Post-Transplant Cyclophosphamide-Based Graft-Versus-Host Disease Prophylaxis After Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation

Abstract

Purpose: Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for advanced hematologic malignancies. HSCT using human leukocyte antigen (HLA)-mismatched donors is historically associated with inferior survival. Patients from underrepresented racial and ethnic groups more frequently rely on HLA-mismatched donors. We hypothesized that post-transplant cyclophosphamide (PTCy) based graft versus host disease (GVHD) prophylaxis would improve outcomes for HSCT recipients using peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors (MMUDs) by reducing the risk of GVHD.

Methods: This phase II, nonrandomized, multicenter trial assessed PBSCs in the setting of a GVHD prophylaxis regimen of cyclophosphamide, tacrolimus, and mycophenolate mofetil in two adult strata: myeloablative conditioning (MAC) and reduced-intensity or nonmyeloablative (RIC/NMA) conditioning before HSCT from a MMUD. The primary objective was to estimate 1 year overall survival (OS) for each stratum. Key secondary end points included incidences of acute and chronic GVHD.

Results: A total of 145 patients enrolled, with 59% self-identifying within an underrepresented group. The 1 year OS was 83.8% (95% CI, 73.1% to 90.4%) for MAC and 78.6% (95% CI, 67% to 86.5%) for RIC/NMA. Incidences of grades III to IV acute GVHD at 6 months were 8% (95% CI, 3.2 to 15.6) for MAC and 10% (95% CI, 4.4 to 18.4) for RIC/NMA. Moderate/severe chronic GVHD at 1 year was 10.3% (95% CI, 4.4 to 18.9) for MAC and 8.6% (95% CI, 3.5 to 16.6) for RIC/NMA. 32% of patients whose donors matched at fewer than seven of eight HLA alleles had similar OS compared with those with donor matched at seven of eight alleles.

Conclusion: PTCy-based GVHD prophylaxis after MMUD HSCT with PBSC grafts results in favorable 1 year OS. Using MMUDs expands donor availability to all patients regardless of ancestry (ACCESS; ClinicalTrials.gov identifier: NCT04904588).

FIG 1.

Patient disposition from enrollment through 1-year follow-up by conditioning stratum. HSCT, hematopoietic stem cell transplantation; MAC, myeloablative conditioning; NMA, nonmyeloablative; RIC, reduced-intensity/nonmyeloablative conditioning.

FIG 2.

Overall survival at 1 year after transplantation by conditioning stratum. MAC, myeloablative conditioning; RIC, reduced-intensity/nonmyeloablative conditioning.

FIG 3.

Key secondary end points by conditioning stratum. (A) Cumulative incidence of acute GVHD grade 2 to 4 at 6 months after transplantation, (B) cumulative incidence of acute GVHD grade 3 to 4 at 6 months after transplantation, (C) cumulative incidence of chronic GVHD moderate/severe at 1 year after transplantation, and (D) cumulative incidence of relapse at 1 year after transplantation. GVHD, graft-versus-host disease; MAC, myeloablative conditioning; RIC, reduced-intensity/nonmyeloablative conditioning.