CART19-BE-02 phase II trial: Varnimcabtagene autoleucel for R/R B-ALL

Results from the multicenter, single-arm, phase II CART19-BE-02 trial (NCT04778579) evaluating varnimcabtagene autoleucel (var-cel), an autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy with adaptive intra-patient dose escalation, in 38 adult patients with relapsed/ refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) were recently published in The Lancet Haematology by Ortiz-Maldonado et al. The primary endpoint was complete response with undetected measurable residual disease (MRD). 

Key data: At a median follow-up from infusion of 8.6 months, a complete response (CR) with undetected measurable residual disease (MRD) was demonstrated by 84.4% of patients who received at least one dose of var-cel (n = 32). Treatment-emergent adverse events (TEAEs) occurred in 94% of patients (n = 33). The most common Grade ≥3 TEAEs were neutropenia (45%), thrombocytopenia (21%), anemia (15%), and cytokine release syndrome (CRS; 12%). Immune effector cell-associated neurotoxicity syndrome and cerebral edema occurred in one patient (Grade ≥3), and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome occurred in two patients.

Key learning: Results suggest that var-cel induces deep remission with low incidence of severe CRS and any-grade immune effector cell-associated neurotoxicity syndrome, supporting fractionated dose escalation as a strategy.