Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis Attenuates Disparity in Outcomes Between Use of Matched or Mismatched Unrelated Donors

Abstract

PURPOSEAccess to allogeneic hematopoietic cell transplantation (HCT) remains limited among persons of non-European ancestry if human leukocyte antigen (HLA) matching is required. We evaluated whether post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis improved HCT outcomes with HLA-matched unrelated donor (MUD) and mismatched unrelated donor (MMUD) HCT when compared with calcineurin inhibitor (CNI)-based prophylaxis.METHODSThree-year overall survival (OS) and GVHD-free, relapse-free survival (GRFS) were compared between adult recipients undergoing initial MUD or single HLA locus MMUD HCT with either PTCy- or CNI-based prophylaxis who were reported to the Center for International Blood and Marrow Transplant Research between 2017 and 2021.RESULTSIncluded were 10,025 HCT recipients (7,272 recipients of MUD with CNI, 1,681 MUD with PTCy, 613 MMUD with CNI, and 459 MMUD with PTCy) who underwent HCT for acute leukemia (70.9%) or myelodysplastic syndromes (29.2%). Median patient age was 60.7 years (range, 18.0-82.7) and median follow-up was 36.6 (range, 3.0-77.8) months. When compared with MUD HCT with PTCy, MMUD HCT with PTCy had similar OS (hazard ratio [HR], 0.96 [95% CI, 0.823 to 1.11]; P = .60) and GRFS (HR, 0.90 [0.79 to 1.02]; P = .1). When compared with MUD HCT with CNI, OS was improved after MUD HCT with PTCy (HR, 0.88 [0.80 to 0.96]; P = .004) and GRFS was improved with PTCy after either MUD (HR, 0.61 [0.57 to 0.66]; P < .0001) or MMUD (HR, 0.68 [0.60 to 0.76]; P < .0001) HCT. Benefit from PTCy was independent of patient ancestry. Global registry level analysis demonstrated that inclusion of MMUD increased donor availability regardless of recipient ancestry.CONCLUSIONUse of PTCy results in comparable OS and GRFS using either MUD or MMUD HCT, expanding access to HCT for patients from all racial and ethnic ancestry groups.

FIG 1.

Adjusted Kaplan-Meier estimates of GRFS and OS in recipients of (A) PTCy and (B) CNI. CNI, calcineurin inhibitor; GRFS, graft-versus-host disease-free, relapse-free survival; HLA, human leukocyte antigen; OS, overall survival; PTCy, post-transplant cyclophosphamide; URD, unrelated donor.

FIG 2.

Cumulative incidence of (A) acute GVHD grades 2-4, (B) acute GVHD grades 3-4, and (C) moderate/severe chronic GVHD on the basis of the GVHD prophylaxis approach and donor/recipient HLA matching group. CNI, calcineurin inhibitor; GVHD, graft-versus-host disease; HLA, human leukocyte antigen; PTCy, post-transplant cyclophosphamide; URD, unrelated donor.

FIG 3.

Cumulative incidence of (A) relapse and (B) nonrelapse mortality; and (C) relative causes of death in each donor/GVHD prophylaxis group. CNI, calcineurin inhibitor; GVHD, graft-versus-host disease; PTCy, post-transplant cyclophosphamide; URD, unrelated donor.

FIG 4.

Forest plot results of the multivariable adjusted risk of primary and secondary end points compared with recipients of MUD HCT using CNI-based GVHD prophylaxis. CNI, calcineurin inhibitor; GVHD, graft-versus-host disease; HCT, hematopoietic cell transplantation; HR, hazard ratio; MMUD, mismatched unrelated donor; MUD, matched unrelated donor; PTCy, post-transplant cyclophosphamide.

FIG 5.

Registry-level modeling using results from 50,000 preliminary unrelated donor searches. Donors age 35 years and younger with at least a 75% probability of HLA matching at the designated degree were considered. (A) The probability of at least one available donor existing on the basis of patient ancestry improves in all groups (global P < .001) if both MUD and MMUD are considered, and (B) the median number of existing donors in patients who had at least one available donor if only MUDs are considered versus MUDs and MMUDs are considered as suitable. AFA, African American; API, Asian/Pacific Islander; HIS, Hispanic/White; HLA, human leukocyte antigen; MMUD, mismatched unrelated donor; MUD, matched unrelated donor; NAM, Native American; NHW, non-Hispanic/White; URD, unrelated donor.