Somatic gene mutation patterns and burden influence outcomes with enasidenib in relapsed/refractory IDH2-mutated AML
Copyright © 2024. Published by Elsevier Ltd..
Limited treatment options are available for patients with relapsed/refractory acute myeloid leukemia (R/R AML). We recently reported results from the phase 3 IDHENTIFY trial (NCT02577406) showing improved response rates and event-free survival with enasidenib monotherapy compared with conventional care regimens (CCR) in heavily pretreated, older patients with late-stage R/R AML bearing IDH2 mutations. Here we investigated the prognostic impact of mutational burden and different co-mutation patterns at study entry within the predominant IDH2 variant subclasses, IDH2-R140 and IDH2-R172. The prognostic relevance of these variants is well documented in newly diagnosed AML, but data are lacking in R/R AML. In this large R/R AML patient cohort, targeted next-generation sequencing at baseline (screening) revealed distinct co-mutation patterns and mutational burden between subgroups bearing different IDH2 variants: variant IDH2-R140 was associated with greater mutational burden and was enriched predominantly with poor-risk mutations, including FLT3, RUNX1, and NRAS, while variant IDH2-R172 was associated with lower mutational burden and was preferentially co-mutated with DNMT3A. In multivariable analyses, RAS and RTK pathway mutations were significantly associated with decreased overall survival, after adjusting for treatment arm, IDH2 variant, and mutational burden. Importantly, enasidenib-mediated survival benefit was more pronounced in patients with IDH2-R172 variants.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:140 |
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| Enthalten in: |
Leukemia research - 140(2024) vom: 27. März, Seite 107497 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Risueño, Alberto [VerfasserIn] |
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| Links: |
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| Themen: |
Acute myeloid leukemia |
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| Anmerkungen: |
Date Revised 02.04.2024 published: Print-Electronic Citation Status Publisher |
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| doi: |
10.1016/j.leukres.2024.107497 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM370544269 |
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| 520 | |a Limited treatment options are available for patients with relapsed/refractory acute myeloid leukemia (R/R AML). We recently reported results from the phase 3 IDHENTIFY trial (NCT02577406) showing improved response rates and event-free survival with enasidenib monotherapy compared with conventional care regimens (CCR) in heavily pretreated, older patients with late-stage R/R AML bearing IDH2 mutations. Here we investigated the prognostic impact of mutational burden and different co-mutation patterns at study entry within the predominant IDH2 variant subclasses, IDH2-R140 and IDH2-R172. The prognostic relevance of these variants is well documented in newly diagnosed AML, but data are lacking in R/R AML. In this large R/R AML patient cohort, targeted next-generation sequencing at baseline (screening) revealed distinct co-mutation patterns and mutational burden between subgroups bearing different IDH2 variants: variant IDH2-R140 was associated with greater mutational burden and was enriched predominantly with poor-risk mutations, including FLT3, RUNX1, and NRAS, while variant IDH2-R172 was associated with lower mutational burden and was preferentially co-mutated with DNMT3A. In multivariable analyses, RAS and RTK pathway mutations were significantly associated with decreased overall survival, after adjusting for treatment arm, IDH2 variant, and mutational burden. Importantly, enasidenib-mediated survival benefit was more pronounced in patients with IDH2-R172 variants | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Acute myeloid leukemia | |
| 650 | 4 | |a Enasidenib | |
| 650 | 4 | |a Gene mutation | |
| 650 | 4 | |a IDH2-mutated | |
| 650 | 4 | |a IDHENTIFY | |
| 650 | 4 | |a Relapsed/refractory | |
| 700 | 1 | |a See, Wendy L |e verfasserin |4 aut | |
| 700 | 1 | |a Bluemmert, Iryna |e verfasserin |4 aut | |
| 700 | 1 | |a de Botton, Stéphane |e verfasserin |4 aut | |
| 700 | 1 | |a DiNardo, Courtney D |e verfasserin |4 aut | |
| 700 | 1 | |a Fathi, Amir T |e verfasserin |4 aut | |
| 700 | 1 | |a Schuh, Andre C |e verfasserin |4 aut | |
| 700 | 1 | |a Montesinos, Pau |e verfasserin |4 aut | |
| 700 | 1 | |a Vyas, Paresh |e verfasserin |4 aut | |
| 700 | 1 | |a Prebet, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Gandhi, Anita |e verfasserin |4 aut | |
| 700 | 1 | |a Hasan, Maroof |e verfasserin |4 aut | |
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