Liso-Cel Earns CHMP Recommendation for R/R Follicular Lymphoma

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has recommended the approval of lisocabtagene maraleucel (liso-cel; Breyanzi) for the treatment of adult patients with relapsed/refractory follicular lymphoma who have received 2 or more prior lines of systemic therapy.1

The recommendation was supported by data from the phase 2 TRANSCEND FL trial (NCT04245839), which showed that patients with relapsed/refractory follicular lymphoma experienced an overall response rate (ORR) of 97.1% (95% CI, 91.7%-99.4%), including a complete response (CR) rate of 94.2% (95% CI, 87.8%-97.8%). The 18-month duration of response (DOR) rate was 75.7% (95% CI, 66.0%-83.0%).

Safety data from the study were consistent with the known adverse effect profile of liso-cel, and no new safety signals were identified.

“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 [liso-cel] 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 Bristol Myers Squibb, stated in a news release. “This is another important step in our commitment to delivering [liso-cel] to more patients across indications, as well as expanding into new regions, especially for diseases with continued unmet need such as relapsed or refractory follicular lymphoma, which is considered incurable.”

In May 2024, the FDA granted accelerated approval to liso-cel for the treatment of adult patients with relapsed/refractory follicular lymphoma who have received 2 or more prior lines of systemic therapy.2 This regulatory decision was also supported by data from TRANSCEND FL.

The open-label, single-arm, multi-cohort, multicenter study enrolled patients at least 18 years of age with histologically confirmed relapsed/refractory grade 1, 2 or 3a follicular lymphoma or marginal zone lymphoma.3 At least 2 prior lines of therapy were required, and 1 line needed to include an anti-CD20 monoclonal antibody and an alkylating agent; however, patients with follicular lymphoma with high-risk features were allowed to enroll after 1 prior line of therapy. Other key inclusion criteria consisted of an ECOG performance status of 0 or 1 and adequate organ function.

Patients were excluded if they had evidence or history of composite diffuse large B-cell lymphoma and follicular lymphoma, transformed follicular lymphoma, or duodenal-type follicular lymphoma; central nervous system involvement; prior treatment with a CAR T-cell therapy; active autoimmune disease requiring immunosuppressive therapy; acute or chronic graft-vs-host disease; or a history of significant cardiovascular disease.

Following leukapheresis, enrolled patients underwent lymphodepleting chemotherapy consisting of fludarabine at 30 mg/m2 and cyclophosphamide at 300 mg/m2 for 3 days. Patients received liso-cel at a target dose of 100 × 106 CAR-positive T cells 2 to 7 days after completing lymphodepletion.

ORR served as the trial’s primary end point. Secondary end points included CR rate, DOR, duration of CR, progression-free survival, overall survival, safety, and quality of life.

Among patients with non-Hodgkin lymphoma treated with the liso-cel across clinical trials evaluating the CAR T-cell therapy (n = 702), any-grade cytokine release syndrome (CRS) was reported in 54% of patients, including 3.2% who had grade 3 or higher CRS.1 The median time to onset of CRS was 5 days (range, 1-63). CRS resolved in 98% of patients at a median of 5 days (range, 1-37). Grade 5 CRS was reported in 1 patient, and 5 patients had ongoing CRS at the time of death.

The European Commission will now review the CHMP recommendation, and a decision on potential approval is expected approximately 2 months following the CHMP recommendation.

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 January 31, 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. FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. FDA. May 15, 2024. Accessed January 31, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma
3. A study to evaluate the efficacy and safety of JCAR017 in adult subjects with relapsed or refractory indolent B-cell non-Hodgkin lymphoma (NHL) (TRANSCEND FL). ClinicalTrials.gov. Updated January 15, 2025. Accessed January 31, 2025. https://classic.clinicaltrials.gov/ct2/show/NCT04245839