PracticeUpdate: Conference Series - EHA 2018

Erythropoietin Treatment More Effective in Myelofibrosis Patients with Anemia and V617F JAK2 Mutations Myelofibrosis patients who develop transfusion dependence have a lower overall survival rate

Stimulation of the main pathogenic pathway for patients with myelofibrosis may paradoxically contribute to overcoming the issue of anemia for these individuals, according to new research findings presented at EHA 2018. T he research team from Spain found that patients who developed transfu- sion dependence during the course

This reality represents “a clinical challenge without effective therapeutic options,” the research team, led byMaría Isabel Montero, MD, with the Department of Hematology, Hospital Universitario Virgen del Rocio in Seville, Spain, noted in their abstract. “The underlying mechanisms of anemia in this patient population are not well established, although it has been associated with inef- fective hematopoiesis, elevated levels of proinflammatory cytokines, splenomegaly, mutations in several genes such as UAF1 or downregulation of certain proteins such as in the case of GATA1.” The investigators conducted a single- center analysis of the impact of anemia on survival and the response to erythropoietin treatment with JAK2 mutational status in a cohort of 119 patients diagnosed with myelofibrosis between June 1998 and July 2007. The average age at diagnosis was 67 years (range 19–88); 61% of patients were male and 36% had a previous diagnosis of another myeloproliferative neoplasm, specifically polycythemia vera or essential thrombocythemia. A diagnosis of myelofibrosis was made based on bone marrow examination and according to criteria established by the World Health Organization. V617F JAK2 status was assessed through

allele-specific polymerase chain reaction in patients diagnosed after 2005. Every patient who had clinically significant anemia received treatment with erythropoietin, a hormone produced by the kidney that promotes the production of red blood cells by bone marrow. The average leucocyte, hemoglobin, and platelet counts were 12,5 x 10e9/L, 114 g/L and 344 x 10e9/L, respectively. V617F JAK2 mutation was present in 61% of the patients. Of the total study group, 31% had a hemoglobin concentration less than 100 g/L at diagnosis, and 47% went on to develop a transfusion dependence. Overall, the 4-year OS rate was 69%. In patients with a hemoglobin concentration less than 100 g/L, OS was 56%. In those patients with a hemoglobin concentra- tion of at least 100 g/L, this figure rose to 77%. The difference is not statistically significant, the researchers stated in their abstract Is Anemia the Main Survival Marker in Patients With Myelofibrosis in the Ruxolitinib Era? For patients who developed transfusion dependence, the 4-year OS rate was 60%. This compared with 78% in those patients who did not have a transfusion dependence (P = .03). Only 20% of the patients with a V617F JAK2 mutation died compared with 56% of the patients with wild-type mutational status, the research- ers found. “However,” they noted in their abstract, “4-year OS rates among patients developing transfusion dependence were similar irrespective of their mutational sta- tus (65% if V617F JAK2-positive vs 60% if wild-type).”

of their disease had a lower overall survival (OS) rate, a finding that is consistent with published data. In addition, the investiga- tors concluded that patients with anemia and V617F JAK2 mutations responded better to erythropoietin treatment than those with JAK2 wild-type status, which raises the potential for using stimulation of the main pathogenic pathway. Myelofibrosis is an uncommon and seri- ous form of chronic leukemia that affects the body's normal production of blood cells. The disease causes significant scarring in the bone marrow, which often results in severe anemia as well as gen- eral weakness, fatigue, and an enlarged spleen. At diagnosis, roughly 50% of patients with myelofibrosis will have a hemoglobin concentration less than 100 g/L. Approximately 33% of patients will go on to develop transfusion depend- ence over the duration of their disease. Transfusion dependence indicates a condition of severe anemia typically aris- ing when erythropoiesis is reduced so significantly that blood transfusions are required over a specified interval. Being transfusion dependent is strongly corre- lated with decreased survival.

" The underlying mechanisms of anemia in this patient population are not well established, although it has been associated with ineffective hematopoiesis, elevated levels of proinflammatory cytokines, splenomegaly, mutations in several genes… " PRACTICEUPDATE CONFERENCE SERIES • EHA 2018 8

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