Varnimcabtagene autoleucel (ARI-0001) in relapsed or refractory mantle cell lymphoma

Varnimcabtagene autoleucel (var-cel) is an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy administered using an adaptive, fractionated dosing strategy. We conducted a multicenter retrospective study to evaluate the safety and efficacy of var-cel in patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) treated at four Spanish centers, including patients enrolled in the CART19-BE-01 trial and a subsequent compassionate use program. Thirty patients underwent leukapheresis; 27 received var-cel following lymphodepletion and fractionated infusion in three escalating doses (0.1 to 5 × 10⁶ CAR T cells/kg). Any-grade cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 93% and 4%, respectively, with Grade ≥3 CRS and/or ICANS observed in a single patient (4%). The overall response rate among infused patients was 89% (95% CI, 71-98), including 78% complete responses (95% CI, 58-91). Median duration of response and progression-free survival were 17.1 and 15.4 months, respectively. With a median follow-up of 21.7 months, median overall survival was 35.2 months. In this multicenter academic experience, var-cel demonstrated high antitumor activity with low rates of severe CRS and ICANS, supporting its use within a coordinated national network.