Work

Calr type 1/like mutation in myelofibrosis is the most prominent predictor of momelotinib drug survival and longevity without transplant

Year: 2024

Type: article

Abstract: Allogeneic hematopoietic stem cell transplant (AHSCT) is at present the only treatment modality in myelofibrosis (MF) that holds the promise of cure or prolongation of life [ 1 ]. Non-transplant treatment options in MF are palliative in scope and include Janus kinase 2 (JAK2) inhibitors (JAKi) [ 2 ]; FDA-approved, in this regard, are ruxolitinib (November 16, 2011), fedratinib (August 16, 2019), pacritinib (February 18, 2022), and most recently momelotinib (September 15, 2023) [ 3 ]. All four FDA-approved JAKi have proven to be variably effective in reducing spleen size and alleviating symptoms. In addition, momelotinib has distinguished itself, from ruxolitinib and fedratinib, by displaying an erythropoietic effect that has been attributed to the drug’s inhibitory activity on activin A receptor type-1 (ACVR1) [ 3 , 4 , 5 ]. Mechanistically, targeting ACVR1 interferes with SMAD signaling and regulation of transcription of genes that contributes to hepcidin expression, ineffective erythropoiesis, and terminal erythroid differentiation [ 6 , 7 ].

Source: Blood Cancer Journal

DOI: 10.1038/s41408-024-01028-4