Liso-cel Exhibits High Durable Response Rates in R/R Marginal Zone Lymphoma
No new safety signals were observed with liso-cel, with the therapy showing low rates of severe cytokine release syndrome and neurologic events.
At median follow-ups of 23.8 months and 24.5 months, the 24-month progression-free survival and overall survival rates were 85.7% and 90.4%, respectively.
Lisocabtagene maraleucel (Breyanzi; liso-cel) demonstrated sustained, clinically meaningful efficacy in patients with relapsed/refractory marginal zone lymphoma (MZL), according to a news release on findings from the MZL cohort of the single-arm phase 2 TRANSCEND FL trial (NCT04245839) from the drug’s developer, Bristol Myers Squibb.1
New data from the trial will be presented at the 2025 International Conference on Malignant Lymphoma (ICML) in an oral presentation on June 19. These data build upon topline results announced in February.2
According to the news release, among evaluable patients with relapsed/refractory MZL who received liso-cel (n = 66), the overall response rate (ORR) by independent review committee assessment was 95.5% (95% CI, 87.3%-99.1%; P <.0001), and 62.1% of patients achieved a complete response (CR; 95% CI, 49.3%-73.8%; P <.0001). Additionally, after a median follow-up of 21.6 months, the 24-month rate for duration of response (DOR) was 88.6%. At median follow-ups of 23.8 months and 24.5 months, the 24-month progression-free survival (PFS) and overall survival (OS) rates were 85.7% and 90.4%, respectively.
“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,” study investigator M. Lia Palomba, MD, lymphoma and cell therapy specialist at Memorial Sloan Kettering Cancer Center, said in the news release.1 “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.”
Results from the phase 2 study previously published in Nature in June 2024 showed that 139 patients with relapsed or refractory indolent non-Hodgkin lymphoma were enrolled on the trial.3 Those treated either received liso-cel as third- or fourth-line therapy (n = 114) or second-line therapy (n = 25) after disease progression at 24 or fewer months following diagnosis (POD24) and prior treatment with an anti-CD20 antibody and alkylating agent at less than 6 months after initial diagnosis (45%). Most patients also met at least 1 metastatic Groupe d’Etude des Lymphomes Folliculaires (mGELF) criterion (56%).
Those enrolled initially underwent leukapheresis for liso-cel manufacturing before being treated with 30 mg/m2 of intravenous fludarabine per day and 300 mg/m2 of intravenous cyclophosphamide daily for 3 days (LDC). A single liso-cel infusion at a target dose of 100 x 106 CAR-positive T cells was given 2 to 7 days later, with optional bridging therapy permitted for disease control. Reconfirmation of PET/CT-positive disease was required before LDC.
Patients had a median age of 60 years (range, 23-80); 64% were male, 53% were White, and 35% had an unknown race. A total of 63% of patients had an ECOG performance status of 0 at screening, 75% had grade 1 or 2 follicular lymphoma, and 52% had Ann Arbor stage IV disease. Additionally, there was a median of 2 prior lines of therapy (range, 1-10), and 38% of patients received bridging therapy.
The primary study end point was ORR per independent review committee by PET/CT. Secondary end points included CR rate, DOR, PFS, OS, and safety.
According to the press release, the safety profile of liso-cel was consistent with previous reports, with low rates of severe cytokine release syndrome (CRS) and neurological events, and no new safety signals observed. Any-grade CRS occurred in 76% of patients, with 4% of patients experiencing grade 3 CRS events; there were no observed grade 4/5 events. Additionally, the any-grade, grade 3, and grade 4/5 rates for neurological events were 33%, 4%, and 0%.
References
- 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). Bristol Myers Squibb. News release. June 16, 2025. Accessed June 16, 2025. https://tinyurl.com/3s32tacc
- 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 June 16, 2025. https://tinyurl.com/382esjk9
- 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
Highlighting Insights From the Marginal Zone Lymphoma Workshop
Clinicians outline the significance of the MZL Workshop, where a gathering of international experts in the field discussed updates in the disease state.
