Superiority in the Longer Duration of Response and Better Central Nervous System Penetration of CAR-T Cell Therapy over Blinatumomab Infusion for Relapsed/ Refractory B-Cell Acute Lymphoblastic Leukemia: A Retrospective Single-Center Analysis

Introduction Chimeric antigen receptor T-cell (CAR-T) infusion (Am J Hematol, 2021; Blood, 2022) and bispecific T-cell engager (BiTE) antibody therapy (such as blinatumomab) (Ann Med, 2023; J Clin Oncol, 2023) have emerged as the most promising immuno-therapy for relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) patients. Herein, we retrospectively compared these two regimens on the safety and efficacy in treating r/r B-ALL patients. Aim To analyze the overall response rate (ORR), duration of response (DOR), Central Nervous System (CNS) involvement and adverse events (AEs) with CAR-T therapy compared with blinatumomab infusion for r/r B-ALL. Method In this study, a total of 137 r/r B-ALL patients treated with at least one dose of blinatumomab (B-group, n=50) or CAR-T cell therapies (C-group, n=87) between January 2018 and March 2024 were retrospectively analyzed. Results Significant differences were identified in the baseline characteristics of two groups. The C-group with a lower median age (29 vs. 40yrs, P<0.001) underwent a higher rate both of prior treatment lines≥3 (66% vs. 34%, P<0.001) and extramedullary relapse (18% vs. 0%, P<0.001). The overall response rate (ORR) at the day30 and 6-month assessment showed no significantly differences between the two groups, respectively (90% vs. 80%, P=0.114; 76% vs. 57%, P=0.058). Whereas the patients in the C-group achieved a higher ORR in the 3-month evaluation (87% vs. 65%, P=0.009). The median follow-up time in C- and B-groups was 184 days (range, 8-2272 days) and 181 days (range, 11-821 days) respectively. The 6-month DOR of the patients in the C-group was significantly higher than that of patients in the B-group (89% vs. 72.6%, P=0.0062). In prespecified subgroup analysis, only history of transplantation was analyzed as a negative factor of the 6-month DOR in the B-group (HR 7.24; 95% CI, 7.17 to 45.05; P=0.03). Remarkably, four patients without previous history of CNS leukemia further progressed with it in B-group. They subsequently received CAR-T cell therapy as a salvage treatment and maintained sustained remission during the follow-up period. In the C-group, 6 of 8 patients with CNS leukemia achieved sustained remission during the follow-up period, while the other two experienced a CNS relapse after CR1. However, the C-group showed a higher incidence of cytokine release syndrome (CRS) of grade ≥ 3 (22% vs. 4%, P=0.013) and neurological toxicity (11% vs. 0%, P<0.001), as well as a more severe toxicity of blood (anemia of grade ≥ 3, 60% vs. 36%, P=0.007; neutropenia of grade ≥ 3, 98% vs. 58%, P<0.001; thrombocytopenia of grade ≥ 3, 67% vs. 38%, P<0.001). Conclusion: There a quicker response occurs in the early 3 months with CAR T-cell therapy in treating r/r B-ALL. Ever though there are more severe adverse events, it cannot conceal the superiority in the longer DOR and better CNS penetration with CAR-T cell therapy over the blinatumomab infusion. Our results further demonstrate that it is imperative to standardize the full process management of CAR T-cell therapy and research novel strategies to mitigate sever toxicities.