S240: CD7 CHIMERIC ANTIGEN RECEPTOR T CELLS BRIDGING TO ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IMPROVED DISEASE-FREE SURVIVAL IN REFRACTORY/RELAPSED T-CELL ACUTE LYMPHOBLASTIC LEUKEMIA

Abstract

Background: Our previous clinical study has shown that the patients with refractory/relapsed T-cell acute lymphoblastic leukemia (r/r T-ALL) have achieved 90% complete remission (CR) with donor-derived CD7 chimeric antigen receptor T cells (CART), but some cases have developed donor-recipient mixed chimerism and remarkable pancytopenia (Pan J. et al. JCO 2021). It is crucial to quickly bridge to allogeneic hematopoietic stem cell transplantation (allo-HSCT) for hematopoietic reconstitution. Aims: In current study, the safety and efficacy of allo-HSCT in r/r T-ALL after CD7-CART are investigated. Methods: From February 2018 to December 2021, total 57 patients with r/r T-ALL who underwent allo-HSCT in our hospital were included. The median age was 13(4-69) years old. Extramedullary disease (EMD) was found in 32 patients (56.1%). Somatic gene mutations (NOTCH 18, IL7R 3, JAK 2, FBXW7 2, WT1 2, NRAS 2) were detected in 17 patients. Eighteen patients who were resistant to chemotherapy received CD7-CART (CART group) before transplant, and all patients except one achieved CR. Thirty-nine r/r T-ALL patients were managed with chemotherapy before transplant (non-CART group), and 25 patients achieved CR (CR arm), 14 patients were in non-remission (NR) (NR arm) before transplantation. Conditioning regimens in CART group were either busulfan/fludarabine (n=12) or TBI/fludarabine (n=6). Conditioning regimens in non-CART group were either busulfan/fludarabine (n=11) or TBI/ fludarabine (n=28). ATG was used for haploidentical or unrelated transplants. Cyclosporine, mycophenolate mofetil and short-term methotrexate were employed for GVHD prophylaxis. Results: In CART group, the median time of neutrophils and platelets engraftment were 15 (10-22) and 18 (8-50) days. With the median follow-up 283 (14-496) days, 13 patients survived and 5 patients died (infection 4, cerebral hemorrhage 1). Three of 18 (16.7%) patients relapsed (CD7- 1, CD7 + 2) after transplantation and have been receiving treatment so far. One-year overall survival (OS) and disease-free survival (DFS) were 77.8% and 61.2%. Transplantation-related mortality (TRM) was 16.6%. In non-CART group, the median time of neutrophils and platelets engraftment were 15 (10-22) and 15 (8-28) days. Total 25 patients survived and 14 cases died (relapse 3, infection 4, GVHD 1, multiple organ failure 6). Fifteen of 39 (38.5%) patients relapsed. In CR arm, with the median follow-up 637(9-1357) days, one-year OS and DFS were 71.0% and 59.2%. In NR arm, with the median follow-up 517 (7-513) days, one-year OS and DFS were 59.2% and 40%. TRM was 28.2%. Summary/Conclusion: Donor-derived CD7-CART followed by allo-HSCT has achieved similar survival (OS, DFS) and lower relapse rate and TRM compared with chemotherapy followed by allo-HSCT in r/r T-ALL. CD7-CART may result in better disease control which will translate into less disease recurrence after transplant.