Novel Janus-kinase (JAK) Inhibitors in Myelofibrosis

ABSTRACTIntroduction JAK inhibitors (JAKis), used in the treatment of myelofibrosis, have entered standard treatment, providing significant improvements in spleen size and symptom burden. Although splenomegaly provides a reduction and some improvement in cytopenia, there is still a way to go. Novel JAKis are being investigated to overcome barriers to treatment access, such as therapeutic challenges, intolerance, and unresponsiveness.Areas covered This review includes the current status of JAKi treatment for myelofibrosis, mainly focusing on investigational JAKis; jaktinib, lestaurtinib, itacitinib, gandotinib, BMS-911543, ilginatinib, TQ05105, and flonoltinib maleate. MEDLINE and clinicaltrials.gov were screened to identify all completed or active studies on this topic. The outcomes of the preclinical studies and clinical trials are presented and discussed for each drug.Expert opinion In patients with myelofibrosis, momelotinib was effective in treating anemia, whereas jaktinib was effective in both anemia and Total Symptom Score (TSS). More phase 3 studies are needed to provide more precise evidence. The increasing variety of JAKis will allow for more personalized treatment options for myelofibrosis in the future. The potential impact on disease progression, molecular responses, and the duration of this response will become important parameters for future evaluations of these drugs.KEYWORDS: BMS-911543flonoltinib maleategandotinibitacitinibilginatinibJAK inhibitorslestaurtinibmomelotinib Article highlights Momelotinib and jaktinib are effective in anemic patients with myelofibrosis.For patients with constitutional symptoms, jaktinib and JAK1-selective itacitinib are considerable drug candidates.Itacitinib provides improvements with less myelosuppression owing to its selectivity for JAK1.Declaration of interestAEE has received advisory board and speaker bureau honoraria from Novartis and Bristol-Myers Squibb. All other authors have no conflict of interest to declare.Reviewer disclosuresA reviewer on this manuscript has disclosed research funding from Incyte, CTI and BMS, and honoraria and consulting fees from Incyte, CTI, BMS and GSK. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.Additional informationFundingThis paper was not funded.