ASH 2021 - Myelofibrosis

Safe and effective therapeutic options are needed in patients with advanced myelofibrosis and high-risk mutations. Bomedemstat demonstrated improvements in symptoms and spleen responses in patients previously treated with ruxolitinib.

TGFβ is a cytokine that enhances myelofibrosis disease progression. AVID200, a TGFβ1/3 inhibitor, may provide clinical benefit manifesting as improved platelet counts in patients with myelofibrosis who have thrombocytopenia.

JAK inhibitors are approved in myelofibrosis for relief of symptoms and improvement in spleen responses but have not been shown to impact disease progression. Tagraxofusp monotherapy holds promise for treating myelofibrosis patients who are refractory to JAK inhibitors based on early clinical data.

Thrombus formation in patients with myelofibrosis is a common marker of disease progression. The relationship between IPSS score and JAK mutation status may distinguish patients at high risk for thrombosis, which may serve as a guide to therapy decisions.

Patients with essential thrombocythemia and myelofibrosis enroll in various studies in both academic and community centers across the United States. The comparison of patient characteristics across these centers may provide valuable insight into the management of these myeloproliferative neoplasms.

Conditioning regimens for allo-HSCT includes either myeloablative conditioning or reduced-intensity conditioning. The use of fludarabine/busulfan appears to deliver better patient outcomes after transplant compared with other commonly used conditioning regimens.

Clinical trials have demonstrated JAK2 inhibition with fedratinib effectively reduces spleen volume and improves symptoms in patients with myelofibrosis. It has yet to be determined whether spleen size before fedratinib therapy influences these effects.

Low-dose ruxolitinib is an approved therapy for patients with myelofibrosis who have thrombocytopenia, but efficacy may be limited. Evidence from PERSIST-2 indicate pacritinib at full dose may provide additional clinical benefit with a similar safety profile compared with ruxolitinib.

Pacritinib is currently under investigation in multiple trials and demonstrated efficacy and safety in patients with advanced myelofibrosis during the study period. Patients who continue pacritinib on a compassionate-use basis show further improvement in clinical outcomes.

Patients with myelofibrosis who are refractory to JAK inhibitors often lack effective treatment options that not only manage symptoms but can also reduce disease progression. Navtemadlin may improve disease burden in these patients through disease modification.