Meaningful symptomatic change in patients with myelofibrosis from the SIMPLIFY studies

Stacie Hudgens*, Srdan Verstovsek, Lysbeth Floden, Claire N. Harrison, Jeanne Palmer, Vikas Gupta, Donal McLornan, Mary Frances McMullin, Jean Jacques Kiladjian, Lynda Foltz, Uwe Platzbecker, Maria Laura Fox, Adam J. Mead, David M. Ross, Stephen T. Oh, Andrew A. Perkins, Michael F. Leahy, Samineh Deheshi, Rafe Donahue, Barbara J. KlenckeRuben A. Mesa

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Objectives: Patients with myelofibrosis 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 2 momelotinib phase III trials, SIMPLIFY-1 and SIMPLIFY-2. 

Methods: The absolute and percentage MCT was determined using anchor-based methods applied to the modified Myeloproliferative Neoplasm Symptom Assessment Form 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. 

Results: In SIMPLIFY-1, a Janus kinase inhibitor-naive population, the MCT was 8 points. In SIMPLIFY-2, a previously Janus kinase 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. 

Conclusions: This study demonstrates that momelotinib provided clinically meaningful symptom benefit for patients with myelofibrosis and provides insight into the appropriateness of the symptom change threshold used in historical studies.

Original languageEnglish
JournalValue in Health
Early online date02 Feb 2024
DOIs
Publication statusEarly online date - 02 Feb 2024

Bibliographical note

Funding Information:
This study was funded by Sierra Oncology, a GSK company. Writing support was provided by Second City Science and Jarin Chu, PharmD, PhD (Nucleus Global, an Inizio Company), in accordance with the International Committee of Medical Journal Editors and Good Publication Practice guidelines and was supported by GSK. The authors also thank the patients and families who participated in the trial and all study investigators and site staff.

Publisher Copyright:
© 2024 International Society for Pharmacoeconomics and Outcomes Research, Inc.

Keywords

  • Janus kinase inhibitor
  • meaningful change threshold
  • momelotinib
  • myelofibrosis

ASJC Scopus subject areas

  • Health Policy
  • Public Health, Environmental and Occupational Health

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