Meaningful symptomatic change in patients with myelofibrosis from the SIMPLIFY studies.

Patients with myelofibrosis (MF) develop symptoms due to bone marrow fibrosis, systemic inflammation, and/or organomegaly. Alleviating symptoms improves overall quality of life. Clinical trials have historically defined symptom response as a reduction of at least 50% in Total Symptom Score at week 24 compared with baseline. Whether 50% constitutes a meaningful benefit has not been established. This study determined the meaningful change threshold (MCT) for two momelotinib phase III trials, SIMPLIFY-1 and SIMPLIFY-2. The absolute and percentage MCT was determined using anchor-based methods applied to the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) v2.0 and Patient Global Impression of Change. MCTs were applied retrospectively to determine responder rates. Generalized estimating equations estimated the treatment-related difference in likelihood of improvement. In SIMPLIFY-1, a Janus kinase (JAK) inhibitor-naïve population, the MCT was 8 points. In SIMPLIFY-2, a previously JAK inhibitor-treated population, the MCT was 6 points. A 32% MCT was determined in both studies, showing that the historic 50% reduction threshold may be a conservative choice. In SIMPLIFY-1, a similar proportion of patients achieved responder status with 24 weeks of momelotinib or ruxolitinib therapy based on the absolute MCT (39% vs. 41%, respectively). In SIMPLIFY-2, a significantly greater proportion of patients treated with momelotinib achieved responder states compared with best available therapy based on absolute and percent change MCTs. This study demonstrates that momelotinib provided clinically meaningful symptom benefit for patients with MF and provides insight into the appropriateness of the symptom change threshold used in historical studies.

Informations de copyright

Copyright © 2024 International Society for Pharmacoeconomics and Outcomes Research, Inc. Published by Elsevier Inc. All rights reserved.