rate (ORR), including best overall response of complete response or partial response as defined by an Independent Review Committee. Additionally, secondary outcome measures included complete response rate, duration of response, progression-free survival, and safety.

This study was the largest primary analysis set of patients with relapsed or refractory FL of a clinical trial evaluating CAR T-cell therapy in this patient population. In the study, the (ORR) was 95.7% (95% CI, 89.5-98.8) and the complete response (CR) rate was 73.4% (95% CI, 63.3-82.0).

Additionally, the median (IQR) time to response was 1 (0.6-3.3) month and median duration of response (DOR) not reached (95% CI, 18.04-not reached [NR]), with 80.9% of responders remaining in response at 12 months, and 77.1% of responders remaining in response at 18 months.

Furthermore, liso-cel had a consistent safety profile across clinical trials, with any grade cytokine release syndrome (CRS) occurred in 53% if patients, including Grade 3 or higher CRS in 4% of patients.

The most common adverse reactions in FL were CRS, in which Grade 3-4 laboratory abnormalities included lymphocyte count decreased, neutrophil count decreased, and white blood cell decrease.

Safety warnings for liso-cel include CRS, neurologic toxicities, T-cell malignancies, and availability only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Breyanzi REMS. 

Continued approval for liso-cel may be contingent on verification and description of clinical benefit in confirmatory trials.

“The lymphoma community has felt an urgent need for advancements in the treatment of relapsed or refractory follicular lymphoma,” said Meghan Gutierrez, chief executive officer, Lymphoma Research Foundation, in a statement.¹ “The approval of Breyanzi offers patients a new and meaningful treatment option that provides hope for lasting remission, and we are grateful to those who have contributed to this exciting milestone for patients.”

In March 2024, liso-cel was also granted accelerated approval for use in chronic lymphocytic leukemia and small lymphocytic leukemia, which is the first CAR T-cell therapy approved for the condition.⁴

References

1. Bristol Myers Squibb’s CAR T Cell Therapy Breyanzi Approved by the U.S. Food and Drug Administration for Relapsed or Refractory Follicular Lymphoma. News Release. Bristol Myers Squibb. May 15, 2024. Accessed May 16, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibbs-CAR-T-Cell-Therapy-Breyanzi-Approved-by-the-U.S.-Food-and-Drug-Administration-for-Relapsed-or-Refractory-Follicular-Lymphoma/default.aspx

2. What is follicular lymphoma? Follicular Lymphoma Foundation. Accessed May 16, 2024. https://www.theflf.org/what-is-fl/

3. Morschhauser F, Dahiya S, Palomba ML, et al. TRANSCEND FL: phase 2 study primary analysis of lisocabtagene maraleucel as second-line therapy in patients with high-risk relapsed or refractory follicular lymphoma. Presented: ASH 2023; December 9-12; San Diego, CA. Abstract 602.

4. Caffrey M. FDA grants accelerated approvel to liso-cel for CLL/SLL after BTK, BCL-2 inhibitors. The American Journal of Managed Care^®. March 14, 2024. Accessed May 16, 2024. https://www.ajmc.com/view/fda-grants-accelerated-approval-to-liso-cel-for-cll-sll-after-btk-bcl-2-inhibitors