Liso-Cel Generates Responses in R/R Marginal Zone Lymphoma

Lisocabtagene maraleucel (Liso-cel; Breyanzi) elicited a statistically significant and clinically meaningful overall response rate (ORR) in adult patients with relapsed/refractory marginal zone lymphoma (MZL), meeting the primary end point of the MZL cohort of the phase 2 TRANSCEND FL trial (NCT04245839).1

The trial also met its key secondary end point of complete response (CR) rate in this cohort. A topline analysis showed that responses were durable, and the safety profile of liso-cel was consistent with prior findings for the CAR T-cell therapy with no new safety signals reported.

“MZL is a slow-growing cancer that, for many, has a favorable prognosis. [However,] for those patients who relapse or become refractory, the disease can be quite aggressive, and there is a need for new effective and tolerable treatment options to address this unmet critical need,” Rosanna Ricafort, vice president and head of the Late Development Program Leadership, Hematology and Cell Therapy, at Bristol Myers Squibb, stated in a news release. “We are pleased that the TRANSCEND FL study supports the potential of [liso-cel] in MZL and look forward to presenting detailed results from the study at an upcoming medical meeting.”

TRANSCEND FL MZL Cohort Study Design

The open-label, multicenter, single-arm TRANSCEND FL trial is investigating the efficacy and safety of liso-cel in patients with relapsed/refractory indolent B-cell non-Hodgkin lymphoma, including follicular lymphoma (FL) and MZL.2 To be eligible for enrollment in the MZL cohort, patients must have had MZL that was histologically confirmed within 6 months of screening, as assessed by local pathology; prior treatment with at least 2 lines of systemic therapy that included an anti-CD20 and alkylating agent, or relapse after hematopoietic stem cell transplant; an ECOG performance status of 0 or 1; adequate organ function; and adequate vascular access for leukapheresis.

Patients received lymphodepleting chemotherapy with intravenous (IV) fludarabine at 30 mg/m2 plus IV cyclophosphamide at 300 mg/m2 for 3 days prior to liso-cel infusion. Liso-cel was administered on day 1 at a target dose of 100 x 106 CAR-positive viable T cells 2 to 7 days after completion of lymphodepleting chemotherapy.

Additional secondary end points include duration of response (DOR), progression-free survival, overall survival, pharmacokinetics, and quality of life.

Outcomes From the FL Cohort

Liso-cel is currently FDA approved for the treatment of adult patients with relapsed/refractory FL who have received at least 2 prior lines of systemic therapy, including an anti-CD20 antibody and an alkylating agent.3 This regulatory decision was supported by findings from the FL cohort of TRANSCEND FL, in which patients who received liso-cel (n = 94) achieved an ORR of 95.7% (95% CI, 89.5%-98.8%). Furthermore, at a median follow-up of 16.8 months (95% CI, 16.3-17.0), the median DOR was not yet reached (NR; 95% CI, 18.04-NR).

At a data cutoff date of January 27, 2023, and a median follow-up of 18.9 months (range, 0.3-28.2), additional findings showed patients in the FL cohort who received liso-cel in the third line or later experienced an ORR of 97% (95% CI, 91.6%-99.4%; P < .0001) and a CR rate of 94% (95% CI, 87.5%-97.8%; P < .0001).4

Regarding safety, the most common adverse effects were cytokine release syndrome (CRS), headache, musculoskeletal pain, fatigue, constipation, and fever.3 The FDA approval of liso-cel for patients with FL included a Risk Evaluation and Mitigation Strategy due to the agent’s associated risk of fatal or life-threatening CRS and neurologic toxicities.

The recommended dose of liso-cel in patients with FL is 90 x 106 to 110 x 106 CAR-positive viable T-cells with a 1:1 ratio of CD4 and CD8 components.

References

1. Bristol Myers Squibb announces positive topline results for Breyanzi (lisocabtagene maraleucel) in adult patients with relapsed or refractory marginal zone lymphoma. News release. Bristol Myers Squibb. February 10, 2025. Accessed February 10, 2025. https://news.bms.com/news/corporate-financial/2025/Bristol-Myers-Squibb-Announces-Positive-Topline-Results-for-Breyanzi-lisocabtagene-maraleucel-in-Adult-Patients-with-Relapsed-or-Refractory-Marginal-Zone-Lymphoma/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 November 30, 2023. Accessed May 15, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT04245839
3. FDA grants accelerated approval to lisocabtagene maraleucel for follicular lymphoma. FDA. May 15, 2024. Accessed February 10, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lisocabtagene-maraleucel-follicular-lymphoma
4. Morschhauser F, Dahiya S, Palomba ML, et al. Lisocabtagene maraleucel in follicular lymphoma: the phase 2 TRANSCEND FL study. Nat Med. 2024;30(8):2199-2207. doi:10.1038/s41591-024-02986-9