New Concepts of Treatment for Patients with Myelofibrosis

Opinion statementSeven years after the approval of the Janus kinase 1/2 (JAK1/2) inhibitor ruxolitinib, it remains the only drug licensed for the treatment of myelofibrosis. Patients who discontinue ruxolitinib have a dismal outcome, and this is, therefore, an area of significant unmet need. Given the central role that JAK-signal transducer and activator of transcription (STAT) activation plays in disease pathogenesis, there have been many other JAK inhibitors tested, but most have been abandoned, for a variety of reasons. The JAK2-selective inhibitor fedratinib has recently been resurrected, and there has been a resurgence of interest in the failed JAK1/2 inhibitor momelotinib, which possibly improves anemia. Pacritinib, a non-myelosuppressive JAK2-selective inhibitor, is currently in a dose-ranging study mandated by regulatory authorities. A plethora of other targeted agents, most backed by preclinical data, are in various stages of investigation. These include epigenetic and immune therapies, agents targeting cellular survival, metabolic and apoptotic pathways, the cell cycle, DNA repair, and protein folding and degradation, among others. However, at this time, none of these is close to registration or even in a pivotal trial, illustrating the difficulties in recapitulating the clinical disease in preclinical models. Most current clinical trials are testing the addition of a novel agent to ruxolitinib, either in the frontline setting or in the context of an insufficient re...
Source: Current Treatment Options in Oncology - Category: Cancer & Oncology Source Type: research