Anbalcabtagene autoleucel (PD-1 and TIGIT knockdown CD19 CAR T-cell therapy) for relapsed or refractory LBCL: the...

Anbalcabtagene autoleucel (anbal-cel) is a CD19-directed chimeric antigen receptor (CAR) T-cell therapy incorporating dual PD-1 and TIGIT knockdown to enhance antitumor function and durability. We report results from a phase 1 and 2 study in patients with relapsed or refractory large B-cell lymphoma. In phase 2, 79 patients received anbal-cel, and its efficacy was evaluated in 73 patients. The complete response (CR) and partial response rates were 67.1% and 8.2%, respectively. Median progression-free survival (PFS) was 6.04 months (95% confidence interval, 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%, respectively. CAR T-cell expansion (Cmax) was significantly greater in responders than in nonresponders (median Cmax, 20 403 vs 8580 copies per 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+ T cells was observed in the 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 (CRS) and neurological 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 neurological events occurred in 3.8% of patients. Serious infections occurred in 25.3% of patients, including grade 5 infection reported in 3 patients. This trial was registered at www.clinicaltrials.gov as #NCT04836507.