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Non\u2010transplant treatment options in MF are palliative in scope and include Janus kinase 2 (JAK2) inhibitors (JAKi): momelotinib (FDA approved on September 15, 2023), ruxolitinib (November 16, 2011), fedratinib (August 16, 2019), and pacritinib (February 28, 2022); all four JAKi are effective in reducing spleen size and alleviating symptoms, considered a drug class effect and attributed to their canonical JAK\u2013STAT inhibitory mechanism of action. In addition, momelotinib exhibits erythropoietic effect, attributed to alleviation of ineffective erythropoiesis through inhibition of activin A receptor type\u2010I (ACVR1). In transplant\u2010ineligible or deferred patients, the order of treatment preference is based on specific symptoms and individual assessment of risk tolerance. Because of drug\u2010induced immunosuppression and other toxicities attributed to JAKi, we prefer non\u2010JAKi drugs as initial treatment for MF\u2010associated anemia that is not accompanied by treatment\u2010requiring splenomegaly or constitutional symptoms. Otherwise, it is reasonable to consider momelotinib as the first\u2010line JAKi treatment of choice, in order to target the triad of quality\u2010of\u2010life offenders in MF: anemia, splenomegaly, and constitutional symptoms\/cachexia. For second\u2010line therapy, we favor ruxolitinib, over fedratinib, based on toxicity profile. Pacritinib and fedratinib provide alternative options in the presence of severe thrombocytopenia or ruxolitinib\u2010resistance\/intolerance, respectively. Splenectomy remains a viable option for drug\u2010resistant symptomatic splenomegaly and cytopenia.<\/jats:p>","DOI":"10.1002\/ajh.27163","type":"journal-article","created":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T16:31:49Z","timestamp":1704213109000},"page":"300-308","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Momelotinib expands the therapeutic armamentarium for myelofibrosis: Impact on hierarchy of treatment choices"],"prefix":"10.1002","volume":"99","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-3821","authenticated-orcid":false,"given":"Ayalew","family":"Tefferi","sequence":"first","affiliation":[{"name":"Division of Hematology, Department of Medicine Mayo Clinic  Rochester Minnesota 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