Preliminary Safety and Efficacy of Navitoclax Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Patients With Myelofibrosis From the Multicenter, Open-Label, Phase 2 Study (REFINE)
Recommended Citation
Passamonti F, Foran JM, Tandra A, De Stefano V, Fox ML, Mattour A, McMullin MF, Perkins AC, Rodriguez-Macías G, Sibai HA, Polepally AR, Sun Y, Chopra AS, Harb JG, Qin Q, Potluri J, How J. Preliminary Safety and Efficacy of Navitoclax Plus Ruxolitinib in Janus Kinase Inhibitor-Naïve Patients With Myelofibrosis From the Multicenter, Open-Label, Phase 2 Study (REFINE). Hematol Oncol. 2026;44(2):e70180.
Document Type
Article
Publication Date
3-1-2026
Publication Title
Hematological oncology
Keywords
Humans, Male, Nitriles, Primary Myelofibrosis, Female, Pyrazoles, Pyrimidines, Aged, Middle Aged, Aniline Compounds, Sulfonamides, Antineoplastic Combined Chemotherapy Protocols, Adult, Aged, 80 and over, Prognosis, Janus Kinase Inhibitors, Treatment Outcome
Abstract
Myelofibrosis is characterized by perturbation of the JAK/STAT pathway and upregulation of anti-apoptotic factors leading to myeloproliferation, bone marrow fibrosis (BMF), extramedullary hematopoiesis, splenomegaly, and cytopenias. Navitoclax, a potent oral B-cell lymphoma (BCL)-X(L)/BCL-2 inhibitor, promotes apoptosis of malignant myelofibrosis cells. Herein, we present results of Cohort 3 of the Phase 2 REFINE study (NCT03222609), which evaluated efficacy and safety of navitoclax plus ruxolitinib in JAKi-naïve patients with myelofibrosis. JAKi-naïve patients with primary or secondary myelofibrosis (≥ 18 years with splenomegaly, DIPSS intermediate-2 and high-risk myelofibrosis, and ECOG 0-2) and platelet count > 100 × 10(9)/L were enrolled and treated with navitoclax 100 mg once daily (QD) or 200 mg QD according to platelet count (≤ 150 × 10(9)/L or > 150 × 10(9)/L, respectively). Ruxolitinib was given twice daily (dose per label). Primary endpoint: spleen volume reduction of ≥ 35% (SVR(35)) at week 24. Secondary endpoints: ≥ 50% reduction in total symptom score (TSS(50)) at week 24, change in grade of BMF, anemia response, and safety. Thirty-two patients received ≥ 1 dose of navitoclax plus ruxolitinib. Median (range) duration of follow-up was 44 months (5-58). 63% (20/32) of patients achieved SVR(35) at week 24; median (range) time to first SVR(35) was 12 weeks (11─48). Of 24 evaluable patients, 21% achieved ≥ 50% reduction in driver gene variant allele frequency (VAF). Of 27 evaluable patients, 11 (41%) achieved TSS(50) at week 24; median (range) time to first TSS(50) of 3 weeks (0─16). BMF improved from baseline by ≥ 1 grade in 13/27 patients (48%) at any time on study. Anemia response rates were 38% (5/13) for transfusion-independent and 100% (2/2) for transfusion-dependent patients. No bleeding events or deaths were attributed to navitoclax. These findings suggest navitoclax plus ruxolitinib has a tolerable safety profile and provides clinically meaningful improvements for JAKi-naïve patients with myelofibrosis. TRIAL REGISTRATION: NCT03222609.
Medical Subject Headings
Humans; Male; Nitriles; Primary Myelofibrosis; Female; Pyrazoles; Pyrimidines; Aged; Middle Aged; Aniline Compounds; Sulfonamides; Antineoplastic Combined Chemotherapy Protocols; Adult; Aged, 80 and over; Prognosis; Janus Kinase Inhibitors; Treatment Outcome
PubMed ID
41846295
Volume
44
Issue
2
First Page
70180
Last Page
70180
