In a National Marrow Donor Program–sponsored phase II trial reported in the Journal of Clinical Oncology, Shaw et al found that a strategy of bone marrow hematopoietic cell transplant (HCT) from mismatched unrelated donors using posttransplant cyclophosphamide in patients with hematologic malignancies was feasible and effective in a population containing a high proportion of racial/ethnic minorities.
As noted by the investigators, despite the fact that unrelated donor registries contain more than 38 million volunteers, 25% to 80% of U.S. patients lack an HLA-matched unrelated donor, with patients from racial or ethnic minorities being disproportionately disadvantaged.
Our prospective study demonstrates the feasibility and effectiveness of HCT with a mismatched unrelated donor in the setting of [posttransplant] cyclophosphamide. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.— Shaw et al
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Study Details
The study included 80 patients enrolled at 11 U.S. transplant centers between December 2016 and March 2019. After myeloablative conditioning (n = 40) or reduced-intensity conditioning (n = 40), patients underwent transplantation and received posttransplant cyclophosphamide on posttransplant days 3 and 4 and started sirolimus and mycophenolate mofetil on day 5. Overall, 39% of donor-recipient pairs were matched for four to six of eight HLA alleles, and 48% of patients were from racial/ethnic minority groups. The primary endpoint was 1-year overall survival, with the endpoint considered met if the rate were ≥ 65%.
Key Findings
Overall survival at 1 year was 76% (90% confidence interval [CI] = 67.3%–83.3%) among all patients, including 72% (90% CI = 59.9%–83.1%) in the myeloablative conditioning cohort and 79% (90% CI = 66.9%–88.8%) in the reduced-intensity conditioning cohort. Rates were 75% (90% CI = 63.4%–84.3%) among patients matched for seven of eight HLA alleles and 77% (90% CI = 64.1%–88.4%) among those matched for four to six of eight alleles.
Primary graft failure was not observed in the myeloablative conditioning cohort and occurred in 7.5% of the reduced-intensity conditioning cohort.
Acute graft-vs-host disease of grade 2 to 4 and grade 3 to 4 at day 100 was observed in 43% and 18% of the myeloablative conditioning cohort and in 33% and 0% of the reduced-intensity conditioning cohort. Chronic graft-vs-host disease was observed in 36% of the myeloablative conditioning cohort and 18% of the reduced-intensity conditioning cohort.
Nonrelapse mortality and 1-year relapse rates were 8% and 30% in the myeloablative conditioning cohort and 10% and 23% in the reduced-intensity conditioning cohort.
No significant difference in 1-year overall survival (P = .761) was observed in multivariate analysis including the total study group and three cohorts of contemporary registry controls, consisting of patients receiving mismatched unrelated donor peripheral blood stem cell grafts (n = 143) or mismatched related donor recipients receiving bone marrow grafts (n = 398) or peripheral blood stem cell grafts (n = 1,191).
The investigators concluded, “Our prospective study demonstrates the feasibility and effectiveness of HCT with a mismatched unrelated donor in the setting of [posttransplant] cyclophosphamide. Remarkably, nearly half of the study participants belonged to an ethnic minority population, suggesting this approach may significantly expand access to HCT.”
Bronwen E. Shaw, MD, PhD, of CIBMTR/Froedtert & the Medical College of Wisconsin, Milwaukee, is the corresponding author for the Journal of Clinical Oncology article.
Dislcosure: The study was supported by The National Marrow Donor Program/Be The Match, the Be The Match Foundation, Center for International Blood and Marrow Transplant Research (CIBMTR), and others. For full disclosures of the study authors, visit ascopubs.org.
