In R/R Marginal Zone Lymphoma, 90% Alive at 2 Years After Liso-Cel

Lisocabtagene maraleucel (liso-cel), the chimeric antigen receptor (CAR) T-cell therapy sold as Breyanzi, produced responses in more than 95% of patients with relapsed or refractory marginal zone lymphoma (MZL) in recent trial, with more than 90% of them alive after 2 years.

Results for the MZL arm of the phase 2 study, TRANSCEND FL, were presented June 19 at the International Conference on Malignant Lymphoma, which took place in Lugano, Switzerland. Bristol Myers Squibb, the developer of liso-cel, reported the results in a statement.

MZL is among the blood cancers that fall under the umbrella of non-Hodgkin lymphoma (NHL). The cancer derives its name from the marginal zone of lymphoid tissue, where it slowly develops from B cells. According to Cleveland Clinic, symptoms include fever, night sweats, and weight loss, which can be followed by nausea and stomach pain, fatigue, and for some patients, an enlarged spleen.

Liso-cel is already approved to treat other types of R/R NHL: diffuse large B-cell lymphoma, mantle cell lymphoma, follicular lymphoma, and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). 

Topline results from TRANSCEND FL (NCT04245839), announced earlier this year, suggested MZL could join the list of blood cancers treated with liso-cel, which would be the most of any CD19-directed CAR T-cell therapy. The 66 patients in the MZL cohort, all in at least the third line of treatment, received a target dose of 100 x 10⁶ CAR-positive viable T cells.

The study met both its primary end point of overall response rate (ORR) as well as a key secondary end point, complete response rate (CRR). Results, evaluated by an independent review committee, were as follows:

• 95.5% of patients treated with liso-cel after at least 2 prior therapies achieved a response (ORR) (95% CI, 87.3%-99.1%; one-sided P < .0001).
• 62.1% achieved a CR, and 88.6% maintained a response at 24 months (95% CI, 49.3%-73.8%; one-sided P < .0001).
• With a median follow-up of 24.5 months, the 2-year overall survival (OS) rate for patients treated with liso-cel was 90.4%.
• Patients with MZL had a safety profile consistent with prior trials of the therapy, with no new signals reported.

“Liso-cel achieved high, lasting response rates in patients with relapsed or refractory marginal zone lymphoma, underscoring the potential of this one-time therapy to significantly improve patient outcomes,” investigator M. Lia Palomba, MD, a lymphoma and cell therapy specialist at Memorial Sloan Kettering Cancer Center, said in the BMS statement. “Currently, the median survival for patients with marginal zone lymphoma with multiple relapses is 3 to 5 years, signifying an urgent need for transformative therapies that can effectively address this hard-to-treat disease.”

Cytokine release syndrome (CRS) was seen in 76% of patients, with 4% experiencing grade 3 CRS, and none experienced grade 4 or grade 5. Neurological events (NEs) were seen in 33% of patients, with 4% experiencing grade 3 NEs. None experienced grade 4 or grade 5 NEs.

Rosanna Ricafort, vice president, Senior Global Program Lead for Hematology and Cell Therapy, Bristol Myers Squibb, said the results show liso-cel can address an unmet need in MZL.

“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.”

Reference

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 24, 2025. https://bit.ly/3G32EmP