CAR T‑Cell Therapy as a Bridging Strategy to Second Transplant in Relapsed B‑Cell ALL

A second allogeneic transplant (HSCT2) may offer cure for selected patients with acute lymphoblastic leukemia (ALL) relapsing after first transplant (HSCT1), however, outcomes have historically been poor, largely driven by high incidence of subsequent relapse. Chimeric antigen receptor (CAR) T‑cell therapy induces deep and durable remissions in relapsed/refractory (R/R) ALL, yet its role as a bridge to HSCT2 remains under studied. Consolidation with transplant after CAR-T therapy may enhance post‑HSCT2 disease control and improve outcomes.

To compare HSCT2 outcomes according to bridging therapy strategies, with a particular focus on CAR T‑cell therapy versus non‑CAR bridging approaches.

This is a single‑center retrospective analysis of adult patients with relapsed B‑cell ALL after a HSCT1 who subsequently underwent a HSCT2 in complete remission (CR) at City of Hope.

Among 55 adults with relapsed B‑ALL who underwent HSCT2, the median age was 32, with a median of 4 prior lines of therapies. The median time from HSCT1 to relapse was 425 days, and over half of patients proceeded to HSCT2 in ≥CR3. Salvage therapy included CAR T‑cell therapy in 23 patients (42%), blinatumomab in 12 (22%), inotuzumab ozogamicin in 12 (22%), and other regimens in 8 (15%). Baseline patients and disease characteristics were not significantly different between those receiving CAR T and other salvage approaches. Patients receiving CAR T-cell therapy before HSCT2 had significantly improved 2-year progression free survival (PFS) (67.6% vs. 31.4%, p= 0.003) and overall survival (OS) (77.3% vs. 51.6%, p= 0.021) compared with other salvage therapies, respectively. Cumulative incidence of relapse was significantly lower in patients who received CAR T‑cell therapy before HSCT2 (p=0.01), while non-relapse mortality was similar between the two groups (p=0.43). In multivariable analysis, CAR T-cell therapy remained independently associated with superior PFS (HR 0.26; 95% CI, 0.10-0.62; p < 0.001) and OS (HR 0.33; 95% CI, 0.13-0.81; p = 0.026). A longer interval from HSCT1 to relapse (>475 days) also predicted improved OS (HR 0.42; 95% CI, 0.18-0.96; p = 0.04), while older age showed a trend toward inferior OS (HR 2.17; 95% CI, 0.97-4.89; p = 0.054).

Our study supports CAR T-cell therapy as an effective bridging strategy to HSCT2 in selected patients with relapsed B-ALL, associated with improved post HSCT2 survival outcomes and reducing relapse. Careful optimization of patient selection and timing of transplant remains critical to maximize long-term outcomes.