FDA Approves Liso-Cel for Previously Treated Relapsed/Refractory Follicular Lymphoma

FDA Approves Liso-Cel for Previously Treated Relapsed/Refractory Follicular Lymphoma

The FDA has granted accelerated approval to lisocabtagene maraleucel (liso-cel; Breyanzi) for the treatment of adult patients with relapsed or refractory follicular lymphoma (FL) who previously received 2 or more lines of systemic therapy.¹

Liso-cel has also been included in the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology for B-Cell Lymphomas for third-line subsequent therapy for relapsed or refractory FL, particularly as a category 2A recommendation, according to a press release from Bristol Myers Squibb.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," M. Lia Palomba, MD, lymphoma and cell therapy specialist at Memorial Sloan Kettering Cancer Center in New York, said in the release from the pharmaceutical company. "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."

This approval was based on findings from the TRANSCEND-FL (NCT04245839) trial, according to a release from the FDA.¹ In this phase 2, open-label, multicenter, single-arm trial, researchers assessed the efficacy and safety of liso-cel in adult patients with relapsed or refractory FL after 2 or more lines of systemic therapy including an alkylating agent and an anti-CD20 antibody. Patients were able to enroll into this trial if they had an ECOG performance status of 1 or less and adequate bone marrow function to receive lymphodepleting chemotherapy.

After undergoing apheresis and before lymphodepletion and subsequent liso-cel, patients in the trial could receive bridging therapy for disease control, according to the release. In particular, patients in the trial received 1 dose of liso-cel 2 to 7 days after the completion of lymphodepleting chemotherapy, which consisted of fludarabine 30 mg/m2/day and cyclophosphamide 300 mg/m2/day simultaneously for 3 days.

The primary efficacy population of the TRANSCEND-FL trial included 94 patients with PET-positive disease either at the start of the trial or after bridging therapy, who received liso-cel in the intended dose range, and had at least 9 months of follow-up from the first response to therapy.

The main efficacy outcomes of the trial were overall response rate (ORR), defined as the percentage of patients with a best overall response of complete or partial response after liso-cel infusion, and duration of response (DOR), as assessed by an independent review committee.

Patients treated with liso-cel had an ORR of 95.7% (95% CI, 89.5%-98.8%) and a complete response rate of 73.4% (95% CI, 63.3%-82.0%.^1,2

The median time to response for patients treated with liso-cel was 2 month (range, 0.6-3.3).² The median DOR was not reached (NR; 95% CI, 18.04-NR) after a median follow-up of 16.8 months (95% CI, 16.3-17.0). Of the patients who responses to liso-cel, 80.9% remained in response at 12 months, and 77.1% remained in response at 18 months.

"Today's approval of Breyanzi for relapsed or refractory FL provides an option with potential for lasting remission in a 1-time infusion and a safety profile that allows for administration and monitoring in both the inpatient and outpatient setting in an increasing number of certified treatment centers in the US," Bryan Campbell, senior vice president and Head of Commercial of Cell Therapy at Bristol Myers Squibb, said in the company's release.²

The most common adverse reactions, occurring in at least 20% of patients in the trial, included headache, cytokine release syndrome, fatigue, musculoskeletal pain, fever, and constipation.¹ Of note, the FDA approved liso-cel with a Risk Evaluation and Mitigation Strategy due to the risk for fatal or life-threatening cytokine release syndrome and neurologic toxicities.

According to the FDA’s release, the recommended dose is 90 to 110 x 10⁶ CAR-positive viable T cells with a 1:1 ratio of CD4 and CD8 components.

"The lymphoma community has felt an urgent need for advancements in the treatment of relapsed or refractory follicular lymphoma," Meghan Gutierrez, chief executive officer of the Lymphoma Research Foundation, said in the release from Bristol Myers Squibb.² "The approval of Breyanzi offers patients a new and meaningful treatment option that provides hope for lasting remission."

References

1. FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. News release. FDA. May 15, 2024. Accessed May 15, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma
2. 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://www.businesswire.com/news/home/20240515772899/en/Bristol-Myers-Squibb%E2%80%99s-CAR-T-Cell-Therapy-Breyanzi-Approved-by-the-U.S.-Food-and-Drug-Administration-for-Relapsed-or-Refractory-Follicular-Lymphoma