Fedratinib in patients with myelofibrosis previously treated with ruxolitinib: An updated analysis of the JAKARTA2 study using stringent criteria for ruxolitinib failure
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Open Access
- 1 June 2020
- journal article
- research article
- Published by Wiley in American Journal of Hematology
- Vol. 95 (6), 594-603
- https://doi.org/10.1002/ajh.25777
Abstract
Fedratinib is an oral, selective Janus kinase 2 (JAK2) inhibitor. The phase II JAKARTA2 study assessed fedratinib in patients with intermediate- or high-risk myelofibrosis (MF) who were resistant or intolerant to prior ruxolitinib per investigator assessment. Patients received fedratinib 400 mg/day in 28-day cycles. The JAKARTA2 outcomes were initially reported using a last-observation-carried forward (LOCF) analysis in a "Per Protocol" population. This updated analysis of JAKARTA2 employs intention-to-treat analysis principles without LOCF for all treated patients (ITT Population; N = 97), and for a patient subgroup who met more stringent definitions of prior ruxolitinib failure (Stringent Criteria Cohort; n = 79). Median duration of prior ruxolitinib exposure was 10.7 months. The primary endpoint was spleen volume response rate (SVRR; >= 35% spleen volume decrease from baseline to end of cycle 6 [EOC6]). The SVRR was 31% in the ITT Population and 30% in the Stringent Criteria Cohort. Median duration of spleen volume response was not reached. Symptom response rate (>= 50% reduction from baseline to EOC6 in total symptom score [TSS] on the modified Myelofibrosis Symptom Assessment Form [MFSAF]) was 27%. Grade 3-4 anemia and thrombocytopenia rates were 38% and 22%, respectively. Patients with advanced MF substantially pretreated with ruxolitinib attained robust spleen responses and reduced symptom burden with fedratinib.This publication has 38 references indexed in Scilit:
- Optimizing management of ruxolitinib in patients with myelofibrosis: the need for individualized dosingJournal of Hematology & Oncology, 2013
- Effect of Ruxolitinib Therapy on Myelofibrosis-Related Symptoms and Other Patient-Reported Outcomes in COMFORT-I: A Randomized, Double-Blind, Placebo-Controlled TrialJournal of Clinical Oncology, 2013
- A Double-Blind, Placebo-Controlled Trial of Ruxolitinib for MyelofibrosisThe New England Journal of Medicine, 2012
- JAK Inhibition with Ruxolitinib versus Best Available Therapy for MyelofibrosisThe New England Journal of Medicine, 2012
- The Pharmacokinetics, Pharmacodynamics, and Safety of Orally Dosed INCB018424 Phosphate in Healthy VolunteersThe Journal of Clinical Pharmacology, 2011
- Safety and Efficacy of TG101348, a Selective JAK2 Inhibitor, in MyelofibrosisJournal of Clinical Oncology, 2011
- DIPSS Plus: A Refined Dynamic International Prognostic Scoring System for Primary Myelofibrosis That Incorporates Prognostic Information From Karyotype, Platelet Count, and Transfusion StatusJournal of Clinical Oncology, 2011
- What are RBC-transfusion-dependence and -independence?Leukemia Research, 2011
- The Myelofibrosis Symptom Assessment Form (MFSAF): An evidence-based brief inventory to measure quality of life and symptomatic response to treatment in myelofibrosisLeukemia Research, 2009
- Characterization of a Novel C-type Lectin-like Gene, LSECtinJournal of Biological Chemistry, 2004