The pharmacotherapeutic management of patients with myelofibrosis: looking beyond JAK inhibitors

Introduction: The approach to myelofibrosis (MF) has been revolutionized in recent years, overcoming the traditional therapies, often not very effective. Janus kinase inhibitors (JAKi - from ruxolitinib up to momelotinib) were the first class of drugs with considerable results. Areas covered: Ongoing, new molecules are being tested that promise to give hope even to those patients not eligible for bone marrow transplants who become intolerant or are refractory to JAKi, for which therapeutic hopes are currently limited. Telomerase, murine double minute 2 (MDM2), phosphatidylinositol 3-kinase δ (PI3Kδ), BCL-2/xL, and bromodomain and extra-terminal motif (BET) inhibitors are the drugs with promising results in clinical trials and close to closure with consequent placing on the market, finally allowing JAK to look beyond. The novelty of the MF field was searched in the PubMed database, and the recently completed/ongoing trials are extrapolated from the ClinicalTrial website. Expert opinion: From this point of view, the use of new molecules widely described in this review, probably in association with JAKi, will represent the future treatment of choice in MF, leaving, in any case, the potential new approaches actually in an early stage of development, such as the use of immunotherapy in targeting CALR, which is coming soon.