On September 22, 2021, ruxolitinib, a tyrosine kinase inhibitor of JAK1 and JAK2 was granted approval for treatment of chronic graft-vs-host disease after failure of one or two lines of systemic therapy in adult and pediatric patients aged ≥ 12 years.1
Supporting Efficacy Data
Approval was supported by findings in the open-label, phase III REACH3 trial (ClinicalTrials.gov identifier NCT03112603), in which 329 patients with corticosteroid-refractory chronic graft-vs-host disease after allogeneic stem cell transplantation were randomly assigned to receive ruxolitinib at 10 mg twice daily (n = 165) or investigator-selected best available therapy (n = 164) in 28-day cycles.1
Overall response rate on 2014 National Institutes of Health Response Criteria through cycle 7, day 1 was 70% (95% confidence interval [CI] = 63%–77%) in the ruxolitinib group vs 57% (95% CI = 49%–65%) in the best available therapy group (difference = 13%, 95% CI = 3%–23%). Median duration of response (the time from first response to disease progression, death, or new systemic therapy for chronic graft-vs-host disease) was 4.2 months (95% CI = 3.2–6.7 months) vs 2.1 months (95% CI = 1.6–3.2 months). Median time from first response to death or new systemic therapy was 25 months (95% CI = 16.8 months to not estimable) vs 5.6 months (95% CI = 4.1–7.8 months).
KEY POINTS
- Ruxolitinib was granted approval for treatment of chronic graft-vs-host disease after failure of one or two lines of systemic therapy in adult and pediatric patients aged ≥ 12 years.
- The recommended ruxolitinib starting dose is 10 mg twice daily. Tapering of dose can be considered after 6 months of treatment in responding patients who have discontinued therapeutic doses of corticosteroids.
How It Is Used
The recommended starting dose of ruxolitinib is 10 mg twice daily. Tapering of dose can be considered after 6 months of treatment in responding patients who have discontinued therapeutic doses of corticosteroids.
Product labeling provides information on dosage modification, including dose reduction, for adverse reactions including thrombocytopenia, neutropenia, elevated bilirubin, and other grade 3 or 4 adverse reactions. Information is also provided on dosage modifications in concomitant use with strong CYP3A4 inhibitors (eg, clarithromycin, erythromycin, diltiazem) or fluconazole and in renal and hepatic impairment.
Safety Profile
Among patients in REACH3, the most common adverse events of any grade in the ruxolitinib group through cycle 7, day 1 were infections (pathogen not specified; 45% vs 44% in the best available therapy group), viral infections (28% vs 23%), and musculoskeletal pain (18% vs 13%). The most common grade 3 or 4 adverse events included infection (15% vs 16%), viral infection (5% vs 5%), and hypertension (5% vs 6%). Hematologic adverse events occurring in more than 35% of patients given ruxolitinib were anemia and thrombocytopenia.
Adverse events led to discontinuation of ruxolitinib in 18% of patients. Adverse events led to death in five patients treated with ruxolitinib, due to neutropenia, anemia, and/or thrombocytopenia in four and toxic epidermal necrolysis in one.
Ruxolitinib has warnings/precautions for thrombocytopenia, anemia, and neutropenia; risk of infection; symptom exacerbation following interruption or discontinuation of treatment; risk of nonmelanoma skin cancer; lipid elevations; major adverse cardiovascular events; thrombosis; and secondary malignancies. Patients should be advised not to breastfeed while receiving ruxolitinib.
REFERENCE
1. Jakafi (ruxolitinib) tablets prescribing information. Incyte Corp, September 2021. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/202192s023lbl.pdf. Accessed October 4, 2021.
