Janus kinase inhibitor monotherapy and combination therapies for myelofibrosis: what’s the current standard of care?

Introduction: JAK inhibitors (JAKi) have changed the treatment paradigm of myelofibrosis (MF). Currently, 4 JAKis are approved in the US as monotherapy (mono) to treat patients with MF. JAKis are also being studied in combination (combo) with novel agents. Herein, we review some of the key studies that evaluated JAKi as mono and combo in MF. Areas covered: We performed a Pubmed search for ‘JAK inhibitors’ and ‘myelofibrosis’ from 1/2010 to 12/2023. For mono, we included only the unique phase II/III studies of the approved JAKi. Selective studies that evaluated JAKi in combo with the novel agents were also included. Expert opinion: JAKis aim to provide clinical benefit to patients via spleen size reduction and MPN symptom improvement. In order to potentially increase clinical benefit for patients with MF, several novel agents are being partnered with ruxolitinib (RUX) with the ongoing hypothesis to augment greater measures of MF disease modification. The novel agents are either ‘added-on’ to RUX or as a combo in JAKi naïve patients. Also, the mutant-targeting era of therapies is now beginning with novel CALR-mutated, novel JAK2 V617F mutation-specific and type II JAK2i in the initial stages of drug development, representing a new approach to treatment.