Itacitinib added to tacrolimus/sirolimus graft-versus-host disease (GVHD) prophylaxis after hematopoietic stem cell transplantation (HSCT) for acute leukemias, myelodysplastic syndrome (MDS), or myelofibrosis (MF) was safe and well-tolerated without excessive toxicities in a phase IIa, single-arm, single-center trial recently conducted at the City of Hope National Medical Center in Duarte, California.
The study was presented by lead author Haris Ali, MD, Department of Hematology and Hematopoietic Cell Transplantation, City of Hope National Medical Center, at the 64th American Society of Hematology Annual Meeting and Exposition.
For this trial, 59 participants (36 male and 23 female) were enrolled with a median age of 63 years (range, 23-75 years). Of those patients, 38 had acute leukemia, 17 had MDS, and 4 had MF. Participants underwent HSCT from a related (n=22) or unrelated (n=36) matched donor.
The authors hypothesized that itacitinib, when added to tacrolimus/sirolimus prophylaxis for GVHD, would safely improve GVHD nonrelapse survival. Itacitinib was administered at 200 mg/day along with the standard tacrolimus/sirolimus prophylaxis (target level, 5-10 ng/ml for both) starting at day 3 pre-HSCT and continuing until day 100+.
A total of 57 (97%) participants completed 100-day follow-up at the time the results were prepared. One patient died due to sepsis and multiple organ failure; no other patients died during the first 100 days. There were 20 grade III-IV adverse events possibly related to itacitinib, including anemia (n=1), febrile neutropenia (n=2), abdominal pain (n=1), lymphocytopenia (n=8), neutropenia (n=1), thrombocytopenia (n=3), leukopenia (n=3), and hypertriglyceridemia (n=1). In addition, 12 bacterial, 5 viral, and 2 fungal infections were reported.
Acute GVHD grade II-IV occurred in 6 patients and grade III-IV occurred in 5. When all adverse events were factored (all-cause mortality, n=9; grade III-IV acute GVHD, n=5; moderate/severe chronic GVHD, n=2; disease relapse, n=8), the authors estimated 1-year GVHD nonrelapse survival to be 0.51 (95% CI, 0.31-0.68), with 6-month survival at 0.71 (95% CI, 0.56-0.81).
Pharmacokinetic analyses showed that “measured itacitinib exposure [was] significantly higher than previously reported results, indicating a potential drug interaction with sirolimus,” according to Dr. Ali and his team.
“Early results of this phase II 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,” said Dr. Ali. “Early survival data, including preliminary [GVHD-free, relapse-free survival] are promising,” he added.
Ali H, Yang D, Mokhtari S, et al. Phase IIa study of adding itacitinib to tacrolimus/sirolimus Gvhd prophylaxis after fludarabine/melphalan-based conditioning hematopoietic cell transplantation for acute leukemias, myelodysplastic syndrome, or myelofibrosis. Abstract #772. Presented at the 64th ASH Annual Meeting and Exposition; December 10-13, 2022; New Orleans, Louisiana.