Phase 2 study of add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib : final results
© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved..
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-daily, respectively, managed with dose interruptions. Hemoglobin levels remained steady. The addition of parsaclisib to stable-dose ruxolitinib can reduce splenomegaly and improve symptoms, with manageable toxicity in patients with myelofibrosis with suboptimal response to ruxolitinib. This trial was registered at www.clinicaltrials.gov as #NCT02718300.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
Blood advances - 8(2024), 6 vom: 26. März, Seite 1515-1528 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Yacoub, Abdulraheem [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
82S8X8XX8H |
|---|
| Anmerkungen: |
Date Completed 19.03.2024 Date Revised 29.03.2024 published: Print ClinicalTrials.gov: NCT02718300 Citation Status MEDLINE |
|---|
| doi: |
10.1182/bloodadvances.2023011620 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM367804514 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM367804514 | ||
| 003 | DE-627 | ||
| 005 | 20240330000844.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240131s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1182/bloodadvances.2023011620 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1355.xml |
| 035 | |a (DE-627)NLM367804514 | ||
| 035 | |a (NLM)38290135 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Yacoub, Abdulraheem |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Phase 2 study of add-on parsaclisib for patients with myelofibrosis and suboptimal response to ruxolitinib |b final results |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 19.03.2024 | ||
| 500 | |a Date Revised 29.03.2024 | ||
| 500 | |a published: Print | ||
| 500 | |a ClinicalTrials.gov: NCT02718300 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. | ||
| 520 | |a 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-daily, respectively, managed with dose interruptions. Hemoglobin levels remained steady. The addition of parsaclisib to stable-dose ruxolitinib can reduce splenomegaly and improve symptoms, with manageable toxicity in patients with myelofibrosis with suboptimal response to ruxolitinib. This trial was registered at www.clinicaltrials.gov as #NCT02718300 | ||
| 650 | 4 | |a Clinical Trial, Phase II | |
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a ruxolitinib |2 NLM | |
| 650 | 7 | |a 82S8X8XX8H |2 NLM | |
| 650 | 7 | |a parsaclisib |2 NLM | |
| 650 | 7 | |a OS7097575K |2 NLM | |
| 650 | 7 | |a Phosphatidylinositol 3-Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.1.- |2 NLM | |
| 650 | 7 | |a Pyrazoles |2 NLM | |
| 650 | 7 | |a Nitriles |2 NLM | |
| 650 | 7 | |a Pyrimidines |2 NLM | |
| 650 | 7 | |a Pyrrolidines |2 NLM | |
| 700 | 1 | |a Borate, Uma |e verfasserin |4 aut | |
| 700 | 1 | |a Rampal, Raajit K |e verfasserin |4 aut | |
| 700 | 1 | |a Ali, Haris |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Eunice S |e verfasserin |4 aut | |
| 700 | 1 | |a Gerds, Aaron T |e verfasserin |4 aut | |
| 700 | 1 | |a Hobbs, Gabriela |e verfasserin |4 aut | |
| 700 | 1 | |a Kremyanskaya, Marina |e verfasserin |4 aut | |
| 700 | 1 | |a Winton, Elliott |e verfasserin |4 aut | |
| 700 | 1 | |a O'Connell, Casey |e verfasserin |4 aut | |
| 700 | 1 | |a Goel, Swati |e verfasserin |4 aut | |
| 700 | 1 | |a Oh, Stephen T |e verfasserin |4 aut | |
| 700 | 1 | |a Schiller, Gary |e verfasserin |4 aut | |
| 700 | 1 | |a McCloskey, James |e verfasserin |4 aut | |
| 700 | 1 | |a Palmer, Jeanne |e verfasserin |4 aut | |
| 700 | 1 | |a Holmes, Houston |e verfasserin |4 aut | |
| 700 | 1 | |a Hager, Steven |e verfasserin |4 aut | |
| 700 | 1 | |a Assad, Albert |e verfasserin |4 aut | |
| 700 | 1 | |a Erickson-Viitanen, Susan |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Daver, Naval |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Blood advances |d 2016 |g 8(2024), 6 vom: 26. März, Seite 1515-1528 |w (DE-627)NLM268683263 |x 2473-9537 |7 nnns |
| 773 | 1 | 8 | |g volume:8 |g year:2024 |g number:6 |g day:26 |g month:03 |g pages:1515-1528 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1182/bloodadvances.2023011620 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 8 |j 2024 |e 6 |b 26 |c 03 |h 1515-1528 | ||