Vorinostat for graft-versus-host disease prevention in pediatric and young adult patients with hematologic malignancies
Recommended Citation
Parnell N, Cao X, Beumer JH, Braun TM, Cui Y, Fisher GJ, Hou G, Holleran J, Churay T, Rozwadowski M, Heider L, Vander Lugt MT, Kitko CL, Rahrig AL, Peres E, Williams KM, Talano JA, Fabrizio VA, Abusin G, Yanik GA, Magenau J, Riwes M, Geer MJ, Anand S, Ghosh M, Pawarode A, Votruba K, Reddy P, Choi SW. Vorinostat for Graft-Versus-Host Disease Prevention in Pediatric and Young Adult Patients with Hematologic Malignancies. JCI Insight. 2026.
Document Type
Article
Publication Date
9-24-2026
Publication Title
JCI Insight
Abstract
BACKGROUND: This prospective, single-arm, multicenter phase 1/2 trial evaluated vorinostat added to standard graft-versus-host disease (GVHD) prophylaxis in pediatric, adolescent, and young adult (AYA) patients undergoing allogeneic hematopoietic cell transplantation (HCT) from HLA-matched related, HLA-matched unrelated, and haploidentical donors.
METHODS: Patients aged 3-39 years received twice-daily vorinostat with tacrolimus/methotrexate after HLA-matched HCT from day -10 to +30, or with post-transplant cyclophosphamide/tacrolimus/mycophenolate mofetil after haploidentical HCT from day +5 to +30. The primary endpoint was cumulative incidence of grade II-IV acute GVHD by day +100. All outcomes were based on intention-to-treat analysis.
RESULTS: Forty-three patients were enrolled; median age was 19 years, with 74% receiving HLA-matched and 26% haploidentical HCT. The recommended phase 2 dose was 60 mg/m² twice daily. No dose-limiting toxicities, unexpected vorinostat-related serious adverse events, or primary graft failures occurred. Median neutrophil and platelet recovery occurred at 14 and 18 days, respectively. Day +100 grade II-IV and III-IV acute GVHD were 14% (95% CI, 5.6, 26) and 4.7% (95% CI, 0.83, 14), respectively. One-year overall survival was 88.4% (95% CI, 79.3, 98.5), relapse 14% (95% CI: 5.6, 26), nonrelapse mortality 4.7% (95% CI: 0.8, 14), and GVHD-free/relapse-free survival 55.8% (95% CI: 42.8, 72.8). Correlative studies demonstrated on-target HDAC activity, with increased histone acetylation and lower proinflammatory cytokines.
CONCLUSION: These findings support randomized evaluation of vorinostat-based GVHD prophylaxis in pediatric and AYA HCT.
CLINICALTRIALS: gov, NCT03842696.
PubMed ID
42784255
ePublication
ePub ahead of print
