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Platelet drug improved blood count in aplastic anemia patients
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The platelet drug eltrombopag produced a hematologic response with minimal toxic effects in some patients with refractory aplastic anemia, according to results of a phase 2 study.
Severe aplastic anemia is a condition in which the bone marrow fails to produce enough blood cells. It can be treated with immunosuppression or allogeneic transplantation. One-third of patients with aplastic anemia are resistant to immunosuppression, causing severe cytopenia and a shortage in hematopoietic stem cells and progenitor cells, according to researchers.
Given orally, eltrombopag (Promacta, GlaxoSmithKline) is designed to improve the production of bone marrow blood cells.
Matthew J. Olnes, MD, PhD, staff clinician for the Center for Human Immunology and Inflammation at the NIH, and colleagues conducted the study to evaluate the efficacy of eltrombopag in escalating blood counts.
Researchers enrolled 25 patients dependent on platelet transfusions between 2009 and 2011. All 25 patients received 50 mg eltrombopag daily for 12 weeks. Doses could be increased as needed to a maximum of 150 mg daily. Patients with a response continued to receive the drug.
Eleven of the 25 patients (44%) had a hematologic response in at least one lineage at 12 weeks with minimal adverse toxic effects, according to study results. Response was maintained for a median of 10 months in eight of the 11 patients. Seven patients continued to receive the drug at 150 mg daily for a median of 16 months.
At 12 weeks, eltrombopag raised the platelet count of nine patients at a median of 44,000/mm3. Those nine patients discontinued their platelet transfusions.
Six patients improved their hemoglobin levels with a median increase of 4.4 g/dL. Neutrophil response was observed in nine patients, with a median increase of 1,350 cells/mm3.
Treatment with eltrombopag was associated with improved blood counts for patients with severe refractory aplastic anemia, but more data are needed to determine whether adding eltrombopag to up-front immunosuppressive therapy can improve the rate of responses in aplastic anemia, the researchers concluded.
“If confirmed, the implication of these intriguing results is that in many patients with aplastic anemia, the hematopoietic stem cells and their progenitor-cell progeny may have acquired defective MPL receptors that are unresponsive to thrombopoietin but remain able to be activated by eltrombopag,” Donald Metcalf, MD, professor emeritus in the division of cancer and hematology at The Walter and Eliza Hall Institute of Medical Research in Australia, wrote in an accompanying editorial. “Of particular interest is a recent study in which patients with familial aplastic anemia were shown to have nonsense mutations in the MPL gene. Time will tell whether the hematopoietic cells in other patients with aplastic anemia will also prove to have defective MPL signaling.”
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