Ruxolitinib/Abemaciclib Shows Encouraging Efficacy in Myelofibrosis

Combining ruxolitinib (Jakafi) with abemaciclib (Verzenio) demonstrated encouraging activity in a small cohort of patients with previously treated advanced myelofibrosis, according to findings from a phase 1 trial (NCT05714072) presented in a poster session at the 2026 American Association for Cancer Research AACR Annual Meeting.¹

Efficacy data revealed that 6 of 9 evaluable patients achieved white blood cell normalization by cycle 2; 6 of 7 evaluable patients showed normalization by cycle 6. Additionally, 7 of 7 patients evaluable for dose-limiting toxicities remain on the study and continue to receive abemaciclib at 100 mg or 150 mg. All evaluable patients maintained a spleen reduction volume of at least 25% (SVR25).

The median best SVR was 36.3% (range, 19.1%-48.6%), with 7 (77.8%) achieving SVR25 and 5 (55.6%) experiencing SVR35. MPN-SAF Total Symptom Score (TSS) reduction occurred in 7 of 9 patients at a median absolute change of –10 (range, –17 to 4). Furthermore, the study therapy correlated with stabilization or improvement of hemoglobin and platelet values.

“[Ruxolitinib] plus the CDK 4/6 inhibitor [abemaciclib] is safe and has encouraging objective evidence of efficacy among [patients] with advanced, previously treated [myelofibrosis],” lead study author Brian Chernak, MD, an assistant attending physician specializing in leukemia at Memorial Sloan Kettering Cancer Center, wrote with coauthors in the publication.¹ “[The] combination of [ruxolitinib/abemaciclib] will advance to a phase 2 study in previously treated [patients with myelofibrosis].”

Investigators of the dose-escalation phase 1 trial evaluated the safety of combining ruxolitinib with abemaciclib for patients with previously treated myelofibrosis as part of a 3+3 design. Patients received abemaciclib at 50 mg, 100 mg, or 150 mg twice daily plus fixed doses of ruxolitinib at 10 mg or 15 mg twice daily.

The trial’s primary end points were safety and the recommended phase 2 dose. Secondary end points included SVR25 and MPN-SAF TSS changes.

Patients 18 years and older with primary myelofibrosis or post-polycythemia vera or essential thrombocytopenia myelofibrosis requiring therapy and intermediate-1, -2, or high-risk disease per Dynamic International Prognostic Scoring System guidelines were eligible for enrollment on the trial.² Other eligibility criteria included having evidence of inadequate response to prior ruxolitinib, an ECOG performance status of 0 to 2, a life expectancy of at least 24 weeks, and adequate organ function. Those with prior receipt of CDK4/6 inhibitors, concomitant treatments with other investigational agents for myelofibrosis, or active central nervous system leukemia were ineligible for study entry.

As of March 1, 2026, 11 patients entered the study with a median age of 66 years (range, 54-76). The most common prior regimens included ruxolitinib monotherapy (100%), ruxolitinib plus pelabresib or placebo (36.4%), hydroxyurea (27.3%), and hypomethylating agents (22.2%). The most common molecular alterations included JAK2^V617F mutations (63.6%) and CALR mutations (27.3%). The median baseline spleen volume was 2303 cm³ (range, 531-3587), and the median MPN-SAF TSS was 33 (range, 14-47).

Patients received the study therapy for a median of 9.5 cycles (range, 3-23), and investigators observed no dose-limiting toxicities or serious adverse effects (AEs). The most common AEs regardless of attribution included diarrhea (80%), anemia (80%), and thrombocytopenia (70%). Grade 3 AEs included anemia (30%), decreased neutrophil counts (20%), and diarrhea (20%).

Additional safety data showed no AEs higher than grade 3. No patients discontinued study therapy due to toxicity. Investigators reported that 4 patients discontinued study treatment, including 1 who discontinued before the dose-limiting toxicity evaluable window.

References

1. Chernak B, Bewersdorf JP, Derkach A, et al. The combination of ruxolitinib and the CDK4/6 inhibitor abemaciclib demonstrates safety and efficacy in previously treated myelofibrosis patients: results of a phase I study. Presented at the 2026 American Association for Cancer Research Annual Meeting, San Diego, CA; April 17-22, 2026. Abstract CT191/13.
2. A study of ruxolitinib in combination with abemaciclib for the treatment of myelofibrosis. ClinicalTrials.gov. Updated November 18, 2025. Accessed April 22, 2026. https://tinyurl.com/3zrh5r38