Itacitinib (JAK1-selective) for GVHD prophylaxis

Current understanding

Itacitinib, a JAK1-selective inhibitor, is being evaluated in a phase IIa trial as an addition to standard tacrolimus/sirolimus GVHD prophylaxis for patients with acute leukemia, MDS, or myelofibrosis undergoing reduced-intensity conditioning allo-HSCT. The approach extends the JAK-inhibition-for-GVHD-prevention paradigm (established with ruxolitinib) to a more JAK1-selective agent, with the hypothesis that selective JAK1 blockade may preserve efficacy while reducing JAK2-mediated cytopenias. Efficacy and safety data from this early-phase study are pending.

Evidence log

• 2026-03-30 — Itacitinib, Tacrolimus, and Sirolimus for the Prevention of GVHD in Patients With Acute Leukemia, Myelodysplastic Syndrome, or Myelofibrosis Undergoing Reduced Intensity Conditioning Donor Stem Cell Transplantation: cross-connection with peritransplant-ruxolitinib-gvhd: Both investigate JAK inhibition for GVHD prevention in allo-HSCT; itacitinib’s JAK1-selectivity contrasts with ruxolitinib’s JAK1/2 dual inhibition, raising questions about whether selectivity affects the efficacy/cytopenia tradeoff in the peri-transplant setting. (novelty: 3)

Open questions

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