Ruxolitinib maintenance after allo-HCT

Background

Prospective multicenter single-arm phase 2 trial (78 enrolled, 63 treated) evaluating ruxolitinib (oral JAK1/2 inhibitor) as maintenance after reduced-intensity allogeneic HCT, on a tacrolimus + methotrexate prophylaxis backbone, aiming to reduce clinically significant chronic GVHD via prolonged JAK inhibition post-engraftment.

Interventions and follow up

Treatment: Standard tacrolimus + methotrexate prophylaxis, then ruxolitinib maintenance started day +30 to +100 (median day +45), continuous 28-day cycles for up to 24 cycles.
Primary endpoint: GVHD-free, relapse-free survival (GRFS) at 1 year.
mFollow up: 2-year outcomes reported.

Results

1-yr GRFS (primary): 70%.
Grade 3–4 acute GVHD (6 mo): 4.8%.
Moderate-severe cGVHD (2-yr): 16%; cGVHD requiring systemic therapy 9.5% at 1 yr, 13% at 2 yr.
2-yr OS: 76%.
2-yr PFS: 68%.
NRM / relapse: NR.

Adverse events

Hematologic: Most common grade ≥3 events were neutropenia, thrombocytopenia, and anemia.
Infections: 7 participants experienced grade ≥3 infectious events; regimen tolerable with most patients completing prolonged maintenance.

Conclusions

Prolonged ruxolitinib maintenance after reduced-intensity allo-HCT was associated with low rates of clinically significant chronic GVHD and favorable GRFS. Incorporating JAK inhibition into GVHD-prevention strategies warrants further investigation in randomized trials.

Key Limitations

Single-arm phase 2 study without a randomized comparator; 15 of 78 enrolled were never treated. GRFS benefit relative to standard prophylaxis can only be confirmed in a randomized trial; optimal maintenance duration undefined.

Clinical Context

Ruxolitinib is FDA/EMA-approved for steroid-refractory acute (REACH2) and chronic (REACH3) GVHD. This trial extends JAK1/2 inhibition into the prophylactic/maintenance space; consistent with PTCy-ruxolitinib data (Moiseev 2026), it supports ongoing randomized evaluation within ASTCT GVHD-prevention frameworks.

References