Liso-Cel Yields Durable Responses in R/R Marginal Zone Lymphoma

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Treatment with lisocabtagene maraleucel (liso-cel; Breyanzi) led to deep and durable responses in patients with relapsed/refractory marginal zone lymphoma (MZL), according to primary results from the MZL cohort of the phase 2 TRANSCEND FL trial (NCT04245839).1

Findings announced by Bristol Myers Squibb showed that patients with MZL treated with liso-cel (n = 66) achieved an overall response rate (ORR) of 95.5% (95% CI, 87.3%-99.1%; one-sided P < .0001). The complete response (CR) rate was 62.1% (95% CI, 49.3%-73.8%; one-sided P <0.0001) based on CT scans per independent review committee assessment.

The 24-month duration of response (DOR) rate was 88.6% at a median follow-up of 21.6 months; the 24-month progression-free survival (PFS) rate was 85.7% at a median follow-up of 23.8 months; and the 24-month overall survival (OS) rate was 90.4% at a median follow-up of 24.5 months.

Data are also being presented at the 18th Annual International Conference on Malignant Lymphoma (ICML) in June.

“Liso-cel achieved high, lasting response rates in patients with relapsed or refractory MZL, underscoring the potential of this one-time therapy to significantly improve patient outcomes,” M. Lia Palomba, MD, TRANSCEND FL study investigator and lymphoma and cell therapy specialist at Memorial Sloan Kettering Cancer Center in New York, New York, stated in a news release. “Currently, the median [OS] for patients with MZL with multiple relapses is 3 to 5 years, signifying an urgent need for transformative therapies that can effectively address this hard-to-treat disease.”

TRANSCEND FL Background and MZL Cohort Deep Dive

TRANSCEND FL is an open-label, single-arm, multicohort, multicenter study evaluating liso-cel in patients with relapsed/refractory follicular lymphoma or MZL.2 Notably, prior data from the trial supported the May 2024 FDA accelerated approval liso-cel for the treatment of adult patients with relapsed/refractory follicular lymphoma who have received 2 or more prior lines of systemic therapy.3

Investigators enrolled patients with relapsed/refractory grade 1, 2, or 3a follicular lymphoma or MZL that was histologically confirmed within 6 months of screening.2 At least one prior line of therapy featuring an anti-CD20 antibody and an alkylating agent was required for all patients.

Patients with follicular lymphoma were allowed to enroll if they received 2 or more prior lines of systemic therapy; notably, patients with follicular lymphoma with high-risk features were allowed to participate if they received only 1 prior line of therapy.

At least 2 prior lines of systemic therapy or relapse following hematopoietic stem cell transplant was required for patients with MZL. Other inclusion criteria for all patients included an ECOG performance status of 0 or 1, and adequate organ function and vascular access for leukapheresis.

Patients with evidence or a history of composite diffuse large B-cell lymphoma and follicular lymphoma, or a history of transformed follicular lymphoma, were not allowed to enroll. Duodenal-type follicular lymphoma also prevented patients from participating.

After leukapheresis, patients underwent lymphodepleting chemotherapy comprising fludarabine at 30 mg/m2 per day and cyclophosphamide at 300 mg/m2 per day for 3 days prior to CAR T-cell therapy. Liso-cel was given on day 1 at a target dose of 100 × 106 CAR-positive viable T cells. CAR T-cell therapy infusion occurred 2 to 7 days after the end of lymphodepletion.

ORR served as the trial’s primary end point. Secondary end points included CR rate, DOR, PFS, OS, safety, and pharmacokinetics.

Safety data from the MZL cohort showed that no new safety signals were reported.1 The rate of any-grade cytokine release syndrome was 76%; the rate of grade 3 CRS was 4%, and no grade 4/5 instances were reported. Any-grade neurotoxicity occurred in 33% of patients; the grade 3 rate was 4%, and no grade 4/5 neurotoxicities were reported.

“MZL is an indolent disease but remains an area of high unmet need for patients who are relapsing and reaching later lines of treatment,” Rosanna Ricafort, vice president and senior global program lead for Hematology and Cell Therapy at Bristol Myers Squibb, stated in a news release. “We are proud to present for the first time the primary analysis data from the MZL cohort of TRANSCEND FL, underscoring our commitment to unlock the full potential of cell therapy to help patients living with relapsed or refractory lymphomas. As highlighted by the data at ICML, [liso-cel] continues to cover the broadest patient eligibility of any CAR [T-cell therapy] for B-cell malignancies and demonstrates a safety profile consistent with clinical trials and in the real-world setting for approved indications.”

References

1. Bristol Myers Squibb presents first data from the marginal zone lymphoma cohort of the Transcend FL trial demonstrating deep and durable responses with Breyanzi (lisocabtagene maraleucel). News release. Bristol Myers Squibb. June 16, 2025. Accessed June 16, 2025. https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Presents-First-Data-from-the-Marginal-Zone-Lymphoma-Cohort-of-the-Transcend-FL-Trial-Demonstrating-Deep-and-Durable-Responses-with-Breyanzi-lisocabtagene-maraleucel/default.aspx
2. 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 May 23, 2025. Accessed June 16, 2025. https://clinicaltrials.gov/study/NCT04245839
3. FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. FDA. May 15, 2024. Accessed June 16, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma