Dr Shah on Efficacy Data for Zamto-Cel in R/R DLBCL

Despite some of these poor prognostic indicators, we were happy to report that the overall response rate was [72.8%,] with [50.8%] of patients achieving a complete remission, Many of these remissions were durable."

Nirav Shah, MD, MSHP, associate professor of medicine, at the Medical College of Wisconsin, discusses interim findings from the phase 2 DALY II USA trial (NCT04792489) evaluating zamtocabtagene autoleucel (Zamto-cel; MB-CART2019.1), a dual CD19- and CD20-directed non-cryopreserved CAR T-cell therapy, in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data were presented at the 2025 Transplantation & Cellular Therapy Meetings.

The analysis included 59 evaluable patients in the modified intention-to-treat population. Shah notes that many patients had high-risk disease, as indicated by elevated International Prognostic Index (IPI) scores and lactate dehydrogenase (LDH) levels at enrollment. Despite these adverse prognostic factors, the overall response rate (ORR) was 72.8%, including a complete remission (CR) rate of 50.8%. The median duration of response was 11.4 months; for patients achieving a CR, the median duration of CR was not yet reached at the time of analysis.

At 6 months, the progression-free survival (PFS) rate was 55%, and the median PFS was 9.0 months. The median overall survival (OS) had not been reached.

Shah explains that continued follow-up will be vital to record more mature data. Future analyses will examine 1- and 2-year outcomes for patients treated during the study.

The safety profile of zamto-cel was favorable, with no cases of grade 3 or higher cytokine release syndrome (CRS) reported. Immune effector cell–associated neurotoxicity syndrome (ICANS) of grade 3 or higher occurred in 4.3% of patients.

Notably, dual CD19/CD20 targeting was associated with a potential mitigation of antigen loss as a resistance mechanism. Among 27 patients who had disease progression, no antigen loss was observed in 22 patients. CD19 loss and CD20 loss were experienced by 2 patients each, and 1 patient had dual CD19/CD20 loss.