Dr Shah on the Clinical Implications and Future Directions of Zamto-Cel in R/R DLBCL

“What you're seeing would be the first next-generation CAR T-cell therapy available. To highlight the differentiators of this product, number 1, it’s not just CD-19, but it's CD-19 plus CD-20–targeting. Number 2, it’s rapid manufacturing, so patients get [the fresh product] within 14 days.”

Nirav Shah, MD, an associate professor of medicine in the Division of Hematology and Oncology at the Medical College of Wisconsin, discussed the clinical implications and the future directions of data from the phase 2 DALY II USA study (NCT04792489) evaluating zamtocabtagene autoleucel (zamto-cel; MB-CART2019.1) for the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL).

The phase 2 study based in the United States assessed the efficacy and safety of third-line zamto-cel in a difficult-to-treat patient population with relapsed/refractory DLBCL, Shah began. He noted that in Europe, a similar trial is evaluating zamto-cel as second-line therapy for transplant-ineligible patients with DLBCL in a randomized control setting. Following the results of these 2 trials, Shah explained that he hopes regulatory approval will follow in the future.

When and if zamto-cel receives approval, Shah added that it would mark the first next-generation CAR T-cell therapy commercially available. He emphasized that there are 2 main differentiators between zamto-cel and previously approved CAR T-cell therapy. First, zamto-cel is targets both CD-19 and CD-20. Second, it is rapidly manufactured, meaning patients can receive the fresh product within 14 days of harvesting. Previous data had suggested that freezing CAR T cells before administration could be detrimental to the CAR T-cell therapy, which is why fresh administration may be warranted, he said.

Data from the study, which were presented at the 2025 Transplant & Cellular Therapy Meetings, showed that patients with DLBCL in the modified intent-to-treat population (n = 59) achieved an overall response rate (ORR) of 72.8%, of which 50.8% were complete remissions (CR), and responses were observed across patient subgroups. Specifically, patients who experienced the highest CR rates included those who relapsed after their last line of therapy (82%; n = 9), those who underwent prior autologous stem cell transplant (64%; n = 9), and those who were previously treated with at least 3 lines of therapy (60%; n = 9).

With efficacy and safety data seen with zamto-cel in the study’s patient population, it could be provided to patients of any age, Shah said. He concluded that it could also be potentially given in an outpatient setting, considering there is no evidence of grade 3 or greater cytokine release syndrome.