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Eltrombopag does not improve outcomes in aplastic anemia

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January 8, 2019

The addition of eltrombopag to standard immunosuppressive therapy did not have a significant impact on response rates or survival outcomes among patients with newly diagnosed severe aplastic anemia, according to results of an open-label phase 2 trial.

Response rates to conventional immunosuppressive therapy among patients with severe aplastic anemia have been stagnant for 30 years at approximately 60%, according to Rita Assi, MD, fellow in the department of leukemia at The University of Texas MD Anderson Cancer Center, and colleagues.

Eltrombopag (Promacta, Novartis) is an oral thrombopoietin receptor agonist initially approved by the FDA for the treatment of chronic immune thrombocytopenic purpura.

In April, results of a prospective study demonstrated single-agent activity of eltrombopag in nearly 45% of patients with aplastic anemia refractory to standard immunosuppressive therapy. The FDA later approved eltrombopag in this patient setting.

For the current study, researchers enrolled 38 patients with newly diagnosed severe aplastic anemia to receive standard immunosuppressive therapy that consisted of horse antithymocyte globulin (Atgam, Pfizer) with cyclosporine A plus granulocyte colony-stimulating factors. The investigators later amended the trial after the FDA approval of eltrombopag to include the agent in 21 patients.

Overall response rate, including complete response and partial response, served as the primary endpoint. The tolerability and toxicities of the combination, time to response, duration of response and OS served as secondary endpoints.

Median follow-up was 21 months (range, 3-49).

Researchers reported no significant difference between the eltrombopag and standard therapy groups with regard to ORR (76% vs. 71%), complete remission rate (38% vs. 29%) or median time to response (84 days vs. 57 days).

Two-year OS was 91% in the standard therapy group and 82% in the eltrombopag group; again, the difference did not reach statistical significance.

“Although patients in both groups were treated sequentially and not in a comparative randomized fashion, we nevertheless expected better responses with the addition of eltrombopag to the combination of standard immunosuppressive therapy and granulocyte colony-stimulating factors, but instead observed similar outcomes,” Assi and colleagues wrote. “Maximizing dose intensity and the earlier initiation of eltrombopag may be important factors associated with higher responses. Longer follow-up is needed to determine the effect of eltrombopag, if any, on toOS in patients with aplastic anemia.”

In an accompanying editorial, H. Joachim Deeg, MD, professor in the division of medical oncology at the University of Washington School of Medicine, questioned whether the data warrant inclusion of eltrombopag in first-line therapy for all patients with aplastic anemia.

“It will be important to determine additional risk factors that identify patient populations that are unlikely to respond to standard immunosuppressive therapy and, therefore, should be given the potential benefit of added eltrombopag,” Deeg wrote. “Also, there are some preliminary data that raise the concern, without providing proof, that there may be a higher risk of developing clonal abnormalities with potential clinical significance in eltrombopag-treated patients. This possibility will need to be addressed as further studies are being conducted, and one will also have to consider the severity of aplastic anemia when designing new protocols and analyzing data.”– by Jennifer Southall

Disclosures: Assi reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures. Deeg report no relevant financial disclosures.

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