Anbalcabtagene autoleucel (PD-1 and TIGIT knockdown CD19 CAR-T) for relapsed/refractory large B-cell lymphoma...

Anbalcabtagene autoleucel (Anbal-cel) is a CD19-directed CAR T-cell therapy incorporating dual PD-1 and TIGIT knockdown to enhance antitumor function and durability. We report the results of a Phase 1/2 study in patients with relapsed or refractory large B-cell lymphoma (LBCL). In Phase 2, 79 patients received Anbal-cel, and efficacy was evaluated in 73 patients. The complete response (CR) and partial response (PR) rates were 67.1% and 8.2%, respectively. Median progression-free survival (PFS) was 6.04 months (95% CI, 4.34-16.46), and the 6-, 12-, and 18-month PFS rates were 50.9%, 41.1%, and 35.2%, respectively. Median overall survival (OS) was not reached, with 12- and 18-month OS rates of 66.6% and 57.3%. CAR T-cell expansion was significantly greater in responders than in non-responders (median Cmax: 20,403 vs. 8,580 copies/μg). Patients were categorized into long-term response (LR) group or non-LR group based on sustained CR at 6 months. Reduced PD-1 and TIGIT expression on CAR-positive T cells was observed in LR group. Most patients (97.5%) experienced grade ≥3 adverse events, most commonly neutropenia (93.7%), followed by thrombocytopenia (41.8%) and anemia (30.4%). Cytokine release syndrome and neurologic events occurred in 57.0% and 13.9% of patients, respectively. Grade 3 CRS occurred in 8.9% of patients, with no grade 4 events reported, and grade ≥3 neurologic events occurred in 3.8%. Serious infections occurred in 25.3% of patients, and grade 5 infection was reported in 3 patients. This trial was registered at Clinicaltrials.gov (NCT04836507).