Dr. Synder on the Quest to Revolutionize Management of Myelofibrosis

David S. Snyder, MD, associate chair, Department of Hematology and Hematopoietic Cell Transplantation, professor, Hematology and Hematopoietic Cell Transplantation, and hematologist/oncologist, City of Hope, discusses ongoing research dedicated to providing more curative options to patients with myelofibrosis.

Prior to the approval of the JAK2 inhibitor fedratinib (Inrebic), ruxolitinib (Jakafi) was the only available drug with the ability to target key clinical features of myelofibrosis, such as splenomegaly and constitutional symptoms. Despite its benefits, not all patients are able to tolerate the agent due to its associated toxicities, like thrombocytopenia.

Fedratinib, a drug that attacks the JAK2 protein in two places rather than one, not only offers an additional option to patients, but may prove to be more effective than ruxolitinib. JAK inhibitors alone have not been successful in changing the biology of myelofibrosis; however, combination approaches are under investigation.

Investigators have been channeling all of their efforts into developing a drug or combination of agents that will take the place of transplantation in the space, says Snyder, a shift comparable to that seen in chronic myeloid leukemia, where the emergence of imatinib (Gleevec) and other TKIs have revolutionized the management of the disease. With these novel agents, stem cell transplants are rarely in these patients. However, because myelofibrosis is more complex than CML, this will be a difficult task to accomplish, says Snyder, and as such, transplantation will likely remain the only curative option in the coming years.