Methodological challenges in the development of endpoints for myelofibrosis clinical trials

Lancet Haematol. 2024 May;11(5):e383-e389. doi: 10.1016/S2352-3026(24)00067-X. Epub 2024 Apr 8.

Abstract

Myelofibrosis is a myeloid neoplasm characterised by the presence of JAK2, CALR, or MPL mutations (with a 90% mutation frequency) and trilineage myeloid proliferation with prominent megakaryocyte atypia. People with myelofibrosis have a lower survival rate and poorer quality of life than healthy individuals. Therapy for myelofibrosis uses Janus kinase inhibitors, which reduce splenomegaly and alleviate symptoms. Regulatory approvals for Janus kinase inhibitors have focused on this dual endpoint. In this Viewpoint, we discuss the validity of using spleen reduction as a surrogate endpoint for the disease-modifying activity of candidate drugs for myelofibrosis. We suggest alternative endpoints addressing unmet patient needs, including progression-free survival and overall survival. Moreover, we highlight the importance of selecting a core set of crucial outcomes with which we can individualise clinical decision making and standardise reporting of clinical trials results. We propose selecting patient-reported outcomes and anaemia response. We also suggest integrating economic considerations in the process of evaluating new drugs for myelofibrosis.

MeSH terms

  • Clinical Trials as Topic*
  • Endpoint Determination
  • Humans
  • Janus Kinase Inhibitors / therapeutic use
  • Primary Myelofibrosis* / drug therapy
  • Quality of Life

Substances

  • Janus Kinase Inhibitors