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Vorinostat plus standard immunoprophylaxis reduced GVHD after allogeneic HSCT
The addition of vorinostat to standard immunoprophylaxis reduced the incidence of graft-versus-host disease in patients with hematologic malignancies who underwent related-donor, reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation, according to results of a single-arm, phase 1/2 trial.
Fifty patients (median age, 59 years) with an 8/8 or 7/8 HLA-matched related donor were assessable for response and toxic effects. An additional eight patients were included in the toxic effects analysis.
All patients received a conditioning regimen that consisted of 40 mg/m2 daily fludarabine for 4 days, as well as 3.2 mg/kg daily busulfan for 2 days.
Researchers also administered standard immunoprophylaxis of 1 g mycophenolate mofetil three times a day on days 0 through 28, and 0.03 mg/kg daily tacrolimus — titrated to a goal level of 8 to 12 ng/mL — on days –3 to 180.
Treatment with vorinostat (Zolinza, Merck) commenced 10 days before HSCT and continued until day 100. Patients received twice-daily 100 mg or 200 mg doses.
Incidence of grade 2 through grade 4 acute GVHD by day 100 served as the primary endpoint.
All patients engrafted neutrophils and platelets after HSCT.
Researchers calculated a 22% cumulative incidence (95% CI, 13%-36%) of grade 2 to grade 4 acute GVHD.
Electrolyte disturbance (n=15), hyperglycemia (n=11), infections (n=6), mucositis (n=4) and increased activity of liver enzymes (n=3) were the most common non-hematologic adverse events.
Non-symptomatic thrombocytopenia after engraftment (n=9) was the most common hematologic grade 3 to grade 4 adverse event. All of these incidences were transient and resolved quickly, researchers wrote.
“Vorinostat combined with standard GVHD prophylaxis for patients undergoing related-donor reduced-intensity conditional HSCT is safe and feasible,” the researchers concluded. “This regimen, consistent with experimental observations, seems to result in a low cumulative incidence of clinically significant GVHD, without major adverse events. Further randomized trials are warranted to confirm these findings in this patient population and in broader HSCT settings.”
Disclosure: The researchers report no relevant financial disclosures.