Post-Transplant Cyclophosphamide Eliminates Disparity in GvHD-Free, Relapse-Free Survival and Overall Survival between 8/8 Matched and 7/8 Mismatched Unrelated Donor Hematopoietic Cell Transplantation in Adults with Acute Leukemia or MDS

Background Post-transplant cyclophosphamide (PTCy) has become a standard of care for graft-versus-host disease (GvHD) prophylaxis in recipients of HLA matched and mismatched unrelated donor (URD) allografts, enabling successful hematopoietic cell transplantation (HCT) regardless of patient ancestry. We aimed to determine differences in overall survival (OS) and GvHD-free, relapse-free survival (GRFS) between 8/8 and 7/8 URD allografts using PTCy and calcineurin-inhibitor (CNI)-based approaches and measure the impact of PTCy on any remaining outcome differences due to HLA disparity. Methods The primary objective was to compare GRFS and OS between 8/8 and 7/8 URD HCT with PTCy using the CIBMTR database. Secondary objectives were to compare GRFS, OS, and other clinical outcomes among 8/8 and 7/8 URD recipients using PTCy or CNI-based prophylaxis. The study included adult patients (age≥18y) undergoing first URD HCT for ALL, AML, MDS between 1/2017-6/2021. Recipients of abatacept were excluded. Kaplan-Meier curves were used to estimate probability of GRFS and OS. Cox regression examined the independent effect of HLA match and GVHD prophylaxis controlling for other clinical factors on outcomes referenced to 8/8 URD HCT using CNI. Results Figure 1 shows demographics for the 4 patient cohorts identified by HLA match and GvHD prophylaxis: 8/8 CNI (N=7272), 7/8 CNI (N=459), 8/8 PTCy (N=1681), and 7/8 PTCy (N=613). 8/8 URD recipients were predominately White/non-Hispanic and CNI recipients and were more likely to receive myeloablative conditioning and be transplanted in earlier years. Otherwise patient characteristics were similar.Multivariable regression analysis showed no significant differences in GRFS between recipients of 8/8 and 7/8 URD PTCy HCT at 1, 2 and 3-years post-HCT; GRFS in both were significantly better when compared to 8/8 and 7/8 CNI (Figure 2). GRFS was not significantly different between 8/8 and 7/8 CNI (p=0.2069). OS was similar between 8/8 PTCy, 7/8 PTCy, and 8/8 CNI, and all were significantly superior to 7/8 CNI (Figure 3). Differences between outcomes by GvHD prophylaxis types appeared to be driven by significantly higher NRM (p<0.001), grade 3-4 aGVHD (p<0.001), and moderate/severe chronic GvHD (p<0.001] in CNI groups (Figure 3). Conclusions Use of PTCy-based GvHD prophylaxis has resolved previously observed differences in GRFS and OS between 8/8 and 7/8 URD HCT. Furthermore, PTCy-based regimens are associated with superior outcomes in 8/8 and 7/8 URD transplant compared with CNI-based regimens. HCT using an 8/8 URD PTCy, if available, continues to be the best option for patients lacking a matched sibling donor, but 7/8 URD PTCy appears to be a suitable alternative. HLA mismatched donor sources substantially increase access to HCT for patients, regardless of their ancestry.