Aplastic anemia is a difficult to treat disease. Younger patients, those under the age of 50, can proceed to an allogeneic stem cell transplant, but for older patients, the only effective strategy to prevent the complication of underproducing blood cells, is immunosupressive therapy. A recently approved drug for Idiopathic Throbocytopenic Purpura(ITP) can potentially raise platelet counts in aplastic anemia patients and was recently published in the New England Journal of Medicine.
This phase II trial included 25 patients with immunosuppression-refractory aplastic anemia who received eltrombopag at a dose of 50 mg, that was raised up to the maximum 150 mg daily in all but one patient, for a total of 12 weeks. Nine patients achieved a platelet rise of 20,000 cells/mm3 or more above baseline or independence from platelet transfusions for at least 8 weeks if previously transfusion-dependent. Two patients had a red cell response, with an increase in hemoglobin by 1.5 g/dL or more over pretreatment levels below 9 g/dL without transfusion of packed red cells or a reduction by at least 4 units transfused for 8 consecutive weeks. Four patients had a neutrophil response. Eight maintained a response without relapse for a median of 10 months. and six had a response in all three lineages.
These are promising results but the exchange of letters that followed the publication of this study drew attention to the potential risk of inducing progression to myelodysplastic syndromes or acute myeloid leukemia that needs to be conisdered in patients with aplastic anemia. There are reports of progression to acute myeloid leukemia in patients with myelodysplastic syndromes who are treated with romiplostim, another thrombopoietic, but the relative risk has not been defined. Nevertheless, the researchers who published this study did caution that treatment should be limited to clinical trials at this time. Therefore, I do not find sufficient justification to use Promacta before trying other therapies that the FDA requires.
Matthew J. Olnes, M.D., Ph.D., Phillip Scheinberg, M.D., Katherine R. Calvo, M.D., Ronan Desmond, M.D., Yong Tang, M.D., Ph.D., Bogdan Dumitriu, M.D., Ankur R. Parikh, M.D., Susan Soto, B.S.N., Angelique Biancotto, Ph.D., Xingmin Feng, M.D., Ph.D., Jay Lozier, M.D., Ph.D., Colin O. Wu, Ph.D., Neal S. Young, M.D., and Cynthia E. Dunbar, M.D.Eltrombopag and Improved Hematopoiesis in Refractory Aplastic Anemia. N Engl J Med 2012; 367:11-19July 5, 2012
Olnes MJ, Scheinberg P, Calvo KR, et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med 2012;367:11-19[Erratum, N Engl J Med 2012;367:284.
Olnes MJ, et al “Eltrombopag and improved hematopoiesis in refractory aplastic anemia” N Engl J Med 2012; 367: 11-19.
Metcalf D “A promising new treatment for refractory aplastic anemia” N Engl J Med 2012; 367: 74-75. See letters at: http://www.nejm.org/doi/full/10.1056/NEJMc1209254
Kantarjian H, Fenaux P, Sekeres MA, el al. Safety and efficacy of romiplostim in patients with lower-risk myelodysplastic syndrome and thrombocytopenia. J Clin Oncol 2010;28:437-444
Promacta, Pescribing Information 2015
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