Ruxolitinib + Abemaciclib (CDK4/6) Shows 44% SVR35 in Rux-Inadequate-Response Myelofibrosis

Ruxolitinib (a JAK1/2 inhibitor) was combined with abemaciclib (an oral CDK4/6 inhibitor that blocks G1/S cell-cycle progression) in a Phase I 3+3 dose-escalation study in previously treated myelofibrosis with inadequate response to ≥12 weeks of ruxolitinib (NCT05714072; n=11; 9 efficacy-evaluable; all DIPSS intermediate/high risk; median baseline spleen volume 1991cm³; median MPN-SAF TSS 33). As of the 11/30/2025 cutoff, no DLTs and no AE-related discontinuations were reported; grade 3 anemia occurred in 2 patients and grade 3 neutropenia in 1, while common TEAEs were diarrhea (62.5%), anemia (25%), and neutropenia (25%). Efficacy signals included SVR25 in 78% (7/9) and SVR35 in 44% (4/9) with median spleen volume change −31%, alongside modest symptom improvement (median absolute TSS change −4), which numerically sits in the neighborhood of first-line ruxolitinib SVR35 ≈42% at week 24 in COMFORT-I (but here in a tiny, rux-exposed/inadequate-response population with no control arm).