Abstract Here we presented the safety and efficacy of a novel CD19 CAR-T, named IM19, in relapsed/refractory mantle cell lymphoma (r/r MCL) patients in an open-label, single-arm phase I trial. IM19 is featured with an innovative CAR molecule with a protective peptide at the N-terminus and the 4-1BB co-stimulatory domain, and a DuraCART manufacturing process generating the CAR-T formulation with over 80% of lowly differentiated T cells. A total of eleven r/r MCL patients were recruited and received a single or twice infusion of IM19 with dose-escalation from 1*108 to 2*108CAR-T cells after three-day conditional regimen of fludarabine (30mg/m2) and cyclophosphamide (300 mg/m2). The primary endpoints were to evaluate the safety, tolerability, the incidence of dose-limiting-toxicity (DLT), and 3-month overall response rate (ORR) of IM19. Complete response (CR) and best ORR were evaluated as secondary objectives.

In this study, five patients were treated with a dose of 1*108 CAR-T cells (DL1 group), and two of them received a secondary infusion. Six patients were treated with a dose of 2*108 CAR-T cells (DL2 group) and received only a single infusion. The 3-month ORR was 81.8%, and the median progression-free survival and overall survival rate were not reached. CR was observed in 10/11 (90.9%) patients. In the DL1 group, all the patients achieved CR at one month (100%), and only one case who received a secondary infusion progressed at three months. In the DL2 group, CR was observed in 5/6 (83.3%) patients, all of whom showed durable response at three months. Grade 1-2 cytokine release syndrome was observed in 5/11 (45.5%) patients, and no grade 3-4 CRS occurred. One patient developed grade 2 neurotoxicity, with an incidence rate of 9.1%. In all cases, CAR-T cell expansion in the peripheral blood was observed after the single or first infusions. However, the expansion was incompetent after the second infusions. In summary, IM19 showed good tolerability and efficacy for r/r MCL at doses of 1*108 and 2*108CAR-T cells, and a secondary infusion was unbeneficial for improvement of the efficacy.

Key words: r/r MCL; CD19 CAR-T; Safety; Efficacy

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2025
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