The latest clinical research findings about novel agents and evolving treatment strategies in myelofibrosis (MF) were presented at the 2022 American Society of Hematology (ASH) 64th Annual Meeting and summarized in an article published in the Journal of Hematology & Oncology

The article focused on next-generation Janus kinase (JAK) inhibitors that are newly approved by the US Food and Drug Administration (FDA) to treat patients with MF that is refractory to ruxolitinib treatment or patients who cannot tolerate ruxolitinib, as well as other non-JAK inhibitor therapies including epigenetic modifiers and inhibitors of the apoptotic machinery and intracellular signaling pathways that are currently being investigated in clinical trials.

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“The future of MF management is bright and promising,” the authors of the study concluded.

They focused on data showing how momelotinib reduced symptoms and spleen volume in patients with MF, improved transfusion independence, and prolonged the survival of patients who failed treatment with another JAK inhibitor.

They also reported on patients with MF who were treated with another recently approved JAK inhibitor, pacritinib, who achieved greater transfusion independence than those treated with best-available therapy. In addition, they discussed the effects of TP-3654, a selective oral proto-oncogene serine/threonine-protein kinase 1 inhibitor that showed signs of clinical activity in a phase 1/2 clinical trial, reduced spleen volume, improved disease symptoms, and reduced cytokine levels in patients who were previously treated with a JAK inhibitor. 

Finally, they reported the effects of IMG-7289, a lysine-specific demethylase-1 inhibitor, in reducing symptoms, spleen volume, and bone marrow fibrosis in a phase 2 clinical trial.

The article also contained information about frontline “add-on” targeted therapeutics that are used in combination with ruxolitinib, including the human double minute-2 inhibitor, siremadlin; the selective bromodomain and extraterminal inhibitor, pelabresib; navitoclax, which inhibits the anti-apoptotic BCL-2 family proteins; parsaclisib, a potent and highly selective PI3 kinase inhibitor; and selinexor, which inhibits exportin-1.

This year’s ASH Annual Meeting will take place from December 9 to 12, 2023 in San Diego, California.

Reference

Wang A, Liu J, Pu JJ. Novel agents and evolving strategies in myelofibrotive neoplasm: an update from 2022 ASH annual conference. J Hematol Oncol. 2023;16(1):53. doi:10.1186/s13045-023-01446-0