The survival benefit derived from ruxolitinib, as well as its ability to impact spleen volume and reduce symptoms, have made it the cornerstone of drug therapy in myelofibrosis, according to a recent review. In addition to its approval for second-line therapy of polycythemia vera, ruxolitinib is being developed for essential thrombocythemia. Still, unmet needs remain, prompting investigators to explore options that build on ruxolitinib’s success.

These include inhibitors of histone deacetylases and DNA methyltransferases, phosphatidylinositol-3-kinase isoforms, heat shock protein 90, cyclin-dependent kinases 4/6, and Hedgehog signaling, among others. Additionally, first-in-class agents such as the activin receptor IIA ligand trap sotatercept (for anemia of myelofibrosis), the telomerase inhibitor imetelstat, and the antifibrotic agent PRM-151 (recombinant human pentraxin-2) are also in clinical trials.