Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia.
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| Abstract | BACKGROUND: A single-group, phase 1-2 study indicated that eltrombopag improved the efficacy of standard immunosuppressive therapy that entailed horse antithymocyte globulin (ATG) plus cyclosporine in patients with severe aplastic anemia. METHODS: In this prospective, investigator-led, open-label, multicenter, randomized, phase 3 trial, we compared the efficacy and safety of horse ATG plus cyclosporine with or without eltrombopag as front-line therapy in previously untreated patients with severe aplastic anemia. The primary end point was a hematologic complete response at 3 months. RESULTS: Patients were assigned to receive immunosuppressive therapy (Group A, 101 patients) or immunosuppressive therapy plus eltrombopag (Group B, 96 patients). The percentage of patients who had a complete response at 3 months was 10% in Group A and 22% in Group B (odds ratio, 3.2; 95% confidence interval [CI], 1.3 to 7.8; P = 0.01). At 6 months, the overall response rate (the percentage of patients who had a complete or partial response) was 41% in Group A and 68% in Group B. The median times to the first response were 8.8 months (Group A) and 3.0 months (Group B). The incidence of severe adverse events was similar in the two groups. With a median follow-up of 24 months, a karyotypic abnormality that was classified as myelodysplastic syndrome developed in 1 patient (Group A) and 2 patients (Group B); event-free survival was 34% and 46%, respectively. Somatic mutations were detected in 29% (Group A) and 31% (Group Β) of the patients at baseline; these percentages increased to 66% and 55%, respectively, at 6 months, without affecting the hematologic response and 2-year outcome. CONCLUSIONS: The addition of eltrombopag to standard immunosuppressive therapy improved the rate, rapidity, and strength of hematologic response among previously untreated patients with severe aplastic anemia, without additional toxic effects. (Funded by Novartis and others; RACE ClinicalTrials.gov number, NCT02099747; EudraCT number, 2014-000363-40.).
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| Authors | Régis Peffault de Latour, Austin Kulasekararaj, Simona Iacobelli, Sofie R Terwel, Riley Cook, Morag Griffin, Constantijn J M Halkes, Christian Recher, Fiorenza Barraco, Edouard Forcade, Juan-Carlos Vallejo, Beatrice Drexler, Jean-Baptiste Mear, Alexander E Smith, Emanuele Angelucci, Reinier A P Raymakers, Marco R de Groot, Etienne Daguindau, Erfan Nur, Wilma Barcellini, Nigel H Russell, Louis Terriou, Anna-Paola Iori, Ursula La Rocca, Anna Sureda, Isabel Sánchez-Ortega, Blanca Xicoy, Isidro Jarque, James Cavenagh, Flore Sicre de Fontbrune, Serena Marotta, Talha Munir, Jennifer M L Tjon, Suzanne Tavitian, Aline Praire, Laurence Clement, Florence Rabian, Luana Marano, Anita Hill, Elena Palmisani, Petra Muus, Fabiana Cacace, Camilla Frieri, Maria-Teresa van Lint, Jakob R Passweg, Judith C W Marsh, Gérard Socié, Ghulam J Mufti, Carlo Dufour, Antonio M Risitano, Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation |
| Journal | The New England journal of medicine (N Engl J Med) Vol. 386 Issue 1 Pg. 11-23 (01 06 2022) ISSN: 1533-4406 [Electronic] United States |
| PMID | 34986284 (Publication Type: Clinical Trial, Phase III, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't) |
| Copyright | Copyright © 2022 Massachusetts Medical Society. |
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