Comparing the safety and efficacy of ruxolitinib in patients with Dynamic International Prognostic Scoring System low-, intermediate-1-, intermediate-2-, and high-risk myelofibrosis in JUMP, a Phase 3b, expanded-access study
- PMID: 34224180
- PMCID: PMC8518822
- DOI: 10.1002/hon.2898
Comparing the safety and efficacy of ruxolitinib in patients with Dynamic International Prognostic Scoring System low-, intermediate-1-, intermediate-2-, and high-risk myelofibrosis in JUMP, a Phase 3b, expanded-access study
Abstract
Ruxolitinib, a potent Janus kinase 1/2 inhibitor, has demonstrated durable improvements in patients with myelofibrosis. In this analysis of the Phase 3b JUMP study, which included patients aged ≥18 years with a diagnosis of primary or secondary myelofibrosis, we assessed the safety and efficacy of ruxolitinib in patients stratified by Dynamic International Prognostic Scoring System (DIPSS) risk categories. Baseline characteristic data were available to assess DIPSS status for 1844 of the 2233 enrolled patients; 60, 835, 755, and 194 in the low-, intermediate (Int)-1-, Int-2-, and high-risk groups, respectively. Ruxolitinib was generally well tolerated across all risk groups, with an adverse-event (AE) profile consistent with previous reports. The most common hematologic AEs were thrombocytopenia and anemia, with highest rates of Grade ≥3 events in high-risk patients. Approximately, 73% of patients experienced ≥50% reductions in palpable spleen length at any point in the ≤24-month treatment period, with highest rates in lower-risk categories (low, 82.1%; Int-1, 79.3%; Int-2, 67.1%; high risk, 61.6%). Median time to spleen length reduction was 5.1 weeks and was shortest in lower-risk patients. Across measures, 40%-57% of patients showed clinically meaningful symptom improvements, which were observed from 4 weeks after treatment initiation and maintained throughout the study. Overall survival (OS) was 92% at Week 72 and 75% at Week 240 (4.6 years). Median OS was longer for Int-2-risk than high-risk patients (253.6 vs. 147.3 weeks), but not evaluable in low-/Int-1-risk patients. By Week 240, progression-free survival (PFS) and leukemia-free survival (LFS) rates were higher in lower-risk patients (PFS: low, 90%; Int-1, 82%; Int-2, 46%; high risk, 15%; LFS: low, 92%; Int-1, 86%; Int-2, 58%; high risk, 19%). Clinical benefit was seen across risk groups, with more rapid improvements in lower risk patients. Overall, this analysis indicates that ruxolitinib benefits lower-risk DIPSS patients in addition to higher risk.
Keywords: Dynamic International Prognostic Scoring System; efficacy; ruxolitinib; safety.
© 2021 The Authors. Hematological Oncology published by John Wiley & Sons Ltd.
Conflict of interest statement
Francesco Passamonti has received research funding from and served on speaker bureaus for Celgene and Novartis. Vikas Gupta has received consultancy fees, honoraria, and research funding from Novartis and has received consultancy fees and research funding from Incyte. Lynda Foltz has received consultancy fees from Pfizer; research funding from Gilead, Incyte, and Promedior; and consultancy fees, honoraria, and research funding from Celgene and Novartis. Andrey Zaritskey has received consultancy fees from Janssen and Novartis and has served on speaker bureaus for Novartis. Haifa Kathrin Al‐Ali has received consultancy fees, honoraria, and research funding from Celgene and Novartis; honoraria from Alexion; and consultancy fees and honoraria from Gilead. Renato Tavares has received consultancy fees from Novartis. Pia Raanani has received grants from Ariad (Medison), Novartis, and Pfizer and has received consultancy fees from and has served on advisory boards for Ariad (Medison), Bristol‐Myers Squibb, Novartis, and Pfizer. Martin Griesshammer has received consultancy fees and honoraria from and has served on speaker bureaus for AOP Orphan, Baxalta, Gilead, Novartis, and Shire and has received honoraria from and has served on speaker bureaus for Sanofi. Catherine Bouard, Carole Paley, and Ranja Tiwari are employees of Novartis. Alessandro M. Vannuchi has served on speaker bureaus for Gilead and Shire and has served on the board of directors or advisory committees for, has received research funding from, and has served on speaker bureaus for Novartis. The other authors declare that there are no conflict of interests.
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