Unmet Clinical Needs in Myelofibrosis

Srdan Verstovsek, MD, PhD, a professor of Medicine and a hematologic oncologist at the University of Texas MD Anderson Cancer Center, discusses unmet clinical needs in myelofibrosis.

According to Verstovsek, not every patient with myelofibrosis needs intervention from day one. At prognostication, care providers should determine if the patient is transplant eligible. The 3 main hallmark of interventions include anemia, symptomatic splenomegaly, and general systemic symptoms. These can manifest as night sweats, low grade fevers, itching, bone, exit pains, fatigue, weakness, and weight loss.

Currently, ruxolitinib (Jakafi) and fedratinib (Inrebic) are the 2 JAK inhibitors approved for this patient population. Both are anti-inflammatory and anti-proliferative. However, the effects of the agents only last for an average of 3 years. Anemia remains a problem for this population, yet no anemia drug is approved this this patient population. Fedratinib can also be used as a second-line agent, but only in a minority of patients. 

0:08 | Myelofibrosis patients have 3 hallmarks that require intervention. Remember, not everybody actually needs therapy from day one. We look at the prognosis, which is the one that will determine where the patient has bad enough disease to intervene with a transplant. That's one part of it. Then once you're done with prognostication, you say, 'is there something that bothers the patient that I need to correct? And the 3 main reasons are anemia, symptomatic splenomegaly, and general systemic symptoms. Night sweating, low grade fevers, itching, bone exit pains, fatigue, weakness, weight loss. So, three areas of concern. And currently, we have ruxolitinib and fedratinib, JAK inhibitors approved as a therapy for patients that have platelets about 50 and required control of the spleen and symptoms. This is what they're good for. They're anti-proliferative, and to degree, anti-inflammatory agents. So, the quality of life improves, the spleen becomes smaller, but it doesn't last forever. It lasts an average of 3 years. We know that they worsen the anemia, so anemia is a problem. Our guidance would say to add anemia drugs to JAK inhibitors, but we don't have any approved, so we scramble and use some off-label drugs for it. You can use one JAK inhibitor after the other. In NCCN guidelines, fedratinib is listed as a second line choice. But it's applicable only to a minority of the patients because most people also have anemia and thrombocytopenia in the course of the therapy. So, we are limited to JAK inhibitors, 2 of them for a large group of people in frontline setting for a limited duration, unfortunately. And we don't tackle anemia at all. So, a lot of issues here that we need to develop new drugs for.