Investigational non-JAK inhibitors for chronic phase myelofibrosis. (3rd May 2020)

• Record Type: Journal Article
• Authors: Bankar, Aniket; Gupta, Vikas
• Is Part Of: Expert opinion on investigational drugs. Volume 29:Number 5(2020)
• Page Start: 461
• Page End: 474
• Publication Date: 2020-05-03
• Subjects: Myelofibrosis -- non-jak inhibitors -- chronic phase myelofibrosis -- JAK inhibitors -- philadelphia negative myeloproliferative neoplasms -- clinical trial -- investigational drug; Drugs -- Design -- Periodicals; Drugs, Investigational -- Bibliography; Drugs, Investigational -- Periodicals; 615.1
• DOI: 10.1080/13543784.2020.1751121
• Languages: English
• ISSNs: 1354-3784

Abstract

ABSTRACT: Introduction: Patients with myelofibrosis (MF) have no effective treatment option after the failure of approved JAK inhibitor (JAKi) therapy. Non-JAK inhibitors (non-JAKi) that target non-canonical molecular pathways are undergoing clinical evaluations to optimize efficacy and/or to reduce hematological toxicity of JAKi. Area covered: 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 bcl-2 inhibitor- 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, 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.