April 19, 2017
3 min read

Eltrombopag shows promise as first treatment for severe aplastic anemia

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The addition of eltrombopag to immunosuppressive therapy increased hematologic response rates among patients with aplastic anemia compared with historical rates, according to results of a prospective study.

Eltrombopag (Promacta, Novartis) — an oral thrombopoietin receptor agonist — has demonstrated activity as a single agent in refractory severe aplastic anemia, conferring hematologic responses in approximately 45% of patients.

Danielle M. Townsley
Neal S. Young

“Immunosuppressive therapies have been successful in blocking the immune system that destroys bone marrow stem cells in aplastic anemia,” Danielle M. Townsley, MD, staff clinician in the hematology branch of the National Heart, Lung and Blood Institute of the NIH, and Neal S. Young, MD, chief of the hematology branch of the National Heart, Lung, and Blood Institute and director of the Center for Human Immunology of the NIH, told HemOnc Today. “The current work demonstrates that stimulating remaining stem cells with a drug that mimics the actions of a natural growth substance for marrow stem cells while suppressing the immune system improves the likelihood, quality and speed of recovery of these seriously ill patients.”

The researchers enrolled 92 patients with newly diagnosed severe aplastic anemia from Hatfield Clinical Center in Bethesda, Maryland, to receive immunosuppressive therapy — consisting of horse antithymocyte globulin (Atgam, Pfizer) and cyclosporine — with eltrombopag (age 12 years and older, 150 mg daily; 6 to 11 years, 75 mg daily; 2 to 5 years, 2.5 mg/kg daily).

The patients were divided into three cohorts based on the initiation and duration of eltrombopag: day 14 until 6 months (cohort 1; n = 31); day 14 until 3 months (cohort 2; n = 33); and concurrently from day 1 through 6 months (cohort 3; n = 31).

Complete response at 6 months served as the primary efficacy endpoint. Safety profile in the 6 months after treatment initiation served as the primary safety endpoint. Secondary endpoints included, but were not limited to, partial and overall hematologic response at 3 months, 6 months, and each year during follow-up; survival; self-reported health outcomes; and relapse.

Researchers analyzed the results of each cohort separately for primary endpoints. Further, researchers compared results of secondary endpoints in each cohort and all cohorts combined with a historical cohort of 102 patients who received standard immunosuppressive therapy in one of two earlier clinical trials.

Median follow-up was 703 days (range, 84-1,422) among the entire cohort and 713 days (range, 194-1,422) for survivors.

Rates of complete response at 6 months were 33% in patients in cohort 1, 26% in cohort 2 and 58% in cohort 3. Overall response rates were 80% in cohort 1, 87% in cohort 2 and 94% in cohort 3.


The combined cohorts achieved higher complete and overall response rates than the historical cohort, which had a 10% complete response rate and 66% ORR.

“Strikingly, a much higher number of patients responded to eltrombopag combined with immunosuppressive therapy compared with prior results in these patients using immunosuppression alone,” Townsley and Young said. “Overall, 80% responded with improved blood counts and independence from transfusions, with almost all responding patients showing markedly better, near normal blood counts by 6 months after beginning treatment.”

The survival rate among all cohorts was 97% at a median follow-up of 2 years (95% CI, 94-100).

Patients who responded by 6 months had significantly higher levels of physical health and overall health-related quality of life than patients who did not respond.

Seven patients briefly discontinued eltrombopag during the first 2 weeks of therapy due to transient elevations in liver enzyme levels. Two patients discontinued treatment later due to grade 2 and grade 3 cutaneous eruptions related to eltrombopag. Adverse events that were observed and unrelated to eltrombopag included neutropenic infections and toxic effects from immunosuppressive therapy.

One patient died during the study of a nonhematologic cause. This death was not due to bone marrow or blood causes, and the “majority of patients tolerated the drug treatment very well,” Townsley and Young said.

A large placebo-controlled trial is underway in Europe to confirm results, the researchers wrote.

“Eltrombopag is under study in other [NHLBI Hematology Branch] protocols and at academic institutions to treat additional types of bone marrow failure, and may also benefit patients in developing countries where aplastic anemia is more common and bone marrow transplantation and other intensive therapies for marrow failure are unavailable,” Townsley and Young said. – by Melinda Stevens

For more information:

Danielle M. Townsley, MD, can be reached at National Heart, Lung, and Blood Institute, Bldg. 10-CRC, Rm. 3-5216, 10 Center Dr., Bethesda, MD 20892; email: townsleydm@nhlbi.nih.gov.

Neal S. Young, MD, can be reached at National Heart, Lung, and Blood Institute, Bldg. 10-CRC Room 3-5142, Bethesda, MD 20814; email: youngns@mail.nih.gov.

Disclosures: Townsley and Young report research funding from GlaxoSmithKline and Novartis during the conduct of the study. Please see the full study for a list of all other researchers’ relevant financial disclosures.