Dr Shah on Zamtocabtagene Autoleucel’s Favorable Safety Profile in R/R DLBCL

"One of the concerns when you target more than 1 protein is whether you are going to see more toxicity; the answer to that question [in this trial was] a clear and resounding no...We’re very satisfied and excited by the safety profile [of zamto-cel], which, in combination with the rapid manufacturing and dual targeting of more than 1 cell protein,really makes this product a viable treatment option.”

Nirav Shah, MD, MSHP, an associate professor of medicine in the Division of Hematology and Oncology at the Medical College of Wisconsin, discussed interim safety findings from the phase 2 DALY II USA trial (NCT04792489), which evaluated 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). These findings were presented at the 2025 Transplantation & Cellular Therapy Meetings.

The trial assessed the safety profile of the dual-targeted CAR T-cell therapy, with a focus on cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Shah emphasized that concerns regarding the potential for increased toxicity with dual-antigen targeting therapy were not supported by the data from this trial. No patients experienced grade 3 or higher CRS, defined by the need for vasopressor support. Furthermore, grade 3 or higher ICANS was reported in only 4.3% of patients, suggesting that zamto-cel hasa favorable safety profile compared with other CAR T-cell therapies.

These findings highlight the potential of zamto-cel as a viable treatment option for patients with relapsed/refractory DLBCL, should it receive regulatory approval, Shah explains. The combination of dual B-cell antigen targeting with a non-cryopreserved manufacturing process offers potential advantages, including rapid manufacturing timelines, which may also improve accessibility for patients with aggressive disease, according to Shah.

Shah concludes that the interim safety analysis of DALY II USA supports further investigation into the efficacy and long-term safety of zamto-cel.