Pacritinib response is associated with overall survival in myelofibrosis: PERSIST-2 landmark analysis of survival Journal Article

   

Authors:	Ajufo, H.; Bewersdorf, J. P.; Harrison, C.; Palandri, F.; Mascarenhas, J.; Palmer, J.; Gerds, A.; Kiladjian, J. J.; Buckley, S.; Derkach, A.; Roman-Torres, K.; Rampal, R. K.
Article Title:	Pacritinib response is associated with overall survival in myelofibrosis: PERSIST-2 landmark analysis of survival
Abstract:	Spleen volume reduction (SVR) is a key endpoint in inhibitors of Janus kinase (JAK) inhibitor studies. Retrospective analyses have demonstrated an association between SVR and improved overall survival (OS) among patients treated with ruxolitinib with a platelet count > 100 × 109/L. Whether this association occurs in patients with thrombocytopenia is unclear. Pacritinib, a JAK2/IRAK1/ACVR1 inhibitor, demonstrated improved SVR versus best available therapy (BAT [best available therapy]; including ruxolitinib) in patients with myelofibrosis and platelet counts ≤ 100 × 109/L in the PERSIST-2 study. Patients on study at the start of the 12-week SVR window on pacritinib 200 mg twice daily or BAT were included. OS was evaluated among SVR responders versus non-responders using different SVR thresholds (≥ 35%, ≥ 20%, ≥ 10%, and > 0%). Among patients on pacritinib (n = 89), SVR ≥ 10% demonstrated the greatest separation in OS curves between responders and non-responders (HR, 0.00; 95% CI, 0.00–0.14; p < 0.01), though SVR ≥ 0% and SVR ≥ 20% were also associated with improved OS. No SVR threshold conferred OS benefit on BAT (n = 84), including ruxolitinib (n = 39). In patients with myelofibrosis and platelets ≤ 100 × 109/L, achieving SVR on pacritinib, but not BAT (including ruxolitinib), was associated with significant OS benefit, suggesting that pacritinib may offer a unique survival advantage in patients with myelofibrosis and thrombocytopenia who achieve any SVR. Trial Registration: ClinicalTrials.gov number: NCT02055781. © 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.
Keywords:	adult; cancer survival; controlled study; treatment outcome; treatment response; aged; aged, 80 and over; middle aged; survival analysis; myelofibrosis; survival rate; major clinical study; overall survival; clinical trial; mortality; myeloid metaplasia; primary myelofibrosis; protein kinase inhibitor; randomized controlled trial; thrombocytopenia; pyrimidines; protein kinase inhibitors; janus kinase; pyrazole derivative; multicenter study; pyrazoles; diagnosis; phase 3 clinical trial; drug therapy; pyrimidine derivative; erythrocyte transfusion; nitriles; nitrile; platelet count; etiology; janus kinase 2 inhibitor; spleen size; bridged compound; pacritinib; ruxolitinib; spleen volume; very elderly; humans; human; male; female; article; bridged-ring compounds; 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene; total symptom score
Journal Title:	European Journal of Haematology
Volume:	114
Issue:	2
ISSN:	0902-4441
Publisher:	John Wiley & Sons
Date Published:	2025-02-01
Start Page:	238
End Page:	247
Language:	English
DOI:	10.1111/ejh.14321
PUBMED:	39400386
PROVIDER:	scopus
PMCID:	PMC11707811
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85206126217&doi=10.1111%2fejh.14321&partnerID=40&md5=5853bf2f84eea1b411bc0df61065b54d
Notes:	Article -- Source: Scopus

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