Post-Transplant Cyclophosphamide-Based Graft-Versus-host Disease Prophylaxis Following Mismatched Unrelated Donor Peripheral Blood Stem Cell Transplantation Using Myeloablative Conditioning – Results from the Access Trial

Abstract

Introduction

Our prior prospective multi-center clinical trial (15-MMUD) reported 72% overall survival (OS) at one year in adult patients with hematological malignancies undergoing myeloablative conditioning (MAC) and bone marrow (BM) grafts from HLA-mismatched unrelated donors (MMUD) and post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis (Shaw, J Clin Oncol 2021).

Objectives

We sought to determine whether OS in adults receiving mobilized peripheral blood stem cells (PBSC) from MMUD would be comparable.

Methods

We conducted a prospective, multi-center Phase II study (NCT04904588) to assess the impact of PTCy-based GVHD prophylaxis on OS following MMUD transplantation in adults and children with advanced hematological malignancies. The study included three strata: two adult cohorts based on conditioning regimen intensity [MAC (N=75) or reduced intensity conditioning (RIC; N= 193)] using PBSC, and one pediatric cohort using MAC and BM (still enrolling). Donors were matched at 4-7/8 HLA-loci (HLA -A, -B, -C, and -DRB1) and ≤ 35 years old. The primary endpoint was OS at one year following transplantation. Here, we report the analysis results of all 75 adult patients enrolled on the MAC PBSC stratum.

Results

Eighteen sites enrolled 75 patients with the following demographics: median age of 46 years (range 20-65); 60% male; diagnoses: AML (44%), ALL (39%), MDS (12%), other heme malignancies (5%); Patient race/ethnicity: non-Hispanic white (29%). Donor characteristics included: median age 25y (range 18-34); male (44%); and HLA match level: 7/8: 69%; 6/8: 25%; 5/8: 4%; 4/8: 1%. Conditioning regimens included fludarabine (flu) and busulfan (49%) and flu/TBI (51%). OS at one year post HCT was 84% (95% confidence interval (CI): 73-90%). Secondary endpoints are provided in Table 1.

Conclusion

OS observed at one year following MMUD PBSC in patients receiving MAC and PTCy was encouraging and appears similar to historical data in MAC recipients of HLA-matched donor PBSC grafts. Notably, 71% of enrolled patients were non-white or Hispanic. OS compares favorably relative to our prior study using BM grafts. Rates of GVHD and other complications were also in the range of those observed in HLA-matched donor recipients, suggesting MMUD HCT expands access to a potentially life-saving therapy for all patients regardless of ancestry. Accrual to both adult strata of ACCESS is complete, with analysis of the full adult RIC stratum planned for later this year.