Vorinostat for GvHD prophylaxis in pediatric and AYA patients undergoing allo-HSCT

Results from a prospective, single-arm, multicenter, phase I/II trial (NCT03842696) evaluating vorinostat added to standard graft-versus-host disease (GvHD) prophylaxis in pediatric, adolescent, and young adult (AYA) patients with hematologic malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) from human leukocyte antigen (HLA)-matched related, HLA-matched unrelated, and haploidentical donors were published in JCI Insight by Parnell et al. The primary endpoint was the cumulative incidence of Grade 2–4 acute GvHD (aGvHD) at Day +100 in the phase II cohort.

Key data: In phase I (n = 6), vorinostat 60 mg/m² twice daily was established as the recommended phase II dose (RP2D). In the total treated cohort (N = 43), median neutrophil and platelet recovery occurred at 14 and 18 days, respectively. In phase II (n = 37), the Day +100 cumulative incidence of Grade 2–4 aGvHD was 16%. In the total treated cohort, the Day +100 cumulative incidence of Grade 2–4 and Grade 3–4 aGvHD was 14% and 4.7%, respectively. At 1 year, overall survival (OS) was 88.4%, relapse incidence was 14%, non-relapse mortality (NRM) was 4.7%, and GvHD-free, relapse-free survival (GRFS) was 55.8%. There were no deaths or unexpected serious adverse events (SAEs) considered related to vorinostat. 

Key learning: In this study, vorinostat combined with standard GvHD prophylaxis was associated with a low cumulative incidence of aGvHD by Day +100 and an acceptable safety profile in pediatric and AYA patients undergoing allo-HSCT across HLA-matched and haploidentical donor settings. These findings support further evaluation of vorinostat-based GvHD prophylaxis in a randomized trial.