TY - JOUR
T1 - Outcome of lower-risk patients with myelodysplastic syndromes without 5q deletion after failure of erythropoiesis-stimulating agents
AU - Park, Sophie
AU - Hamel, Jean François
AU - Toma, Andrea
AU - Kelaidi, Charikleia
AU - Thépot, Sylvain
AU - Campelo, Maria Diez
AU - Santini, Valeria
AU - Sekeres, Mikkael A.
AU - Balleari, Enrico
AU - Kaivers, Jennifer
AU - Sapena, Rosa
AU - Götze, Katharina
AU - Müller-Thomas, Catharina
AU - Beyne-Rauzy, Odile
AU - Stamatoullas, Aspasia
AU - Kotsianidis, Ioannis
AU - Komrokji, Rami
AU - Steensma, David P.
AU - Fensterl, Jaime
AU - Roboz, Gail J.
AU - Bernal, Teresa
AU - Ramos, Fernando
AU - Calabuig, Marisa
AU - Guerci-Bresler, Agnès
AU - Bordessoule, Dominique
AU - Cony-Makhoul, Pascale
AU - Cheze, Stéphane
AU - Wattel, Eric
AU - Rose, Christian
AU - Vey, Norbert
AU - Gioia, Daniela
AU - Ferrero, Dario
AU - Gaidano, Gianluca
AU - Cametti, Giovanni
AU - Pane, Fabrizio
AU - Sanna, Alessandro
AU - Germing, Ulrich
AU - Sanz, Guillermo F.
AU - Dreyfus, François
AU - Fenaux, Pierre
N1 - Publisher Copyright:
© 2017 by American Society of Clinical Oncology.
PY - 2017/5/10
Y1 - 2017/5/10
N2 - Purpose: Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Secondline treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods: We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results: Erythroid response to ESAs was 61.5%, and median response duration was 17 months. Of 1,147 patients experiencing ESA failure, 653 experienced primary failure and 494 experienced relapse after a response. Primary failure of ESAs was associated with a higher risk of acute myeloid leukemia (AML) progression, which did not translate into an OS difference. Of 450 patients (39%) who received second-line treatment, 194 received HMAs, 148 received LEN, and 108 received other treatments (MISC), whereas 697 received RBC transfusions only. Five-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for those receiving HMAs, LEN, and MISC, respectively (P =.05). Five-year OS for patients receiving HMA, LEN, and MISC was 36.5%, 41.7%, and 51%, respectively (P =.21). In a multivariable analysis adjusted for age, sex, revised International Prognostic Scoring System score, and progression at ESA failure, there was no significant OS difference among the three groups. Conclusion: In this large, multicenter, retrospective cohort of patients with non-del(5q) lower-risk MDS treated with ESAs, none of the most commonly used second-line treatments (HMA and LEN) significantly improved OS. Early failure of ESAs was associated with a higher risk of AML progression.
AB - Purpose: Most anemic patients with non-deleted 5q lower-risk myelodysplastic syndromes (MDS) are treated with erythropoiesis-stimulating agents (ESAs), with a response rate of approximately 50%. Secondline treatments, including hypomethylating agents (HMAs), lenalidomide (LEN), and investigational drugs, may be used after ESA failure in some countries, but their effect on disease progression and overall survival (OS) is unknown. Here, we analyzed outcome after ESA failure and the effect of second-line treatments. Patients and Methods: We examined an international retrospective cohort of 1,698 patients with non-del(5q) lower-risk MDS treated with ESAs. Results: Erythroid response to ESAs was 61.5%, and median response duration was 17 months. Of 1,147 patients experiencing ESA failure, 653 experienced primary failure and 494 experienced relapse after a response. Primary failure of ESAs was associated with a higher risk of acute myeloid leukemia (AML) progression, which did not translate into an OS difference. Of 450 patients (39%) who received second-line treatment, 194 received HMAs, 148 received LEN, and 108 received other treatments (MISC), whereas 697 received RBC transfusions only. Five-year AML cumulative incidence was 20.3%, 20.3%, and 11.3% for those receiving HMAs, LEN, and MISC, respectively (P =.05). Five-year OS for patients receiving HMA, LEN, and MISC was 36.5%, 41.7%, and 51%, respectively (P =.21). In a multivariable analysis adjusted for age, sex, revised International Prognostic Scoring System score, and progression at ESA failure, there was no significant OS difference among the three groups. Conclusion: In this large, multicenter, retrospective cohort of patients with non-del(5q) lower-risk MDS treated with ESAs, none of the most commonly used second-line treatments (HMA and LEN) significantly improved OS. Early failure of ESAs was associated with a higher risk of AML progression.
UR - http://www.scopus.com/inward/record.url?scp=85026885535&partnerID=8YFLogxK
U2 - 10.1200/JCO.2016.71.3271
DO - 10.1200/JCO.2016.71.3271
M3 - Article
C2 - 28350519
AN - SCOPUS:85026885535
SN - 0732-183X
VL - 35
SP - 1591
EP - 1597
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 14
ER -
