REFINE phase II: Navitoclax + ruxolitinib for JAKi-naïve MF

Results from Cohort 3 of the multicenter, open-label, phase II REFINE study (NCT03222609), evaluating the efficacy and safety of navitoclax + ruxolitinib in adults with Janus kinase inhibitor (JAKi)-naïve primary or secondary myelofibrosis (MF; N = 32), were published in Hematological Oncology by Passamonti et al. Patients received navitoclax 100 mg or 200 mg once daily (QD) according to baseline platelet count (≤150 × 10⁹/L or >150 × 10⁹/L, respectively) and ruxolitinib twice daily (BD), with ruxolitinib starting dose based on baseline platelet count per local label. The primary endpoint was a spleen volume reduction of ≥35% (SVR35) at Week 24. 

Key data: With a median follow-up of 44 months, SVR35 at Week 24 was achieved in 63% of patients; median time to first SVR35 was 12 weeks. SVR35 was achieved at any time in 81% of patients, and all patients had spleen volume reduction during treatment. A ≥50% reduction in total symptom score (TSS50) was achieved in 34% of patients at Week 24 and 56% at any time. Bone marrow fibrosis (BMF) improved by ≥1 grade in 30% of evaluable patients at Week 24 (7/23) and 48% at any time (13/27). A ≥50% reduction in driver gene variant allele frequency (VAF) occurred in 21% of evaluable patients (n = 24) at Week 24. Anemia response occurred in 47% of evaluable patients (n = 15), including 38% of transfusion-independent patients with baseline hemoglobin <10 g/dL (n = 13) and 100% of transfusion-dependent patients (n = 2). Grade ≥3 adverse events (AEs) occurred in 88% of patients; the most common were thrombocytopenia (38%), anemia (38%), and neutropenia (25%). 

Key learning: Navitoclax + ruxolitinib demonstrated a manageable safety profile and clinically meaningful improvements in patients with JAKi-naïve MF, supporting continued evaluation, while emphasizing the importance of cytopenia monitoring and individualized dose modification.