Retrospective multicentric comparison of out-ofspecification and standard-of-care tisagenlecleucel infusion for diffuse large b-cell lymphoma

Abstract Tisagenlecleucel (Tisa-cel) is an autologous anti-CD19 CAR T-cell that requires a complex manufacturing process. A product with all the quality criteria is acknowledged as “standard-of-care” (SOC), while the ones not fitting the benchmark are considered “out-of-specification” (OOS). This retrospective multicentric study compares the efficacy and safety outcomes of OOS Tisa-cel and SOC products. We enrolled a total of 44 DLBCL patients who underwent the treatment according to Italian Medicines Agency criteria. Among them, 11 received OOS Tisa-cel. After a median follow-up of 19.1 months (range, 0.7–43.9), one-year PFS was 45.5% and 36.4% (p = 0.899) and one-year OS was 47.7% and 55.7% (p = 0.598) for OOS and SOC patients, respectively. CRS occurred in 63.6% of patents in the OOS group vs 81.2% in the SOC group (p = 0.248), grade > 2 CRS in 0% vs 3% (p = 1) and ICANS in 3% vs 9% (p = 0.451), respectively. No patients developed grade > 2 ICANS. No cases of non-relapse mortality have been reported. Our data show that OOS infusion does not increase toxicity and has comparable outcomes to SOC products, suggesting to pursue this option in the absence of therapeutic alternatives. However, larger studies of OOS criteria effect on clinical outcomes are needed.