MPN-075 Efficacy and Safety of Add-on Parsaclisib to Ruxolitinib Therapy in Myelofibrosis Patients With Low Versus Higher Baseline Platelet Counts: A Subgroup Analysis of Data From a Phase 2 Study

Abdulraheem Yacoub, Uma Borate, Raajit Rampal, Haris Ali, Eunice Wang, Aaron Gerds, Gabriela Hobbs, Marina Kremyanskaya, Elliott Winton, Casey O'Connell, Swati Goel, Stephen Oh, Gary Schiller, Albert Assad, Sue Erickson-Viitanen, Feng Zhou, Naval Daver

Research output: Contribution to journalArticlepeer-review

Abstract

Context: Ruxolitinib (JAK inhibitor) is effective in myelofibrosis, but suboptimal responses occur potentially from PI3K/AKT activation. In INCB50465-201 (NCT02718300), add-on parsaclisib (PI3Kδ inhibitor) showed preliminary efficacy in myelofibrosis patients. JAK inhibitors are associated with thrombocytopenia and patients with low platelet count (PC) are generally difficult to treat. Objective: Evaluate efficacy and safety of add-on parsaclisib in a subgroup analysis of study INCB50465-201 by baseline PC. Design: Open-label, phase 2. Setting: Clinical study. Patients: Primary/secondary myelofibrosis patients with a suboptimal response (palpable spleen >10 cm below left subcostal margin [LSM]; or palpable spleen 5-10 cm below LSM and active symptoms) after ≥6 months of receiving ruxolitinib (5-25 mg BID; stable dose ≥8 weeks). Interventions: Patients on stable ruxolitinib dose randomized to either add-on parsaclisib 10 or 20 mg QD for 8 weeks then same dose QW or parsaclisib 5 or 20 mg QD for 8 weeks then 5 mg QD. Main Outcome Measures: Spleen volume (SV), Myelofibrosis-Symptoms Assessment Form Total Symptom Score (MFSAF-TSS v3.0), and safety based on baseline PC (low PC, 50-<100×109/L; higher PC, ≥100×109/L). Results: At data cutoff (08/27/2020), 67 patients (low PC, n=21; higher PC, n=46) were enrolled. For low versus higher PC, the median prior duration of ruxolitinib treatment was 34.7 versus 14.9 months and baseline median (range) MFSAF-TSS was 21.4 (0.6–47) versus 10.0 (0–43), respectively. For low versus higher PC patients: 9/18 (50%) versus 15/38 (39.4%) had spleen volume reduction (SVR) ≥10% at week 12, 6/17 (35.2%) versus 13/35 (37.1%) at week 24; 0 versus 1 had SVR ≥35% at week 12, 2 versus 1 at week 24; median change in MFSAF-TSS was –20.5% versus –22.2% at week 12, –26.1% versus –23.1% at week 24, respectively. Nonhematologic treatment-emergent adverse events were mostly grade 1 or 2; most common (≥25%) were dyspnea (7/21, 33%), falls (7/21, 33%), and peripheral edema (6/21, 29%) for low PC; diarrhea (13/46, 28%) for higher PC. Thrombocytopenia led to parsaclisib interruption in 9/21 low-PC versus 3/46 higher-PC patients and ruxolitinib interruption in 1/21 low-PC patients. Conclusions: Add-on parsaclisib showed promising efficacy and combination therapy was generally well-tolerated in myelofibrosis patients with low or higher baseline PC.

Original languageEnglish (US)
Pages (from-to)S324
JournalClinical Lymphoma, Myeloma and Leukemia
Volume22
DOIs
StatePublished - Oct 2022

Keywords

  • MPN
  • myelofibrosis
  • Phase II
  • PI3K
  • platelet count
  • ruxolitinib

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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