What does this research mean for the field?

Post-ruxolitinib Janus kinase inhibitors (fedratinib, momelotinib, and pacritinib) possess distinct efficacy and safety profiles that can guide individualized second-line treatment choices for patients with myelofibrosis. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To evaluate and compare the efficacy and safety of second-line Janus kinase inhibitors (fedratinib, momelotinib, and pacritinib) in patients with myelofibrosis who failed ruxolitinib.

August 16, 2026British Journal of HaematologyOpen Access

Janus kinase inhibitors after ruxolitinib failure in myelofibrosis: A systematic review and pooled analysis of phase 3 efficacy and integrated safety across clinical trials and real‐world evidence

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Authors

ADAndrea Duminuco PHPatrick Harrington ETElena Torre

Discussion

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Overview

Systematic review reveals distinct efficacy and safety profiles for second-line Janus kinase inhibitors in myelofibrosis, suggesting treatment should be tailored to patient phenotypes.

Key Points

To evaluate and compare the efficacy and safety of second-line Janus kinase inhibitors (fedratinib, momelotinib, and pacritinib) in patients with myelofibrosis who failed ruxolitinib.
Systematic search and pooled analysis of phase 3 clinical trials assessing efficacy (spleen volume reduction and total symptom score reduction at week 24).
Integrated safety analysis combining phase 2/3 trials (n = 1004) and real-world evidence cohorts (n = 790, including five momelotinib cohorts of n = 580).
Pooled ≥35% spleen volume reduction at week 24 was 32.7% (95% CI 27.3–38.6) for fedratinib, 15.8% (95% CI 11.7–21.0) for momelotinib, and 21.6% (95% CI 13.8–32.3) for pacritinib 200 mg twice daily; pooled ≥50% Total Symptom Score reduction was 32.8% (95% CI 27.4–38.7), 25.3% (95% CI 20.2–31.3), and 32.4% (95% CI 22.9–43.7), respectively.
Safety profiles differed: fedratinib had the highest grade ≥3 anaemia (34.3%) and diarrhoea (56.6%), pacritinib had the highest grade ≥3 bleeding (11.2%), and momelotinib showed the lowest grade ≥3 anaemia (8.0%) but real-world nephrotoxicity (17%–29%) and peripheral neuropathy (4%–20%).
Discontinuation rates due to adverse events were similar across all agents at approximately 16% to 17%.

Cite This Study

Duminuco et al. (2026) studied this question.

synapsesocial.com/papers/6a817ab4f2fb91fc834aeb41 https://doi.org/10.1111/bjh.70754

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August 16, 2026British Journal of HaematologyOpen Access

Janus kinase inhibitors after ruxolitinib failure in myelofibrosis: A systematic review and pooled analysis of phase 3 efficacy and integrated safety across clinical trials and real‐world evidence

View Full Paper

Ask AI

Bookmark

Authors

ADAndrea Duminuco PHPatrick Harrington ETElena Torre

Discussion

Member takes

Overview

Systematic review reveals distinct efficacy and safety profiles for second-line Janus kinase inhibitors in myelofibrosis, suggesting treatment should be tailored to patient phenotypes.

Key Points

To evaluate and compare the efficacy and safety of second-line Janus kinase inhibitors (fedratinib, momelotinib, and pacritinib) in patients with myelofibrosis who failed ruxolitinib.
Systematic search and pooled analysis of phase 3 clinical trials assessing efficacy (spleen volume reduction and total symptom score reduction at week 24).
Integrated safety analysis combining phase 2/3 trials (n = 1004) and real-world evidence cohorts (n = 790, including five momelotinib cohorts of n = 580).
Pooled ≥35% spleen volume reduction at week 24 was 32.7% (95% CI 27.3–38.6) for fedratinib, 15.8% (95% CI 11.7–21.0) for momelotinib, and 21.6% (95% CI 13.8–32.3) for pacritinib 200 mg twice daily; pooled ≥50% Total Symptom Score reduction was 32.8% (95% CI 27.4–38.7), 25.3% (95% CI 20.2–31.3), and 32.4% (95% CI 22.9–43.7), respectively.
Safety profiles differed: fedratinib had the highest grade ≥3 anaemia (34.3%) and diarrhoea (56.6%), pacritinib had the highest grade ≥3 bleeding (11.2%), and momelotinib showed the lowest grade ≥3 anaemia (8.0%) but real-world nephrotoxicity (17%–29%) and peripheral neuropathy (4%–20%).
Discontinuation rates due to adverse events were similar across all agents at approximately 16% to 17%.

Cite This Study

Duminuco et al. (2026) studied this question.

synapsesocial.com/papers/6a817ab4f2fb91fc834aeb41 https://doi.org/10.1111/bjh.70754

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