Long-Term Outcomes of Second Allogeneic Transplantation Following CD7 CAR-T in Remission for T-Cell Acute Lymphoblastic Leukemia or Lymphoma.

Patients with T-cell acute lymphoblastic leukemia or lymphoma (T-ALL/LBL) who relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) face limited treatment options and a poor prognosis. While CD7-targeted chimeric antigen receptor T-cell (CAR-T) therapy has demonstrated high remission rates in T-ALL/LBL, its safety and efficacy in post-transplant relapse remain underexplored in patients who experience post-transplant relapse and subsequently undergo a second transplant after CAR-T treatment. Here, we report the efficacy and safety of CD7 CAR-T in T-ALL/LBL patients who relapsed post-transplant from the phase I/II clinical trials (https://clinicaltrials.gov/ NCT04572308 and NCT04916860), and provide the first comprehensive analysis of long-term outcomes following a second allo-HSCT after CD7 CAR-T treatment. To analyze the prognosis of second transplant post-CD7 CAR-T and safety of CD7 CAR-T in T-ALL/LBL patients who relapsed post-transplant. This study included 24 patients (21 T-ALL, 3 T-LBL) who relapsed after first allo-HSCT and received naturally selected CD7 CAR-T (NS7CAR-T) therapy from patient-derived (n = 18) or prior transplant donor-derived (n = 6) at our center. Patients either proceeded to a second allo-HSCT or not. We analyzed NS7CAR-T efficacy and safety, survival, relapse, and transplant-related complications following second transplant. After NS7CAR-T, 21/23 (91.3%) achieved minimal residual disease (MRD)-negative CR in bone marrow (BM). For the 13 patients with extramedullary disease (EMD), 8 (61.5%) achieved CR. Following NS7CAR-T, 18 patients proceeded to a second allo-HSCT, while the remaining 6 did not. Prior to second transplant, all patients were MRD-negative in BM but one had persistent EMD. The median follow-up after second transplant was 510 days (range: 32 to 1352). For the 18 patients, the 3-year overall survival (OS) was 46.4%, and the 3-year leukemia-free survival (LFS) was 44.4%. The 3-year cumulative incidence of relapse was 16.7%, and the 3-year nonrelapse mortality (NRM) was 48.0%. In contrast, all 6 patients who did not undergo a second transplant died, with a median survival of 102 days post-CAR-T infusion. NS7CAR-T therapy showed a high CR rate for T-ALL/LBL patients who relapsed post-transplant. Consolidation with a second transplant appears feasible and may offer a promising therapeutic strategy for these heavily pretreated patients. However, the high NRM demonstrated the need for further efforts to mitigate this risk. Patients who did not receive consolidative transplantation experienced uniformly poor outcomes.