Phase 2 study of add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib: final results

作者：Abdulraheem Yacoub, Uma Borate, Raajit K. Rampal, Haris Ali, Eunice S. Wang, Aaron T. Gerds, Gabriela Hobbs, Marina Kremyanskaya, Elliott F. Winton, Casey L. O’Connell, Swati Goel, Stephen T. Oh, Gary J. Schiller, James McCloskey, Jeanne Palmer, Houston Holmes, Steven Hager, Albert Assad, Susan Erickson‐Viitanen, Feng Zhou, Naval Daver · 发表于：Blood Advances · 年份：2024 · DOI：10.1182/bloodadvances.2023011620 · 被引用次数：14 · 研究领域：Myeloproliferative Neoplasms: Diagnosis and Treatment、Kruppel-like factors research、Chronic Myeloid Leukemia Treatments

ABSTRACT: Ruxolitinib reduces spleen volume, improves symptoms, and increases survival in patients with intermediate- or high-risk myelofibrosis. However, suboptimal response may occur, potentially because of signaling via the phosphoinositide 3-kinase (PI3K)/protein kinase B pathway. This phase 2 study evaluated dosing, efficacy, and safety of add-on PI3Kδ inhibitor parsaclisib for patients with primary or secondary myelofibrosis with suboptimal response to ruxolitinib. Eligible patients remained on a stable ruxolitinib dose and received add-on parsaclisib 10 or 20 mg, once daily for 8 weeks, and once weekly thereafter (daily-to-weekly dosing; n = 32); or parsaclisib 5 or 20 mg, once daily for 8 weeks, then 5 mg once daily thereafter (all-daily dosing; n = 42). Proportion of patients achieving a ≥10% decrease in spleen volume at 12 weeks was 28% for daily-to-weekly dosing and 59.5% for all-daily dosing. Proportions of patients achieving ≥50% decrease at week 12 in Myelofibrosis Symptom Assessment Form and Myeloproliferative Neoplasms Symptom Assessment Form symptom scores were 14% and 18% for daily-to-weekly dosing, and 28% and 32% for all-daily dosing, respectively. Most common nonhematologic treatment-emergent adverse events were nausea (23%), diarrhea (22%), abdominal pain and fatigue (each 19%), and cough and dyspnea (each 18%). New-onset grade 3 and 4 thrombocytopenia were observed in 19% of patients, each dosed daily-to-weekly, and in 26% and 7% of patients dosed all-d...