New Treatment Approach May Prevent GvHD in ‘Mismatched’ Blood Stem Cell Transplants

A new treatment strategy using post-transplant cyclophosphamide (PTCy) appears to prevent most cases of graft-versus-host disease (GvHD) in patients undergoing peripheral blood stem cell (PBSC) transplants from HLA-mismatched, unrelated donors (MMUDs). The findings, published last month in the Journal of Clinical Oncology, could represent a significant expansion of transplant eligibility for patients who lack a fully matched donor, including those from underrepresented racial and ethnic groups.

In the phase II, nonrandomized, multicenter ACCESS trial, investigators enrolled 145 adults with advanced hematologic malignancies across two conditioning strata: myeloablative (MAC) and reduced-intensity or nonmyeloablative (RIC/NMA). All participants received PBSC grafts and a GvHD prophylaxis regimen of PTCy, tacrolimus and mycophenolate mofetil. The primary outcome was 1-year overall survival for each stratum.

At a median follow-up of 12 months, 83.8% of patients in the MAC group and 78.6% of patients in the RIC/NMA group survived. At 6 months, the incidence of severe GvHD (grades III to IV) was 8% in the MAC group and 10% in the RIC/NMA group. At 1 year, moderate/severe chronic GvHD was 10.3% in the MAC group and 8.6% in the RIC/NMA group. Overall survival did not differ significantly by HLA match level (7/8 versus 4-6/8) in an exploratory analysis, although investigators noted the analysis was underpowered and, therefore, not definitive.

Importantly, 59% of trial participants self-identified as belonging to underrepresented racial or ethnic groups, and many had rare HLA types or came from socially vulnerable backgrounds. The findings suggest that MMUD transplants using PTCy could help address disparities in transplant access.

“Our focus on improving outcomes after MMUD HSCT was driven by knowledge that this donor type significantly expands access to curative therapy for all patients with blood cancers regardless of ancestry,” the researchers wrote.

In addition, the researchers emphasized that MMUD strategies make it easier to prioritize younger donors, which are associated with better transplant outcomes. All donors in the trial were under the age of 35, which the authors noted is “often not feasible when relying solely on 8/8 HLA-matched or even haploidentical donors.”

The authors concluded that while further studies are necessary to optimize the safety and effectiveness of HLA-mismatched donor HSCT, the findings demonstrate that “HSCT with MMUD PBSC and PTCy-based GvHD prophylaxis offers adult patients with advanced hematologic malignancies access to transplant with excellent outcomes.”