Liso-Cel Receives European Approval in Relapsed/Refractory Follicular Lymphoma

The European Commission (EC) has expanded the approval of lisocabtagene maraleucel (liso-cel; Breyanzi) to include the treatment of adult patients with relapsed/refractory follicular lymphoma following at least 2 prior lines of systemic therapy.1

The regulatory decision was supported by data from the phase 2 TRANSCEND FL study (NCT04245839), which examined liso-cel in adult patients with relapsed/refractory indolent B-cell non-Hodgkin lymphoma, including follicular lymphoma. Data from TRANSCEND FL presented during the 2024 ASH Annual Meeting showed that at a median follow-up of 30.0 months (range, 0.3-39.6), efficacy-evaluable patients treated in the third line or later (n = 103) achieved an overall response rate (ORR) of 97.1% (95% CI, 91.7%-99.4%), with a complete response (CR) rate of 94.2% (95% CI, 87.8%-97.8%).2 The median time to first response was 0.95 months (range, 0.6-3.3) and 75.7% (95% CI, 66.0%-83.0%) of patients remained in response at 18 months.1

“This additional approval for [liso-cel] in follicular lymphoma represents a critical step forward in our mission to deliver on the transformational promise of cell therapy for more patients across Europe,” Emma Charles, senior vice president, Europe Region, Bristol Myers Squibb, stated in a news release. “While significant advancements have been made in the last 2 decades, there still remains unmet need for patients. Newer treatments for follicular lymphoma, like [liso-cel], have shown impactful results in clinical trials, with the opportunity to deliver lasting results in the routine care setting.”

TRANSCEND FL was an open-label, global, multicenter, single-arm study that enrolled adult patients with relapsed/refractory grade 1, 2, or 3a follicular lymphoma or marginal zone lymphoma (MZL).3 Patients were required to have received at least 1 prior therapy, including an anti-CD20 and alkylating agent; have an ECOG performance status of 0 or 1; have adequate organ function; and have adequate vascular access for leukapheresis. Patients with follicular lymphoma needed to have high-risk disease, and those with MZL needed to have received 2 or more prior lines of therapy or have relapsed after hematopoietic stem cell transplant.

Eligible patients received intravenous (IV) fludarabine at a dose of 30 mg/m2 per day and 300 mg/m2 of IV cyclophosphamide per day for 3 days prior to liso-cel infusion. Liso-cel was then administered at a target dose of 100 × 106 CAR-positive viable T cells 2 to 7 days following completion of lymphodepleting chemotherapy.

The primary end point was ORR. Secondary end points included CR rate, duration of response (DOR), progression-free survival (PFS), overall survival (OS), safety, pharmacokinetics, and quality of life measures.

Additional findings from TRANSCEND FL demonstrated that, at a median follow-up of 29.5 months (range, 1.0-38.2), efficacy-evaluable patients in the second line of treatment and beyond (n = 23) achieved an ORR and CR rate of 95.7% (95% CI, 78.1%-99.9%).2 The 24-month DOR, PFS, and OS rates were 86.4% (95% CI, 63.4%-95.4%), 82.6% (95% CI, 60.1%-93.1%), and 95.7% (95% CI, 72.9%-99.4%), respectively. In the third line and beyond group, these respective rates were 74.6% (95% CI, 64.8%-82.1%), 72.5% (95% CI, 62.7%-80.1%), and 88.2% (95% CI, 80.1%-93.1%).

In terms of safety, findings for liso-cel were consistent with the already established safety profile with no new signals in patients with follicular lymphoma.1 Among all patients treated in the second line and beyond, any-grade cytokine release syndrome (CRS) occurred at a rate of 58%, with 0.8% of patients experiencing grade 3 CRS. The median time to onset of CRS was 6 days (range, 1-17). Any-grade and grade 3 neurologic toxicities occurred at rates of 16% and 3%, respectively. The median time to onset of the first neurotoxicity was 8 days (range, 4-16).

The expanded approval of liso-cel by the EC applies to all European Union (EU) member states, as well as Iceland, Norway, and Liechtenstein. The agent is also approved in the EU for the treatment of adult patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL) and follicular lymphoma grade 3B, who relapsed within 12 months from completion of, or are refractory to, frontline chemoimmunotherapy. Liso-cel is also approved in the EU for the treatment of adult patients with relapsed/refractory DLBCL, PMBCL, and follicular lymphoma grade 3 following at least 2 lines of systemic therapy.

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.4 This regulatory decision was also supported by data from TRANSCEND FL.

References

1. Bristol Myers Squibb receives approval from the European Commission to expand use of CAR T cell therapy Breyanzi for relapsed or refractory follicular lymphoma. News release. Bristol Myers Squibb. March 14, 2025. Accessed March 14, 2025. https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Receives-Approval-from-the-European-Commission-to-Expand-Use-of-CAR-T-Cell-Therapy-Breyanzi-for-Relapsed-or-Refractory-Follicular-Lymphoma/default.aspx
2. Nastoupil L, Dahiya S, Lia M, et al. Lisocabtagene maraleucel (liso-cel) in patients (pts) with relapsed or refractory (R/R) follicular lymphoma (FL): Transcend FL 2-year follow-up. Blood. 2024;144(suppl 1):4387. doi:10.1182/blood-2024-198509
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 February 19, 2025. Accessed March 14, 2025. https://clinicaltrials.gov/study/NCT04245839
4. FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. FDA. May 15, 2024. Accessed March 14, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma