TY - JOUR
T1 - MPN-075 Efficacy and Safety of Add-on Parsaclisib to Ruxolitinib Therapy in Myelofibrosis Patients With Low Versus Higher Baseline Platelet Counts
T2 - A Subgroup Analysis of Data From a Phase 2 Study
AU - Yacoub, Abdulraheem
AU - Borate, Uma
AU - Rampal, Raajit
AU - Ali, Haris
AU - Wang, Eunice
AU - Gerds, Aaron
AU - Hobbs, Gabriela
AU - Kremyanskaya, Marina
AU - Winton, Elliott
AU - O'Connell, Casey
AU - Goel, Swati
AU - Oh, Stephen
AU - Schiller, Gary
AU - Assad, Albert
AU - Erickson-Viitanen, Sue
AU - Zhou, Feng
AU - Daver, Naval
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
KW - MPN
KW - PI3K
KW - Phase II
KW - myelofibrosis
KW - platelet count
KW - ruxolitinib
UR - http://www.scopus.com/inward/record.url?scp=85138148754&partnerID=8YFLogxK
U2 - 10.1016/S2152-2650(22)01433-1
DO - 10.1016/S2152-2650(22)01433-1
M3 - Article
C2 - 36163982
AN - SCOPUS:85138148754
SN - 2152-2650
VL - 22
SP - S324
JO - Clinical Lymphoma, Myeloma and Leukemia
JF - Clinical Lymphoma, Myeloma and Leukemia
ER -