Challenges of Treating Patients With Cytopenias in Myelofibrosis

Srdan Verstovsek, MD, PhD, professor of medicine and hematologic oncologist at the University of Texas MD Anderson Cancer Center, discusses the issues faced by patients with cytopenic myelofibrosis.

The main cytopenias of concern for patients with myelofibrosis are low red blood cell count, also known as anemia, and low platelet count, or thrombocytopenia. According to Verstovsek, patients with a hemoglobin level of less than 10 g/dL are considered anemic, and patients whose hemoglobin is less than 8 g/dL require blood transfusions. Some are transfusion-dependent and cannot survive without transfusions given at a rate of 2 units monthly for at least 3 months.

Patients are considered to have thrombocytopenia if their platelet count is below 100 × 109/L, and severely thrombocytopenic if their platelet count is below 50 × 109/L. Verstovsek says it is common for patients with myelofibrosis to experience both anemia and thrombocytopenia together.

Previously approved therapies, including ruxolitinib (Jakafi) and fedratinib (Inrebic), are not well tolerated in cytopenic patients, and other therapies such as steroids are not always effective. These challenges led to the development of pacritinib (Vonjo), which was approved for patients with severe thrombocytopenia, and momelotinib, which showed improvements in patients with anemia and is pending FDA approval.

TRANSCRIPTION:

0:08 | When we say cytopenic myelofibrosis patients, we are usually talking about people who are anemic or thrombocytopenic to a certain degree. They may have 1 or the other, or both. Many times, cytopenia means both low red blood cells and the low platelets. Hemoglobin less than 10 [g/dL] is a typical definition of an anemic patient, but of course, there are patients that require blood transfusion, so transfusion-requiring patients. This is typically with hemoglobin less than 8 [g/dL] or transfusion-dependent patients, and they live off of blood that is given to them. Typically, we talk about 2 units monthly for 2 months, or 3 months. That would be a definition of transfusion-dependent patients. With thrombocytopenia, we usually say thrombocytopenic patients [are] the ones with platelets below 100 [× 109/L]. Below 50 [× 109/L], would be severely thrombocytopenic. Again, these live together in, usually, the same person, anemia, and thrombocytopenia.

1:06 | If we talk about cytopenic patients, they're [at a] disadvantage, because we don't have good therapy to give them. The ruxolitinib, for example, that has been 10 years in the making now. [It] has to be adjusted for platelet numbers and many [physicians] adjust in [patients] who are anemic. So… we are using [them] but [are] not satisfied with the current practice ruxolitinib and fedratinib. There is certainly an area of unmet need. We may use something that we call best-value therapy, steroids, anabolic steroids, lenalidomide, thalidomide, in combination, perhaps with prednisone to counteract low counts, but that doesn't really work often. If it works, it doesn't work for too long. Between the low doses or into different use of current JAK inhibitors and unsatisfactory efficacy of best available therapy that has been around off-label use of other medications, we don't have good therapies here for these patients.