PS945 KTE-X19, AN ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR T CELL THERAPY, IN ADULT PATIENTS WITH RELAPSED/REFRACTORY ACUTE LYMPHOBLASTIC LEUKEMIA: END OF PHASE 1 RESULTS OF ZUMA-3
Authors: B.D. Shah, M.R. Bishop, O.O. Oluwole, A.C. Logan, M.R. Baer, W.B. Donnellan, K.M. O’Dwyer, H. Holmes, M.L. Arellano, A. Ghobadi, J.M. Pagel, Y. Lin, R.D. Cassaday, J.H. Park, A. Mardiros, T. Shen, L. Goyal, R. Vezan, R.K. Jain, W.G. Wierda
Journal: HemaSphere (2019)

Background: Standard therapy for adult patients with high-risk acute lymphoblastic leukemia (ALL) is allogeneic-hematopoietic cell transplantation (HCT) from a matched-sibling (MSD) or matched unrelated donor (MUD). When the conventional donor is not available, HCT from a partially-mismatched unrelated donor (MMUD), cord blood transplantation (CBT), or familial haploidentical mismatched transplantation (FMMT) are considered Aims: We analyzed long-term HCT outcomes according to the donor types including MMUD-HCT and double-CBT (DCBT) as an alternative choice compared to the conventional donor transplantation. Methods: We initially enrolled 440 adult ALL patients who underwent transplantation from 2005 to 2015 in their first remission (CR1). Before 2010, our post-remission strategy for high-risk ALL was to offer allogeneic-HCT according to the donor availability (MSD or MUD) and sometimes used MMUD for next step. After 2010, DCBT was mainly used as an alternative choice. Conditioning regimen for DCBT was TBI, ARA-C and fludarabine. Graft-versus-host disease (GVHD) prophylaxis was attempted by administering calcineurin inhibitors (cyclosporine for MSD, tacrolimus for others) plus methotrexate. Antithymocyte globulin (ATG) was administered to the patients who received grafts from MMUD. Results: Engraftment was successful in all donor types, but neutrophil and platelet recovery was significantly delayed only after DCBT (median recovery for neutrophil and platelet was 25 and 33.5 days respectively). After median follow-up of 58.1 months (range, 6.5–145.7), 5-year OS for the entire 440 patients was 58.3%. In detail, 5-year OS for MSD, MUD, MMUD, and DCBT was 60.1%, 57.2%, 62.9%, and 65.1% (p = 0.918). DCBT showed significantly higher NRM rate (29.6%) and lower relapse rate (7.2%). Interestingly, calculated GVHD and relapse-free survival (GRFS) for MSD, MUD, MMUD, and DCBT was 33.1%, 14.5%, 42.1%, and 50.3% (p = 0.001), respectively, which was related with higher incidence of severe chronic GVHD in MUD (30.1%) and MSD (14.8%) compared to DCBT (4.2%, p < 0.001). In high-risk subgroup (n = 379) including 200 Philadelphia chromosome (Ph)-positive ALL, 5-year OS for MSD, MUD, MMUD, and DCBT was 57.9%, 58.5%, 59.2%, and 60.7%, but the 5-year GRFS was 29.7%, 14.0%, 36.5%, and 47.7%, respectively, which was related with lower relapse rate (8.7%) and low severe chronic GVHD (2.6%) of DCBT subgroup. Multivariate analysis showed that younger age <40 yrs and mild to moderate chronic GVHD was related with favorable OS and GRFS, while MUD-HCT and severe chronic GVHD were related with poor GRFS. Summary/Conclusion: Our data showed similar transplant outcomes of alternative donors such as DCBT and ATG-applied MMUD compared to conventional donor transplants in ALL patients in CR1. In addition, GRFS was rather superior in patients treated with DCBT. Our long-term outcome results revealed that DCBT might be a good alternative choice for patients who are not available with conventional allogeneic donors.