TY - JOUR
T1 - A Multicenter Phase 2 Clinical Trial of 10-Day Decitabine, Dose-Escalated Donor Lymphocyte Infusion, and Ruxolitinib for Relapsed Acute Myeloid Leukemia and Myelodysplastic Syndromes after Allogeneic Hematopoietic Cell Transplantation
AU - Rashidi, Armin
AU - Huselton, Eric J.
AU - Stefanski, Heather E.
AU - DeFor, Todd E.
AU - Shanley, Ryan
AU - Choi, Jaebok
AU - DiPersio, John F.
AU - Juckett, Mark
AU - Miller, Jeffrey S.
AU - Weisdorf, Daniel J.
AU - Schroeder, Mark A.
N1 - Publisher Copyright:
© 2023 The American Society for Transplantation and Cellular Therapy
PY - 2023/5
Y1 - 2023/5
N2 - Post-transplantation relapse of acute myeloid leukemia and myelodysplastic syndromes has a poor prognosis. Donor lymphocyte infusion (DLI) is one treatment approach. However, efficacy is limited, and toxicity, mostly in the form of acute graft-versus-host disease (GVHD), is frequent. We tested a novel approach using 10-day decitabine, dose-escalated DLI, and ruxolitinib in a multicenter phase 2 trial aimed at increasing the efficacy of DLI and reducing its toxicity. Up to four 28-day cycles were administered. The primary endpoint was 6-month overall survival (OS). Of the 14 patients who started cycle 1, 13 received 1 DLI, 6 received 2 DLIs, and 1 received 3 4 DLIs. A preplanned interim analysis after enrolling 14 patients suggested futility, and the trial was closed to accrual. The final analysis showed a 6-month OS of 36% (95% confidence interval [CI], 18 to 72), a 1-year progression-free survival of 7% (95% CI, 1% to 47%), a 6-month cumulative incidence of grade II-IV acute GVHD of 57% (95% CI, 26% to 80%), and a 1-year nonrelapse mortality of 14% (95% CI, 2% to 38%). The combined modality treatment studied in this trial was ineffective and did not reduce DLI toxicity.
AB - Post-transplantation relapse of acute myeloid leukemia and myelodysplastic syndromes has a poor prognosis. Donor lymphocyte infusion (DLI) is one treatment approach. However, efficacy is limited, and toxicity, mostly in the form of acute graft-versus-host disease (GVHD), is frequent. We tested a novel approach using 10-day decitabine, dose-escalated DLI, and ruxolitinib in a multicenter phase 2 trial aimed at increasing the efficacy of DLI and reducing its toxicity. Up to four 28-day cycles were administered. The primary endpoint was 6-month overall survival (OS). Of the 14 patients who started cycle 1, 13 received 1 DLI, 6 received 2 DLIs, and 1 received 3 4 DLIs. A preplanned interim analysis after enrolling 14 patients suggested futility, and the trial was closed to accrual. The final analysis showed a 6-month OS of 36% (95% confidence interval [CI], 18 to 72), a 1-year progression-free survival of 7% (95% CI, 1% to 47%), a 6-month cumulative incidence of grade II-IV acute GVHD of 57% (95% CI, 26% to 80%), and a 1-year nonrelapse mortality of 14% (95% CI, 2% to 38%). The combined modality treatment studied in this trial was ineffective and did not reduce DLI toxicity.
KW - Acute myeloid leukemia
KW - Decitabine
KW - Donor lymphocyte infusion
KW - Hematopoietic cell transplantation
KW - Myelodysplastic syndromes
KW - Ruxolitinib
UR - http://www.scopus.com/inward/record.url?scp=85150791701&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2023.02.010
DO - 10.1016/j.jtct.2023.02.010
M3 - Article
C2 - 36804933
AN - SCOPUS:85150791701
SN - 2666-6367
VL - 29
SP - 328.e1-328.e6
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 5
ER -