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Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial

This open-label, randomized, phase 3 trial (NCT02577406) compared enasidenib, an oral IDH2 (isocitrate dehydrogenase 2) inhibitor, with conventional care regimens (CCRs) in patients aged ≥60 years with late-stage, mutant-IDH2 acute myeloid leukemia (AML) relapsed/refractory (R/R) to 2 or 3 prior AML...

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Autores principales: de Botton, Stéphane, Montesinos, Pau, Schuh, Andre C., Papayannidis, Cristina, Vyas, Paresh, Wei, Andrew H., Ommen, Hans, Semochkin, Sergey, Kim, Hee-Je, Larson, Richard A., Koprivnikar, Jaime, Frankfurt, Olga, Thol, Felicitas, Chromik, Jörg, Byrne, Jenny, Pigneux, Arnaud, Thomas, Xavier, Salamero, Olga, Vidriales, Maria Belen, Doronin, Vadim, Döhner, Hartmut, Fathi, Amir T., Laille, Eric, Yu, Xin, Hasan, Maroof, Martin-Regueira, Patricia, DiNardo, Courtney D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society of Hematology 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644040/
https://www.ncbi.nlm.nih.gov/pubmed/35714312
http://dx.doi.org/10.1182/blood.2021014901
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author de Botton, Stéphane
Montesinos, Pau
Schuh, Andre C.
Papayannidis, Cristina
Vyas, Paresh
Wei, Andrew H.
Ommen, Hans
Semochkin, Sergey
Kim, Hee-Je
Larson, Richard A.
Koprivnikar, Jaime
Frankfurt, Olga
Thol, Felicitas
Chromik, Jörg
Byrne, Jenny
Pigneux, Arnaud
Thomas, Xavier
Salamero, Olga
Vidriales, Maria Belen
Doronin, Vadim
Döhner, Hartmut
Fathi, Amir T.
Laille, Eric
Yu, Xin
Hasan, Maroof
Martin-Regueira, Patricia
DiNardo, Courtney D.
author_facet de Botton, Stéphane
Montesinos, Pau
Schuh, Andre C.
Papayannidis, Cristina
Vyas, Paresh
Wei, Andrew H.
Ommen, Hans
Semochkin, Sergey
Kim, Hee-Je
Larson, Richard A.
Koprivnikar, Jaime
Frankfurt, Olga
Thol, Felicitas
Chromik, Jörg
Byrne, Jenny
Pigneux, Arnaud
Thomas, Xavier
Salamero, Olga
Vidriales, Maria Belen
Doronin, Vadim
Döhner, Hartmut
Fathi, Amir T.
Laille, Eric
Yu, Xin
Hasan, Maroof
Martin-Regueira, Patricia
DiNardo, Courtney D.
author_sort de Botton, Stéphane
collection PubMed
description This open-label, randomized, phase 3 trial (NCT02577406) compared enasidenib, an oral IDH2 (isocitrate dehydrogenase 2) inhibitor, with conventional care regimens (CCRs) in patients aged ≥60 years with late-stage, mutant-IDH2 acute myeloid leukemia (AML) relapsed/refractory (R/R) to 2 or 3 prior AML-directed therapies. Patients were first preselected to a CCR (azacitidine, intermediate-dose cytarabine, low-dose cytarabine, or supportive care) and then randomized (1:1) to enasidenib 100 mg per day or CCR. The primary endpoint was overall survival (OS). Secondary endpoints included event-free survival (EFS), time to treatment failure (TTF), overall response rate (ORR), hematologic improvement (HI), and transfusion independence (TI). Overall, 319 patients were randomized to enasidenib (n = 158) or CCR (n = 161). The median age was 71 years, median (range) enasidenib exposure was 142 days (3 to 1270), and CCR was 36 days (1 to 1166). One enasidenib (0.6%) and 20 CCR (12%) patients received no randomized treatment, and 30% and 43%, respectively, received subsequent AML-directed therapies during follow-up. The median OS with enasidenib vs CCR was 6.5 vs 6.2 months (HR [hazard ratio], 0.86; P = .23); 1-year survival was 37.5% vs 26.1%. Enasidenib meaningfully improved EFS (median, 4.9 vs 2.6 months with CCR; HR, 0.68; P = .008), TTF (median, 4.9 vs 1.9 months; HR, 0.53; P < .001), ORR (40.5% vs 9.9%; P <.001), HI (42.4% vs 11.2%), and red blood cell (RBC)-TI (31.7% vs 9.3%). Enasidenib safety was consistent with prior reports. The primary study endpoint was not met, but OS was confounded by early dropout and subsequent AML-directed therapies. Enasidenib provided meaningful benefits in EFS, TTF, ORR, HI, and RBC-TI in this heavily pretreated older mutant-IDH2 R/R AML population.
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spelling pubmed-106440402023-11-14 Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial de Botton, Stéphane Montesinos, Pau Schuh, Andre C. Papayannidis, Cristina Vyas, Paresh Wei, Andrew H. Ommen, Hans Semochkin, Sergey Kim, Hee-Je Larson, Richard A. Koprivnikar, Jaime Frankfurt, Olga Thol, Felicitas Chromik, Jörg Byrne, Jenny Pigneux, Arnaud Thomas, Xavier Salamero, Olga Vidriales, Maria Belen Doronin, Vadim Döhner, Hartmut Fathi, Amir T. Laille, Eric Yu, Xin Hasan, Maroof Martin-Regueira, Patricia DiNardo, Courtney D. Blood Clinical Trials and Observations This open-label, randomized, phase 3 trial (NCT02577406) compared enasidenib, an oral IDH2 (isocitrate dehydrogenase 2) inhibitor, with conventional care regimens (CCRs) in patients aged ≥60 years with late-stage, mutant-IDH2 acute myeloid leukemia (AML) relapsed/refractory (R/R) to 2 or 3 prior AML-directed therapies. Patients were first preselected to a CCR (azacitidine, intermediate-dose cytarabine, low-dose cytarabine, or supportive care) and then randomized (1:1) to enasidenib 100 mg per day or CCR. The primary endpoint was overall survival (OS). Secondary endpoints included event-free survival (EFS), time to treatment failure (TTF), overall response rate (ORR), hematologic improvement (HI), and transfusion independence (TI). Overall, 319 patients were randomized to enasidenib (n = 158) or CCR (n = 161). The median age was 71 years, median (range) enasidenib exposure was 142 days (3 to 1270), and CCR was 36 days (1 to 1166). One enasidenib (0.6%) and 20 CCR (12%) patients received no randomized treatment, and 30% and 43%, respectively, received subsequent AML-directed therapies during follow-up. The median OS with enasidenib vs CCR was 6.5 vs 6.2 months (HR [hazard ratio], 0.86; P = .23); 1-year survival was 37.5% vs 26.1%. Enasidenib meaningfully improved EFS (median, 4.9 vs 2.6 months with CCR; HR, 0.68; P = .008), TTF (median, 4.9 vs 1.9 months; HR, 0.53; P < .001), ORR (40.5% vs 9.9%; P <.001), HI (42.4% vs 11.2%), and red blood cell (RBC)-TI (31.7% vs 9.3%). Enasidenib safety was consistent with prior reports. The primary study endpoint was not met, but OS was confounded by early dropout and subsequent AML-directed therapies. Enasidenib provided meaningful benefits in EFS, TTF, ORR, HI, and RBC-TI in this heavily pretreated older mutant-IDH2 R/R AML population. The American Society of Hematology 2023-01-12 2022-06-20 /pmc/articles/PMC10644040/ /pubmed/35714312 http://dx.doi.org/10.1182/blood.2021014901 Text en © 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Clinical Trials and Observations
de Botton, Stéphane
Montesinos, Pau
Schuh, Andre C.
Papayannidis, Cristina
Vyas, Paresh
Wei, Andrew H.
Ommen, Hans
Semochkin, Sergey
Kim, Hee-Je
Larson, Richard A.
Koprivnikar, Jaime
Frankfurt, Olga
Thol, Felicitas
Chromik, Jörg
Byrne, Jenny
Pigneux, Arnaud
Thomas, Xavier
Salamero, Olga
Vidriales, Maria Belen
Doronin, Vadim
Döhner, Hartmut
Fathi, Amir T.
Laille, Eric
Yu, Xin
Hasan, Maroof
Martin-Regueira, Patricia
DiNardo, Courtney D.
Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial
title Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial
title_full Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial
title_fullStr Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial
title_full_unstemmed Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial
title_short Enasidenib vs conventional care in older patients with late-stage mutant-IDH2 relapsed/refractory AML: a randomized phase 3 trial
title_sort enasidenib vs conventional care in older patients with late-stage mutant-idh2 relapsed/refractory aml: a randomized phase 3 trial
topic Clinical Trials and Observations
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10644040/
https://www.ncbi.nlm.nih.gov/pubmed/35714312
http://dx.doi.org/10.1182/blood.2021014901
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