Abstract
<h2>Introduction</h2> The field of myeloproliferative neoplasms (MPN) has entered a new, exciting era since the clinical development and FDA-approval of the JAK1/2 inhibitor ruxolitinib in 2011 and the JAK2 inhibitor fedratinib in 2019 for treatment of myelofibrosis (MF), the most aggressive MPN. Notwithstanding the unprecedented clinical benefits, including transformative improvement in quality-of-life that the approved JAK inhibitors have elicited in MF patients and their widespread use, a tenacious quest for novel MF treatment strategies has been pursued. Research endeavors have focused on developing new monotherapies and rational combination treatments that exhibit complementary activity or act synergistically with ruxolitinib.<sup>1,2</sup> The new regimens in clinical development are aimed at addressing major unmet medical needs, such as anemia and thrombocytopenia, progression of MF to acute myeloid leukemia, suboptimal response or resistance to ruxolitinib,<sup>3</sup> and the short overall survivals associated with the former settings.<sup>4,5</sup> The novel investigational agents may target alternate biological pathways besides JAK/STAT and/or enhance the efficacy of ruxolitinib. In this abstract, we have highlighted select, promising investigational agents that are currently evaluated in pivotal phase 3 clinical trials for MF (Table 1).
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