Dr Gerds on the Importance of Disease-Modifying Therapies in Myelofibrosis

“As it stands right now, in the field of myeloproliferative neoplasms, we have 4 JAK inhibitors that are FDA approved for the treatment of myelofibrosis, but they fall short on disease modification.”

Aaron T. Gerds, MD, MS, an assistant professor in the Department of Medicine at the Case Western Reserve University School of Medicine; the deputy associate director for Clinical Research and a member of the Developmental Therapeutics Program at Case Comprehensive Cancer Center; and a physician in the Department of Hematology and Medical Oncology at Cleveland Clinic, discussed the need for improved disease-modifying therapies for the treatment of patients with myelofibrosis.

Currently, the 4 JAK inhibitors that are FDA approved for the management of this disease occupy much of the focus of the treatment paradigm, Gerds began. However, despite the benefits of these agents, they fall short when achieving true disease modification, he stated. Although JAK inhibitors do modify the disease—making patients’ lives better and allowing them to live longer than if they did not receive the treatment—the agents do not fundamentally reverse the disease state, he explained. Specifically, JAK inhibitors fail to eliminate myelofibrosis cells or reverse the existing scar tissue, he said. Consequently, they do not achieve the ultimate goal of truly bending the survival curve so that it plateaus, he emphasized.

It is vitally important to shift research focus toward therapies that can significantly bend these survival curves and effectively plateau them, Gerds highlighted. The primary clinical aim is the development of treatments that can root out the underlying myelofibrosis, he continued. Once this occurs, all the subsequent benefits, such as improvements in common symptoms, reduction of spleen enlargement, and improvements in anemia, will naturally follow, he reported. The collective goal of future myelofibrosis research is to discover agents that accomplish this systemic eradication of disease, he summarized. Overall, the current efforts—spanning numerous new therapies in both early development and late-stage trials—are focused on how to significantly bend survival curves to a greater extent than what has been accomplished so far with the FDA-approved JAK inhibitors, Gerds concluded.