Lisocabtagene maraleucel (Breyanzi; liso-cel) demonstrated exceptional efficacy in patients with relapsed/refractory marginal zone lymphoma (MZL), achieving a 95.5% overall response rate in the MZL cohort of the phase 2 TRANSCEND FL trial, according to Bristol Myers Squibb. The results represent a significant breakthrough for patients with this hard-to-treat indolent lymphoma.
Robust Clinical Outcomes
Among 66 evaluable patients with relapsed/refractory MZL who received liso-cel, the overall response rate by independent review committee assessment was 95.5% (95% CI, 87.3%-99.1%; P <.0001). Notably, 62.1% of patients achieved a complete response (95% CI, 49.3%-73.8%; P <.0001), demonstrating the therapy's ability to induce deep remissions.
The durability of responses proved equally impressive. After a median follow-up of 21.6 months, the 24-month duration of response rate was 88.6%. Long-term survival outcomes showed 24-month progression-free survival and overall survival rates of 85.7% and 90.4% at median follow-ups of 23.8 months and 24.5 months, respectively.
Addressing Critical Unmet Need
"Liso-cel achieved high, lasting response rates in patients with relapsed/refractory MZL, underscoring the potential of this one-time therapy to significantly improve patient outcomes," said study investigator M. Lia Palomba, MD, lymphoma and cell therapy specialist at Memorial Sloan Kettering Cancer Center. "Currently, the median OS for patients with MZL with progression after multiple lines of therapy is 3 to 5 years, signifying an urgent need for transformative therapies that can effectively address this hard-to-treat disease."
Trial Design and Patient Population
The TRANSCEND FL trial is an open-label, single-arm, multicohort, multicenter study evaluating liso-cel in patients with relapsed/refractory follicular lymphoma or MZL. For the MZL cohort, patients required at least 2 prior lines of systemic therapy or relapse following hematopoietic stem cell transplant, with at least one prior line featuring an anti-CD20 antibody and an alkylating agent.
Patients underwent leukapheresis for liso-cel manufacturing before receiving lymphodepleting chemotherapy comprising 30 mg/m² of intravenous fludarabine per day and 300 mg/m² of intravenous cyclophosphamide daily for 3 days. A single liso-cel infusion at a target dose of 100 × 10⁶ CAR-positive T cells was administered 2 to 7 days later.
Favorable Safety Profile
The safety profile of liso-cel remained consistent with previous reports, with low rates of severe cytokine release syndrome (CRS) and neurological events. Any-grade CRS occurred in 76% of patients, with only 4% experiencing grade 3 CRS events and no grade 4/5 events observed. Neurological events showed any-grade, grade 3, and grade 4/5 rates of 33%, 4%, and 0%, respectively.
"MZL is an indolent disease but remains an area of high unmet need for patients who are relapsing and reaching later lines of treatment," stated Rosanna Ricafort, vice president and senior global program lead for Hematology and Cell Therapy at Bristol Myers Squibb. "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."
The comprehensive results will be presented at the 2025 International Conference on Malignant Lymphoma in an oral presentation on June 19, building upon topline results announced in February.
