Study shows mismatched unrelated donor (MMUD) HCT using PTCY and bone marrow is safe and effective
Use of MMUDs can expand HCT access for ethnically diverse populations
April 27, 2021
Key insights from the 15-MMUD study
- 48% of study participants were ethnically diverse; post-transplant outcomes were not significantly different across ethnicities. This proportion is typically much lower in HCT studies.
- Nearly 40% of study participants had <7/8 match; post-transplant outcomes were not significantly different between 7/8 and <7/8 match
- 75% survival rate after one year for the full population
- Researchers concluded expanding access to HCT using MMUDs is feasible and especially benefits patients who are ethnically diverse
- Outcomes of using MMUDs in the setting of PTCy are similar to those obtained using a related haploidentical donor
- Selecting a MMUD may have benefits over a haploidentical donor, such as removing risk associated with donor-specific antibodies and allowing for preferential selections of other favorable donor factors like younger age
- Research published in the Journal of Clinical Oncology
Summary of the 15-MMUD study
In the United States, 25 to 80% of patients with hematologic malignancies lack an HLA-matched (8/8 alleles) unrelated donor for hematopoietic cell transplantation (HCT) despite international registries listing more than 38 million volunteer donors and cord blood units. The greatest disparities are present in access for patients who are ethnically diverse.
The National Marrow Donor Program® (NMDP)/Be The Match® conducted a study between December 2016 and March 2019 at 11 transplant centers. The study enrolled 80 patients to assess the safety and efficacy of MMUD (4/8–7/8) HCT with bone marrow (BM) as a graft source. The patients were divided evenly into two groups:
- 40 received myeloablative HCT
- 40 received reduced intensity HCT
Approximately half of the study participants were ethnically diverse. Patients with a suitable HLA matched related or unrelated donor were excluded. The regimen intensity was at the center’s discretion.
The researchers aimed to determine 1-year overall survival (OS) after HLA MMUD bone marrow transplantation using PTCy, sirolimus and MMF to prevent GVHD. Patients received a fresh BM graft, followed by PTCY on days +3, +4, and sirolimus/MMF starting on day +5. The goal was to achieve a 65% or higher 1-year survival after HLA MMUD bone marrow transplantation. This is similar to the 1-year survival observed after HLA haploidentical related donor HCT using bone marrow as the graft source at the time the trial was launched. The secondary hypotheses were that greater than 90% of the individuals would engraft and the incidence of grades III-IV GVHD would be less than 15% at day +100.
15-MMUD study results
The results were encouraging with:
- 75% survival rate after 1 year
- Over 90% engraftment
- 11% rate of aGVHD III-IV at 100 days
The study population was composed of nearly 50% ethnically diverse patients. Nearly 40% of the cohort received <7/8 matched HCT.
15-MMUD study conclusions and a follow-up clinical trial
Selecting a MMUD expands donor options for patients and may have benefits over a related haploidentical donor, such as removing risk associated with donor specific antibodies and allowing for preferential selections of other favorable donor factors like younger age and blood type.
The researchers concluded expanding access to HCT, especially for patients who are ethnically diverse, using MMUDs is feasible as the outcomes of using MMUDs in the setting of PTCy are similar to those obtained using a related haploidentical donor. Access the full research paper published in the Journal of Clinical Oncology.
As a follow-up to the 15-MMUD study, the NMDP/Be The Match will be conducting the ACCESS clinical trial. The ACCESS study will assess whether transplant of a peripheral blood stem cell (PBSC) in adults or bone marrow product in children from a MMUD in combination with PTCy is safe, feasible and results in a high likelihood of overall survival. This could expand the approach to many more patients.