Background
Phase 1/2, open-label, single-arm study (REACH4). 45 pediatric patients with steroid-refractory acute GVHD (SR-aGVHD, grade II–IV) after allo-HCT. Based on REACH2 (adults) showing ruxolitinib — a JAK1/2 inhibitor — superior to best available therapy for SR-aGVHD. Ruxolitinib modulates JAK-STAT cytokine signaling dysregulated in GVHD. REACH4 established the pediatric dose and efficacy for FDA approval in this age group.
Interventions and follow up
Regimen: ruxolitinib weight-based oral dosing twice daily added to corticosteroids ± other immunosuppression for SR-aGVHD
Primary endpoint: Overall response rate (CR + PR) at day 28
Median follow up: 6 months
Primary endpoint: Overall response rate (CR + PR) at day 28
Median follow up: 6 months
Results
ORR at day 28 (primary): 75.6% (95% CI 60.5–87.1%)
CR rate at day 28: 44.4%
Best ORR: 84.4%
6-month failure-free survival: 46.5%
6-month OS: 69.8%
CR rate at day 28: 44.4%
Best ORR: 84.4%
6-month failure-free survival: 46.5%
6-month OS: 69.8%
Adverse events
Hematologic: grade ≥3 anemia 22.2%, thrombocytopenia 24.4%, neutropenia 17.8%
Infections: grade ≥3 infections 48.9% (CMV reactivation 17.8%, bacterial infections 26.7%)
Other: no unexpected safety signals beyond REACH2 adult data; weight-based dosing well tolerated across age groups
Infections: grade ≥3 infections 48.9% (CMV reactivation 17.8%, bacterial infections 26.7%)
Other: no unexpected safety signals beyond REACH2 adult data; weight-based dosing well tolerated across age groups
Conclusions
Ruxolitinib demonstrated a 75.6% ORR at day 28 in pediatric SR-aGVHD, consistent with adult REACH2 data, establishing ruxolitinib with a weight-based regimen as a standard therapy for SR-aGVHD in pediatric patients.
Key Limitations
Single-arm, non-randomized design with no active comparator; small sample (n=45) limits precision and subgroup analysis. Short median follow-up (6 months) precludes durable-response and long-term OS assessment. Cytopenias and infections (including CMV reactivation) are notable on-target/immunosuppression effects requiring monitoring. Efficacy is extrapolated in part from the adult REACH2 randomized experience rather than a pediatric controlled comparison.
Clinical Context
Ruxolitinib (Jakafi) was FDA-approved for SR-aGVHD in patients ≥12 years in 2019 based on REACH1/REACH2; REACH4 establishes age-appropriate weight-based dosing and efficacy extending use to younger children (≥2 years). Ruxolitinib is the established second-line standard for SR-aGVHD per ASTCT practice. The data support JAK1/2 inhibition as the backbone for steroid-refractory acute GVHD across the pediatric age range.