急性 B 淋巴细胞白血病中第二次抗 CD19 CAR-T 细胞治疗 (CAR-T2) 的结局及异基因造血干细胞移植对疗效的影响

For patients exhibiting a suboptimal response to the first chimeric antigen receptor (CAR) T-cell therapy (CART1) or relapse after remission, secondary CAR T-cell therapy (CART2) for the same target may be an option.

We retrospectively analyzed patients with acute B-cell lymphoblastic leukemia (B-ALL) receiving CD19 CART1 at our center (n = 84) to report the clinical outcomes of CART2 and to identify the factors that may influence the outcomes. Twenty-six patients received CART2 for suboptimal response or relapse post-CART1. The incidence of cytokine release syndrome (CRS) after CART2 was 65. 4% (17/26), with 11 cases classified as grade 1 (42. 3%), four cases as grade 2 (15. 4%), and two cases as grade 3 (7. 7%). Neurotoxicity was observed in one patient (3. 8%) after CART2 infusion. Fourteen patients (53. 8%) achieved complete remission (CR) after CART2. CART2 exhibited an inferior response rate (CART2: 53. 8%, 14/26; CART1: 81. 0%, 64/79; P = 0. 006) and a lower incidence of severe CRS (CART2: 7. 7%, 2/26; CART1: 30. 4%, 24/79; P = 0. 020) compared with CART1, with a median progression-free survival (PFS) and a median overall survival (OS) of 6.

2 months and 11. 2 months, respectively. In particular, patients who progressed after consolidative allogeneic hematopoietic stem cell transplantation (allo-HSCT) following CART1 and then received CART2 demonstrated promising outcomes with a response rate of 80. 0% (8/10), a median PFS of 7. 9 months, and a median OS of 25. 1 months. After adjusting for the confounding factors, the response rate (85.

7%, 6/7) of CART2 administered to this cohort was better than those who did not bridge to allo-HSCT receiving CART2 (28. 6%, 2/7) or non-CART2 treatments (13. 3%, 2/15). The median OS after CART2, which was not reached, was significantly better than the median OS after CART2 (3. 9 months, P = 0. 014) and non-CART2 treatments (6. 0 months, P = 0. 012) administered in patients who did not undergo consolidative allo-HSCT post-CART1.

Our results indicated that, although less effective than CART1, a subset of patients can still benefit from CART2 with mild adverse effects. For patients who relapsed after consolidative allo-HSCT post-CART1, treatment with CART2 is a viable option.