Itacitinib + PTCy (haploidentical HCT)

Background

Open-label single-arm phase 1/2 study, N=42 undergoing T-cell-replete peripheral-blood haploidentical HCT. Tested adding selective JAK1 inhibitor itacitinib to PTCy-based prophylaxis to mitigate GVHD and cytokine release syndrome (both IFN-γ/IL-6, JAK1-driven).

Interventions and follow up

Treatment: Itacitinib 200 mg daily from day −3 through day +100 or +180 (then taper), added to standard PTCy-based GVHD prophylaxis after haploidentical HCT.
Primary endpoint: Safety and efficacy (CRS, GVHD, overall survival).
mFollow up: 1–2 year outcomes reported.

Results

CRS: All patients grade 0 (22%) or grade 1 (78%); no grade 2–5 CRS.
Acute GVHD: No grade 3–4 aGVHD through day +180; grade 2 aGVHD at day +100 21.9%.
Moderate-severe cGVHD (1-yr): 5%.
2-yr relapse: 14%.
1-yr OS: 80%.
NRM/TRM: day-180 NRM 8%.

Adverse events

Engraftment: No primary graft failures; itacitinib well tolerated on a PTCy backbone.
CRS: No grade 2–5 CRS occurred.
GVHD/NRM: Low rates of acute and chronic GVHD and non-relapse mortality.

Conclusions

Adding itacitinib to PTCy-based prophylaxis in haploidentical HCT produced very low rates of CRS, acute and chronic GVHD, and NRM, with encouraging GRFS and overall survival. Findings support further study of JAK1 inhibition in the haplo-HCT setting.

Key Limitations

Small single-arm phase 1/2 study (N=42) without a randomized comparator and limited follow-up. Single-center experience; benefit over PTCy alone must be confirmed in a randomized trial.

Clinical Context

Ruxolitinib (a related JAK1/2 inhibitor) is FDA/EMA-approved for steroid-refractory acute and chronic GVHD. Itacitinib is investigational for GVHD prophylaxis; these data add to growing interest in JAK inhibition for GVHD/CRS prevention on a PTCy backbone, complementing ASTCT prophylaxis frameworks.

References