Ruxolitinib (JAK1/2 inhibitor) Loses SVR35/TSS50 Ground When Early Cytopenias Emerge in MF

Ruxolitinib is an oral JAK1/2 inhibitor approved for myelofibrosis (MF), but dose intensity is often constrained by anemia and thrombocytopenia. In this post hoc analysis of the Phase 3 SIMPLIFY-1 trial (NCT01969838), 216 JAK inhibitor–naive MF patients treated with ruxolitinib were stratified by baseline anemia/thrombocytopenia and development of new or worsening (n/w) cytopenias within 12 weeks; week-24 endpoints were SVR35 and TSS50. N/w anemia occurred in 81.5% of baseline anemic (84/103) and 20.4% of baseline nonanemic patients (23/113) and was associated with relative SVR35 rate reductions of 13.5% and 21.4% (plus relative TSS50 reductions of 20.4% and 10.2%), alongside larger mean ruxolitinib dose reductions by week 12; baseline thrombocytopenia (39.8%, 86/216) was associated with relative SVR35 and TSS50 reductions of 69% and 24.4% vs baseline nonthrombocytopenic patients, with lower starting doses and further dose reductions if n/w thrombocytopenia developed. In broader ruxolitinib registration-era data, week-24 SVR35/TSS50 benchmarks were 42%/46% in COMFORT-I (vs placebo 1%/5%), highlighting how early cytopenias and dose modification can plausibly pull real-world outcomes below the “classic” efficacy expectations.