In a recent study, researchers from the Hope National Medical Center in Duarte, California, evaluated the safety and efficacy of adding itacitinib to standard graft-versus-host disease (GVHD) prophylaxis with tacrolimus or sirolimus in patients undergoing allogeneic hematopoietic cell transplants (HCT).
According to a presentation by lead author, Haris Ali, MD, at the 64th ASH Annual Meeting, early findings showed the combined itacitinib regimen had acceptable toxicity and yielded a low rate of acute GVHD.
Combining Itacitinib With Tacrolimus or Sirolimus for GVHD
This single-center, single-arm phase 2a trial included 59 patients (61% male) who received itacitinib at a dose of 200 mg per day. The primary end point for safety was toxicity, and for dose expansion was the rate of GVHD-free, relapse-free survival (GRFS) at 1 year. At the time of the presentation, 57 patients had completed 100 days of observation.
Over a median follow-up of 5.9 months (range, 0.6-12.4 months), there were no reports of unacceptable toxicities per prespecified criteria. Grade 3-4 adverse events in the first 100 days that were potentially related to itacitinib included:
- anemia (n=1)
- febrile neutropenia (n=2)
- abdominal pain (n=1)
- lymphocytopenia (n=8)
- neutropenia (n=1)
- thrombocytopenia (n=3)
- leukopenia (n=3)
- hypertriglyceridemia (n=1)
Acute GVHD of grade 2-4 was seen in 6 (10%) patients, and GVHD of grade 3-4 was seen in 5 (8%) patients. The estimated rates of GRFS at 6 months and 1 year were 0.71 (95% CI, 0.56-0.81) and 0.51 (95% CI, 0.31-0.68), respectively. The authors noted that itacitinib exposure in their data was significantly higher than published reports, suggesting an interaction with sirolimus.
“Early results of this phase 2 study indicated that itacitinib (200 mg daily) with tacrolimus/sirolimus GVHD prophylaxis was safe and tolerated, with 100% engraftment and low rate of acute GVHD without excessive toxicities,” the authors concluded.