Gecacitinib (JAK/ACVR1 inhibitor) for aGVHD prophylaxis

Current understanding

Gecacitinib hydrochloride is a novel dual JAK/ACVR1 inhibitor being evaluated, in combination with ATG, for prophylaxis of acute GVHD in myelofibrosis patients undergoing allogeneic HSCT. The dual mechanism is hypothesized to address both JAK-driven inflammatory pathways implicated in GVHD and ACVR1/hepcidin-related pathology relevant to MF biology, potentially differentiating it from ruxolitinib-based peri-transplant strategies. Evidence is currently early-trial stage.

Evidence log

• 2026-03-31 — Momelotinib During and After HCT in Myelofibrosis: cross-connection with peritransplant-momelotinib: Both momelotinib and gecacitinib are JAK/ACVR1 dual-pathway inhibitors being trialed in the peri-transplant MF setting, establishing a shared mechanistic class distinct from ruxolitinib-based strategies. (novelty: 3)
• 2026-03-13 — Gecacitinib Pre-, During- and Post-HSCT for Patients With Primary or Secondary Myelofibrosis: Trial extending gecacitinib across the full peri-transplant window (pre-, during-, and post-HSCT) in primary/secondary MF, broadening prior aGVHD-prophylaxis-only use into a comprehensive bridging + prophylaxis + maintenance protocol analogous to peritransplant ruxolitinib. (novelty: 3)
• 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 itacitinib-gvhd-prophylaxis: Itacitinib (JAK1-selective) and gecacitinib (JAK/ACVR1 dual) represent diverging strategies within the JAK-inhibitor GVHD prophylaxis space — increased selectivity versus broadened pathway coverage — relative to the ruxolitinib precedent. (novelty: 3)
• 2026-02-27 — Efficacy and Safety of Gecacitinib Hydrochloride in Prophylaxis Acute Graft-Versus-Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation in Patients With Myelofibrosis: cross-connection with peritransplant-ruxolitinib-gvhd: Both explore JAK-pathway inhibition for peri-transplant GVHD prevention in MF; gecacitinib adds ACVR1 inhibition as a differentiator from ruxolitinib. (novelty: 4)

Open questions

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