CAR-T 细胞用于 CAR-T 治疗失败后的挽救治疗

Outcomes for post-chimeric antigen receptor (CAR) T cell therapy (CART) relapse are poor. The utilization of a unique CAR T cell construct for post-CART failure is increasing, but this approach is not well described. In this study, with CART-A the first unique CAR T cell construct received and CART-B the second, the primary objective was to characterize outcomes following CART-B. Secondary objectives included evaluating safety and toxicity with sequential CART infusions; investigating the impact of potential factors, such as antigen modulation and interval therapy, on CART-B response; and characterizing long-term outcomes in patients receiving multiple CARTs. This was a retrospective review (NCT03827343) of children and young adults with B cell acute lymphoblastic leukemia (B-ALL) undergoing CART therapy who received at least 2 unique CART constructs, excluding interim CART reinfusions of the same product. Of 135 patients, 61 (45. 1%) received 2 unique CART constructs, including 13 who received >2 CARTs over time. Patients included in this analysis received 14 distinct CARTs targeting CD19 and/or CD22. The median age at CART-A was 12. 6 years (range, 3.

3 to 30. 4 years). The median time from CART-A to CART-B was 302 days (range, 53 to 1183 days). CART-B targeted a different antigen than CART-A in 48 patients (78. 7%), owing primarily to loss of CART-A antigen target. The rate of complete remission (CR) was lower with CART-B (65. 5%; 40 of 61) than with CART-A (88. 5%; 54 of 61; P = . 0043); 35 of 40 (87. 5%) CART-B responders had CART-B targeting a different antigen than CART-A. Among the 21 patients with a partial response or nonresponse to CART-B, 8 (38. 1%) received CART-B with the same antigen target as CART-A.

Of 40 patients with CART-B complete response (CR), 29 (72. 5%) relapsed. For the 21 patients with evaluable data, the relapse immunophenotype was antigen negative in 3 (14. 3%), antigen dim in 7 (33. 3%), antigen positive in 10 (47. 6%), and lineage switch in 1 (4. 8%).

The median relapse-free survival following CART-B CR was 9. 4 months (95% confidence interval [CI], 6. 1 to 13. 2 months), and overall survival was 15. 0 months (95% CI, 13. 0 to 22. 7 months). Given the limited salvage options for post-CART relapse, identifying optimizing strategies for CART-B is critical.

We raise awareness about the emerging use of CART for post-CART failure and highlight clinical implications accompanying this paradigm shift.