Myelofibrosis

Abstract

The clinical phenotype of primary and post-polycythemia vera and postessential thrombocythemia myelofibrosis (MF) is dominated by splenomegaly, symptomatology, a variety of blood cell alterations, and a tendency to develop vascular complications and blast phase. Diagnosis requires assessing complete cell blood counts, bone marrow morphology, deep genetic evaluations, and disease history. Driver molecular events consist of JAK2V617F, CALR, and MPL mutations, whereas about 8% to 10% of MF are "triple-negative." Additional myeloid-gene variants are described in roughly 80% of patients. Currently available clinical-based and integrated clinical/molecular-based scoring systems predict the survival of patients with MF and are applied for conventional treatment decision-making, indication to stem cell transplant (SCT) and allocation in clinical trials. Standard treatment consists of anemia-oriented therapies, hydroxyurea, and JAK inhibitors such as ruxolitinib, fedratinib, and pacritinib. Overall, spleen volume reduction of 35% or greater at week 24 can be achieved by 42% of ruxolitinib-, 47% of fedratinib-, 19% of pacritinib-, and 27% of momelotinib-treated patients. Now, it is time to move towards new paradigms for evaluating efficacy like disease modification, that we intend as a robust and unequivocal effect on disease biology and/or on patient survival. The growing number of clinical trials potentially pave the way for new strategies in patients with MF. Translational studies of some molecules showed an early effect on bone marrow fibrosis and on variant allele frequencies of myeloid genes. SCT is still the only curative option, however, it is associated with relevant challenges. This review focuses on the diagnosis, prognostication, and treatment of MF.

Graphical abstract

Figure 1.

Current management of MF. This algorithm represents our approach to the management of MF with some considerations on COVID-19, SCT selection, anemia-oriented treatments, and risk-based strategy to control clinical needs of patients. CBC, complete blood count; CI, cormorbidity index; Dan, danazol; del, deletion; EPO, erythropoietin; ESAs, erythropoiesis stimulating agents; FEDR, fedratinib; HU, hydroxyurea; JAKis, JAK inhibitors; Len, lenalidomide; MF, myelofibrosis; MonoAb, monoclonal antibody; MTD, maximum tolerated dose; PAC, pacritinib; PEG-IFN, PEGylated-interferon; PLT, platelets; PS, performance status; RBC, red blood cells; RUX, ruxolitinib; SCT, stem cells transplant; Thal, thalidomide; tx, treatment. ¹As for DIPSS/apex (Dynamic International Prognostic Scoring System) or MIPSS-70/apexV2 (Mutation-Enhanced International Prognostic Scoring System) or MYSEC-PM (Myelofibrosis Secondary to polycythemia vera and essential thrombocythemia-Prognostic Model. ²Low, intermediate and selected high-risk MTSS (Myelofibrosis Transplant Scoring System) cases.