Vorinostat Can Lead to Lower Incidence of Acute GVHD

Adding vorinostat to a standard pre-transplant graft-versus-host disease (GVHD) prophylaxis can significantly lower the incidence of acute GVHD, according to results of a prospective, phase II study.

The study enrolled 37 patients with acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome who underwent myeloablative hematopoietic cell transplantation (HCT) from an available 8/8-HLA matched unrelated donor.

Vorinostat (100 mg twice daily) was started on day -10 and continued through day +100 post-HCT, and was in addition to a standard GVHD prophylaxis of tacrolimus and methotrexate.

The cumulative incidence of grade II-IV acute GVHD at day 100 was 22% and grade III-IV was 8%. The cumulative incidence of chronic GVHD was 29%. Relapse, non-relapse mortality, GVHD-free relapse-free survival, and overall survival (OS) at one year were 19%, 16%, 47%, and 76%, respectively.

The researchers noted that these data compare favorably with results of a large, multi-center study of 1,328 patients with AML who received unrelated donor HCT, where one-year OS was 40-50%. They acknowledged the low incidence of chronic GVHD may have be influenced by use of bone marrow grafts in 47% of the cohort, which has been previously shown to be associated with lower GVHD rates than peripheral blood grafts.

The researchers concluded that based on low acute GVHD rates, “vorinostat for GVHD prevention is an effective strategy that should be confirmed in a randomized phase III study.”

Choi SW, et al. Blood

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