{"entity":{"id":"paper-comfort-ii-ruxolitinib-best-available-therapy-harrison-nejm-2012","kind":"paper","name":"COMFORT-II: JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis","aka":[],"tldr":"In this European trial, ruxolitinib shrank the spleen by more than a third in 28 percent of people with myelofibrosis after 48 weeks while no patient on the best alternative treatment achieved that, and symptoms and quality of life improved.","summary":"Open-label phase 3 trial that randomised 219 patients with intermediate-2 or high-risk primary, post-polycythaemia vera or post-essential thrombocythaemia myelofibrosis two to one to oral ruxolitinib or best available therapy. The primary endpoint was a spleen volume reduction of at least 35 percent at week 48 on MRI or CT; the key secondary endpoint was the same reduction at week 24.\n\n28 percent of the ruxolitinib group met the primary endpoint against 0 percent on best available therapy; responses were durable and role functioning and quality of life improved, with modest toxic effects. An influence on overall survival had not been shown at the primary analysis.","asOf":"2026-09-22","links":[{"label":"N Engl J Med 2012","url":"https://doi.org/10.1056/NEJMoa1110556"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/22375970/"}],"tags":[],"related":[],"cancers":["primary-myelofibrosis","myeloproliferative-neoplasms"],"sections":[],"technologies":[],"targets":[],"drugs":["ruxolitinib"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["comfort-ii"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2012,"doi":"10.1056/NEJMoa1110556","pmid":"22375970","authors":"Harrison C, Kiladjian JJ, Al-Ali HK, et al.","paperType":"rct","findings":["Spleen volume reduction of at least 35 percent at week 48 in 28 percent of patients on ruxolitinib versus 0 percent on best available therapy (p < 0.001).","Durable reductions in splenomegaly and disease-related symptoms, with improved role functioning and quality of life.","Modest toxic effects, mainly anaemia and thrombocytopenia."],"whatItMeans":"With COMFORT-I, the evidence for ruxolitinib as the first approved treatment for myelofibrosis and for JAK inhibition as the standard for spleen and symptom control.","caveats":["Open-label against a heterogeneous comparator, mostly hydroxycarbamide or no treatment.","No survival benefit was demonstrated at the primary analysis; pooled long-term follow-up later suggested one."],"changedPractice":true,"participants":219},"route":"/key-papers/paper-comfort-ii-ruxolitinib-best-available-therapy-harrison-nejm-2012/","neighbours":{"cancer":[{"id":"myeloproliferative-neoplasms","kind":"cancer","name":"Myeloproliferative neoplasms (PV, ET, myelofibrosis)","route":"/cancers/myeloproliferative-neoplasms/"},{"id":"primary-myelofibrosis","kind":"cancer","name":"Primary myelofibrosis","route":"/cancers/primary-myelofibrosis/"}],"drug":[{"id":"ruxolitinib","kind":"drug","name":"Ruxolitinib","route":"/drugs/ruxolitinib/"}],"trial":[{"id":"comfort-ii","kind":"trial","name":"COMFORT-II","route":"/trials/comfort-ii/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}]}}