TY - JOUR
T1 - Eltrombopag Added to Immunosuppression in Severe Aplastic Anemia
AU - de Latour, R. gis Peffault
AU - Kulasekararaj, Austin
AU - Iacobelli, Si-Mona
AU - Terwel, Sofie R.
AU - Cook, Riley
AU - Griffin, Morag
AU - Halkes, Constantijn J. M.
AU - Recher, Christian
AU - Barraco, Fiorenza
AU - Forcade, Edouard
AU - Vallejo, Juan-Carlos
AU - Drexler, Beatrice
AU - Mear, Jean-Baptiste
AU - Smith, Alexander E.
AU - Angelucci, Emanuele
AU - Raymakers, Reinier A. P.
AU - de Groot, Marco R.
AU - Daguindau, Etienne
AU - Nur, Erfan
AU - Barcellini, Wilma
AU - Russell, Nigel H.
AU - Terriou, Louis
AU - Iori, Anna-Paola
AU - la Rocca, Ursula
AU - Sureda, Anna
AU - Sánchez-Ortega, Isabel
AU - Xicoy, Blanca
AU - Jarque, Isidro
AU - Cavenagh, James
AU - de Fontbrune, Flore Sicre
AU - Marotta, Serena
AU - Munir, Talha
AU - Tjon, Jennifer M. L.
AU - Tavitian, Suzanne
AU - Praire, Aline
AU - Clement, Laurence
AU - Rabian, Florence
AU - Marano, Luana
AU - Hill, Anita
AU - Palmisani, Elena
AU - Muus, Petra
AU - Cacace, Fabiana
AU - Frieri, Camilla
AU - van Lint, Maria-Teresa
AU - Passweg, Jakob R.
AU - Marsh, Judith C. W.
AU - Socié, G. rard
AU - Mufti, Ghulam J.
AU - Dufour, Carlo
AU - Risitano, Antonio M.
N1 - Funding Information: Supported by Novartis, Pfizer, a grant from Alexion Pharma, a grant (A22324) from Cancer Research UK, and grants (10024 and 14017) from Bloodwise UK (previously called Leukaemia and Lymphoma Research). Publisher Copyright: Copyright © 2022 Massachusetts Medical Society.
PY - 2022/1/6
Y1 - 2022/1/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85122724724&partnerID=8YFLogxK
U2 - https://doi.org/10.1056/NEJMoa2109965
DO - https://doi.org/10.1056/NEJMoa2109965
M3 - Article
C2 - 34986284
SN - 0028-4793
VL - 386
SP - 11
EP - 23
JO - New England journal of medicine
JF - New England journal of medicine
IS - 1
ER -