Nirav Shah, MD, MSHP, on Evaluating Zamto-Cel in R/R DLBCL

This article originally appeared on our sister site, OncLive®.

"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."

Zamtocabtagene autoleucel (zamto-cel; MB-CART2019.1), a dual CD19- and CD20-directed noncryopreserved chimeric antigen receptor T-cell (CAR-T) therapy, is currently being evaluated in the phase 2 DALY II USA trial (NCT04792489) for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Interim data from this study were recently presented at the 2025 Tandem Meetings |Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR, held in Honolulu, Hawaii, February 12 to 15, 2025.

During the meeting, CGTLive®'s sister site OncLive®, interviewed Nirav Shah, MD, MSHP, an associate professor of medicine at Medical College of Wisconsin, about the analysis, which included 59 evaluable patients in the modified intention-to-treat population. Shah pointed out that many of these patients had elevated International Prognostic Index (IPI) scores and lactate dehydrogenase (LDH) levels at enrollment, indicating high-risk disease. Although, the overall response rate (ORR) was 72.8%, including a complete remission (CR) rate of 50.8%, despite the adverse prognostic factors. Furthermore, an 11.4 month median duration of response was recorded, and for patients achieving a CR, the median duration of CR was not yet reached as of the data cut-off.

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 explained that continued follow-up will be vital to obtain more mature data. Future analyses will examine the 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 reported. Immune effector cell–associated neurotoxicity syndrome 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.

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