Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial.
Level 2 - randomized trial
Individual randomized controlled trial (phase 3 5-year follow-up update)
PubMed 28228106 · doi:10.1186/s13045-017-0417-z
What was done
This 5-year follow-up of the multicenter, double-blind, phase 3 COMFORT-I trial evaluated patients with intermediate-2 or high-risk myelofibrosis in Australia, Canada, and the USA. Patients were randomized 1:1 centrally via interactive voice response to oral ruxolitinib twice daily (15 or 20 mg based on baseline platelet count; n = 155) or placebo (n = 154). The secondary endpoints evaluated in the intent-to-treat population were durability of a ≥35% spleen volume reduction from baseline (spleen response) and overall survival. Safety was assessed in treated patients.
What was found
At study termination, 27.7% of ruxolitinib-randomized patients and 25.2% (28/111) who crossed over from placebo remained on treatment; zero patients remained on placebo. Ruxolitinib-assigned patients had a median spleen response duration of 168.3 weeks and prolonged median overall survival compared with placebo (ruxolitinib median not reached vs placebo 200 weeks; HR 0.69; 95% CI, 0.50–0.96; P = 0.025). The most frequent new-onset nonhematologic adverse events starting at <12 versus ≥48 months were fatigue (29.0% vs 33.3%) and diarrhea (27.8% vs 14.6%). New-onset grade 3/4 anemia and thrombocytopenia occurred primarily within the first 6 months, with zero new cases after 42 months. The most frequent adverse-event-related deaths in the ruxolitinib group were sepsis (2.6%), disease progression (1.9%), and pneumonia (1.9%).
Why it matters
These 5-year data confirm that ruxolitinib provides sustained spleen volume control and a persistent survival advantage over placebo in intermediate-2 and high-risk myelofibrosis, with cytopenias primarily occurring early rather than accumulating with prolonged exposure.
Limits
Survival comparison was confounded by crossover, as 111 of 154 placebo patients crossed over to ruxolitinib. Only 27.7% of the original ruxolitinib cohort remained on therapy at 5 years. Findings apply strictly to intermediate-2 and high-risk myelofibrosis and may not generalize to lower-risk populations.
Cited by
- supports Ruxolitinib is used in the treatment of the bone marrow disorder myelofibrosis.