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Addition of navitoclax to ruxolitinib for patients with myelofibrosis with progression or suboptimal response
Pemmaraju, N. Somervaille, T. C. P. Palandri, F. Harrison, C. Komrokji, R. S. Perkins, A. Ayala Diaz, R. M. Lavie, D. Tomita, A. Feng, Y.
Pemmaraju, N.
Somervaille, T. C. P.
Palandri, F.
Harrison, C.
Komrokji, R. S.
Perkins, A.
Ayala Diaz, R. M.
Lavie, D.
Tomita, A.
Feng, Y.
Abstract
Navitoclax (oral B-cell lymphoma-2 family protein inhibitor induces apoptosis of malignant cells in myelofibrosis (MF). We present pooled cohort 1 results from the phase 2 REFINE trial, which evaluated navitoclax plus ruxolitinib (NAV+RUX) for patients with relapsed/refractory MF with suboptimal response to RUX (≥10 mg twice daily stable dose for ≥12 weeks [cohort 1a] or ≥24 weeks [cohort 1b]). Cohort 1a received add-on NAV 50 mg/d, with escalation to ≤300 mg if platelet count was ≥75 × 10(9)/L. Cohort 1b received NAV 100 or 200 mg/d if platelet count was ≤150 or >150 × 10(9)/L, respectively. The primary end point was spleen volume reduction of ≥35% (SVR(35)) at week 24. Secondary end points included ≥50% total symptoms score (TSS(50)) reduction at week 24, bone marrow fibrosis (BMF) grade changes, anemia response, and safety. In total, 125 patients received ≥1 dose of NAV+RUX. With median follow-up of 21 months, SVR(35) rate was 23% at week 24 and 39% at any time on study (median duration: 11 months). TSS(50) rate was 24% at week 24 and 46% at any time on study. BMF improved by ≥1 grade, any time on study, in 39% of patients. Anemia responses were achieved in 23% of patients. Median overall and progression-free survival were 52.3 and 22.1 months, respectively. No new safety signals were observed. The most common adverse event was thrombocytopenia without clinically significant bleeding. NAV+RUX was tolerable and demonstrated early improvement in disease modification parameters in this difficult-to-treat population. This trial was registered at www.ClinicalTrials.gov as #NCT03222609.
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Date
2025
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Citation
Pemmaraju N, Somervaille TCP, Palandri F, Harrison C, Komrokji RS, Perkins A, et al. Addition of navitoclax to ruxolitinib for patients with myelofibrosis with progression or suboptimal response. Blood neoplasia. 2025 Feb;2(1):100056. PubMed PMID: 40454409. Pubmed Central PMCID: PMC12082167