New Regimen Could Improve Outcomes in Transplantation From Half-Matched Donors

A regimen of post-transplant cyclophosphamide (PTCy), abatacept, and a short course of tacrolimus (CAST) after a peripheral blood haploidentical hematopoietic stem cell transplantation (HSCT) has showed good results with preventing graft-versus-host disease (GVHD). New research published in Transplantation and Cellular Therapy has confirmed these results and supports additional analysis into the regimen.

The initial results of the CAST regimen were first published in July 2023 in Blood Advances. In that study, the combination therapy after peripheral blood haploidentical HSCT was evaluated in a phase 1b/2 trial. A total of 46 patients were enrolled with a median follow-up of 15.3 months. The trial found the CAST regimen was associated with excellent rates of GVHD, nonrelapse mortality, relapse rate, overall survival, and GVHD- and relapse-free survival.

Haploidentical transplant uses healthy cells from a half-matched donor, typically a family member, to replace the patient’s unhealthy cells. The use of haploidentical HSCT has helped improve the likelihood that patients from certain minority groups find suitable donors, but the research has found outcomes after these haploidentical transplantation is inferior to human leukocyte antigen (HLA)-matched unrelated donor transplants, the authors explained.

HLA-matched donors are people who have HLAs similar to the patient’s HLAs. While the best HLA-matched donor is a close relative, siblings with the same parents still only have a 25% chance of being a full HLA match. The National Marrow Donor Program can help find HLA-matched unrelated donors, but the “underrepresentation of minorities in blood and marrow donor registries continues to pose a challenge for patients from certain racial and ethnic groups,” the researchers explained in the first CAST study.

In this newest study, the researchers used a propensity, score-matched analysis of the Center for International Blood and Marrow Transplant Research (CIBMTR) database. CIBMTR is a collaboration between the National Marrow Donor Program and the Medical College of Wisconsin. The study included patients who were in the original CAST study and patients from the database who received the standard GVHD prevention regimen of PTCy, tacrolimus, and mycophenolate mofetil from 2017 to August 2022.

At 120 days after treatment, the rate of acute GVHD grades 2-4 as 16.7% compared with 28.6% in the control cohort receiving the standard prevention regimen. In addition, the 1-year GVHD- and relapse-free survival rate was 66.7% in the CAST cohort compared with 47.6% in the control cohort. The authors noted that due to the small numbers of patients and events, the trend did not reach statistical significance.

However, CAST was associated with a statistically significant reduction in the incidence of relapse. The relapse rate was 9.5% for patients on CAST compared with 26.2% for patients on the standard regimen. CAST also led to a statistically significant improvement in disease-free survival (85.7%) compared with the standard treatment (61.0%).

Thus far, the need for HLA-matched donors has restricted the use of HSCT, which is the only curative therapy for high-risk and advanced hematological malignancies.

“This limitation disproportionately affects patients belonging to specific ethnic and racial groups, and it is particularly challenging for an increasing number of mixed-race individuals,” they noted. However, haploidentical donors are more readily available.

According to the authors, the CAST regimen can improve outcomes of haploidentical HSCT, which would reduce the disparities for patients who do not have readily available matched donors. They suggest that the data of this analysis support examining the CAST regimen in a randomized controlled trial.