Eltrombopag in aplastic anemia

Abstract

The treatment of aplastic anemia is currently with immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG) and cyclosporine, to which two thirds of patients respond. However, a significant proportion of these responders relapse and many have persistent cytopenias. The management of these patients is challenging. Modifications to this standard approach using alternative immunosuppressive agents or adding hematopoietic cytokines such as granulocyte colony-stimulating factor (G-CSF) and erythropoietin (EPO) have not improved outcome. A recent trial has shown that eltrombopag, a thrombopoeitin mimetic, is efficacious in the treatment of patients with severe aplastic anemia (SAA) refractory to IST. There is evidence that this drug works by directly stimulating marrow stem and progenitor cells thereby promoting hematopoietic recovery in patients with bone marrow failure. Several trials are ongoing in our institution using this very promising drug in combination therapy in the upfront treatment of SAA, in IST-refractory SAA and in moderate disease.

Figure 1

Responses to eltrombopag by lineage in patients with SAA refractory to IST. These Venn diagrams show the numbers of patients with uni- and multilineage responses at response assessment (A) and best response at follow-up (B). Reprinted with permission.

Figure 2

Bone marrow cellularity in two patients responding to eltrombopag. The left panels show cellularity in these robust responders at baseline. The middle panels show cellularity just prior to discontinuing eltrombopag. The right panels demonstrate that, for Patients 1 and 2, the marrows remain cellular. The images were taken on an Olympus BX41 microscope with an Olympus DP72 camera, using a 4× UPlanFL N Olympus objective (original magnification ×40). Reprinted with permission.