# COMFORT-II: JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis

Source: https://onco.cc/key-papers/paper-comfort-ii-ruxolitinib-best-available-therapy-harrison-nejm-2012/  
OnCo record `paper-comfort-ii-ruxolitinib-best-available-therapy-harrison-nejm-2012` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

28 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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-22
- Journal: New England Journal of Medicine
- Year: 2012
- DOI: 10.1056/NEJMoa1110556
- Authors: Harrison C, Kiladjian JJ, Al-Ali HK, et al.
- 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.
- What it means: 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.

## Sources

- N Engl J Med 2012: https://doi.org/10.1056/NEJMoa1110556
- PubMed: https://pubmed.ncbi.nlm.nih.gov/22375970/

## Connected records

- cancers: [Myeloproliferative neoplasms (PV, ET, myelofibrosis)](https://onco.cc/cancers/myeloproliferative-neoplasms/), [Primary myelofibrosis](https://onco.cc/cancers/primary-myelofibrosis/)
- drugs: [Ruxolitinib](https://onco.cc/drugs/ruxolitinib/)
- trials: [COMFORT-II](https://onco.cc/trials/comfort-ii/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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