Investigational non-JAK inhibitors for chronic phase myelofibrosis.

This article reviews the efficacy data from completed and ongoing early phase clinical trials of non-JAKi agents for chronic phase MF. The article also illuminates some of the challenges of myelofibrosis drug development.Expert opinion: Most non-JAKi agents tested so far have shown modest benefit in improving the efficacy of ruxolitinib. Several novel agents such as BET inhibitor- CPI-0610, activin receptor ligand trap- luspatercept, recombinant pentraxin-PRM-151, telomerase inhibitor- imetelstat and navitoclax, have shown promising activity; however, they require vigorous evaluation in randomized controlled trials to understand the clinical benefit. Drugs that target new molecular pathways (MDM2, p-selectin, TIM-3, Bcl-2, TGF-β, aurora kinase) and immune-based strategies (CALR vaccine, anti-PD-1, allogeneic cord blood regulatory T cells) are in early phase trials. Further translational studies to target leukemic stem cells, improvement in trial designs by incorporating control arm and survival endpoints, and patient-focused collaborations among all stakeholders could pave a way for future success in MF drug development. PMID: 32245330 [PubMed - as supplied by publisher]
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Tags: Expert Opin Investig Drugs Source Type: research