PTCy, Abatacept, and Tacrolimus for GVHD Prophylaxis

By Patrick Daly - Last Updated: December 14, 2022

Haploidentical blood and marrow transplantation (BMT) has significantly increased the number of eligible hematopoietic stem cell donors; however, the outcomes of these transplants are inferior to those seen in matched unrelated donor (MUD) transplants with posttransplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis in both.

Researchers, led by A. Samer Al-Homsi, evaluated PTCy, abatacept, and short course of tacrolimus (CAST). Their study, presented at the 64th ASH Annual Meeting and Exposition, suggested that CAST appeared safe and effective and yielded “excellent outcomes.” Al-Homsi also noted that CAST allowed for earlier discontinuation of tacrolimus, potentially reducing toxicities faced by patients with GVHD.

CAST Regimen Shows Promising Outcomes in Blood and Marrow Transplants

The prospective, single-center phase 1b/2 trial enrolled 46 patients with hematological malignancies undergoing haploidentical transplantation from a related donor with myeloablative conditioning and CAST for GVHD prevention. Three patients were excluded from the final analysis due to short follow-up.

At the data cutoff of July 29, 2022, the median follow-up in evaluable patients was 8.9 months. The median time to neutrophil engraftment was 18 days (range, 13-30 days), and all patients achieved full donor chimerism. Notably, tacrolimus was tapered in all but 5 patients from day 60 to day 90, per the study’s protocol.

Authors reported the cumulative incidence of acute GVHD of grade 2-3, 3-4, and 4 was 12.8%, 5.1%, and 0%, respectively, with death as the competing event. The cumulative incidence of moderate to severe chronic GVHD was 17.1%. The researchers noted all instances of acute GVHD except 1 were seen in the first 30 patients.

Based on Kaplan Meier analysis, Al-Homsi and colleagues estimated the following 1-year outcomes:

  • Relapse-free survival: 91.7% (95% CI, 83-100)
  • Overall survival: 90.6% (95% CI, 80.9-100.0)
  • GVHD-free, relapse-free survival: 71.8% (95% CI, 57.2-90.0)

Overall, the authors noted that no prespecified safety thresholds were reached and suggested that “CAST might be a step forward toward closing an important health disparity gap in BMT, equalizing the outcomes of haploidentical transplantation and MUD transplants.”

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