复发/难治性 B-ALL 成人对 CD19 CAR-T 细胞治疗应答后首次和第二次异基因移植巩固治疗

CD19-targeted chimeric antigen receptor T cell (CAR-T) therapy has led to unprecedented rates of complete remission (CR) in children and adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), yet the majority of adults relapse after initial response. One proposed method to extend the durability of remission in adults following response to CAR-T therapy is consolidation with allogeneic hematopoietic cell transplantation (alloHCT).

Considering the limited published data for the utility of post CAR-T therapy consolidative alloHCT in r/r B-ALL, especially data related to patients receiving a second alloHCT, we sought to describe outcomes of patients with r/r B-ALL at our institution who received their first or second alloHCT following response to CAR-T therapy.

We performed a retrospective analysis of adult patients with r/r B-ALL who responded to either investigational or standard of care (SOC) CD19-targeted CAR-T therapy and underwent consolidation with alloHCT while in CR without interim therapy.

We identified 45 patients, of whom 26 (58%) and 19 (42%) received their first and second alloHCT as consolidation post CAR-T therapy, respectively. The median age was 31 years (range: 19-67) and 31 (69%) patients were Hispanic. Ph-like was the most common genetic subtype and comprised over half of cases (53%; n = 24). The median number of prior therapies pre-transplant was 5 (range: 2-7), and disease status at the time of alloHCT was CR1, CR2 or CR3 in 7 (16%), 22 (49%) and 16 (35%) patients, respectively. The median time from CAR-T therapy until alloHCT was 93 (range: 42-262) days. The conditioning regimen was radiation-based myeloablative (MAC) in 22 (49%) patients. With a median follow-up of 2. 47 years (range: 0. 13-6.

93), 2-year overall survival (OS), relapse free survival (RFS), cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) were 57. 3% (95% CI: 0. 432-0. 760), 56. 2% (95% CI: 0. 562-0. 745), 23. 3% (95% CI: 0. 13-0. 42), and 20. 4% (95% CI: 0. 109-0. 384), respectively. Two-year OS (52% vs. 68%, P = . 641), RFS (54% vs. 59%, P = . 820), CIR (33. 5% vs. 8. 5%, P = . 104), and NRM (12. 5% vs. 32. 2%, P = .

120) were not significantly different between patients who underwent their first vs. second transplant, respectively. In univariate analysis, only Ph-like genotype was associated with inferior RFS (P = . 03). AlloHCT post CAR-T response is associated with a relatively low early mortality rate and encouraging survival results in high-risk adults with r/r B-ALL, extending to the second alloHCT for fit and eligible patients.