Clinical characteristics and outcomes of EZH2-mutant myelodysplastic syndrome: A large single institution analysis of 1774 patients

EZH2 mutations in myeloid neoplasms are loss of function type, and have been linked to poor overall survival (OS) in patients with myelodysplastic syndrome (MDS). However, the specific determinants of outcomes in EZH2-mutant (mut) MDS are not well characterized. In this single-center retrospective s...

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Published in:Leukemia research 2023-01, Vol.124, p.106999-106999, Article 106999
Main Authors: Ball, Somedeb, Aguirre, Luis E., Jain, Akriti G., Ali, Najla Al, Tinsley, Sara M., Chan, Onyee, Kuykendall, Andrew T., Sweet, Kendra, Lancet, Jeffrey E., Sallman, David A., Hussaini, Mohammad Omar, Padron, Eric, Komrokji, Rami S.
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Language:English
Subjects:
Aged
ASXL1
Chromosome Aberrations
Deletion 7q
Enhancer of Zeste Homolog 2 Protein - genetics
EZH2
Humans
Hypomethylating agent
Mutation
Myelodysplastic Syndromes - therapy
Myeloproliferative Disorders
Overall survival
Prognosis
Retrospective Studies
RUNX1
Transcription Factors - genetics
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container_title Leukemia research
container_volume 124
creator Ball, Somedeb
Aguirre, Luis E.
Jain, Akriti G.
Ali, Najla Al
Tinsley, Sara M.
Chan, Onyee
Kuykendall, Andrew T.
Sweet, Kendra
Lancet, Jeffrey E.
Sallman, David A.
Hussaini, Mohammad Omar
Padron, Eric
Komrokji, Rami S.
description EZH2 mutations in myeloid neoplasms are loss of function type, and have been linked to poor overall survival (OS) in patients with myelodysplastic syndrome (MDS). However, the specific determinants of outcomes in EZH2-mutant (mut) MDS are not well characterized. In this single-center retrospective study, clinical and genomic data were collected on 1774 patients with MDS treated at Moffitt Cancer Center. In our cohort, 83 (4.7%) patients had a pathogenic EZH2 mutation. Patients with EZH2mut MDS were older than EZH2-wild type (wt) group (median age- 72 vs. 69 years, p = 0.010). The most common co-occurring mutation in EZH2mut MDS was ASXL1, with a significantly higher frequency than EZH2wt (54% vs. 19%, p 
doi_str_mv 10.1016/j.leukres.2022.106999
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However, the specific determinants of outcomes in EZH2-mutant (mut) MDS are not well characterized. In this single-center retrospective study, clinical and genomic data were collected on 1774 patients with MDS treated at Moffitt Cancer Center. In our cohort, 83 (4.7%) patients had a pathogenic EZH2 mutation. Patients with EZH2mut MDS were older than EZH2-wild type (wt) group (median age- 72 vs. 69 years, p = 0.010). The most common co-occurring mutation in EZH2mut MDS was ASXL1, with a significantly higher frequency than EZH2wt (54% vs. 19%, p &lt; 0.001). Patients with EZH2mut MDS had lower response rates to hypomethylating agents compared to EZH2wt MDS (26% vs. 39%; p = 0.050). Median OS of patients with EZH2mut MDS was 30.8 months, with a significantly worse OS than EZH2wt group (35.5 vs. 61.2 months, p = 0.003) in the lower-risk IPSS-R categories. Among patients with EZH2mut MDS, co-presence of ASXL1 or RUNX1 mutations was associated with inferior median OS compared to their wt counterparts (26.8 vs. 48.7 months, p = 0.031). Concurrent chromosome 7 abnormalities (12%) were also associated with significantly worse OS (median OS- 20.8 vs. 35.5 months, p = 0.002) in EZH2mut MDS. Future clinical trials should explore the potential role of novel targeted therapies in improving outcomes in patients with EZH2mut MDS. •Incidence of EZH2 mutation in MDS is 4.7%.•EZH2-mutant MDS commonly harbored concurrent deleterious ASXL1 and RUNX1 mutations.•EZH2 mutation in MDS is associated with lower response rate to HMA.•Presence of chromosome 7 abnormalities confer inferior OS in EZH2-mutant MDS.•EZH2-mutant MDS had worse OS compared to wild type in patients with lower-risk MDS.</description><identifier>ISSN: 0145-2126</identifier><identifier>EISSN: 1873-5835</identifier><identifier>DOI: 10.1016/j.leukres.2022.106999</identifier><identifier>PMID: 36542963</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Aged ; ASXL1 ; Chromosome Aberrations ; Deletion 7q ; Enhancer of Zeste Homolog 2 Protein - genetics ; EZH2 ; Humans ; Hypomethylating agent ; Mutation ; Myelodysplastic Syndromes - therapy ; Myeloproliferative Disorders ; Overall survival ; Prognosis ; Retrospective Studies ; RUNX1 ; Transcription Factors - genetics</subject><ispartof>Leukemia research, 2023-01, Vol.124, p.106999-106999, Article 106999</ispartof><rights>2022 Elsevier Ltd</rights><rights>Copyright © 2022 Elsevier Ltd. 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Among patients with EZH2mut MDS, co-presence of ASXL1 or RUNX1 mutations was associated with inferior median OS compared to their wt counterparts (26.8 vs. 48.7 months, p = 0.031). Concurrent chromosome 7 abnormalities (12%) were also associated with significantly worse OS (median OS- 20.8 vs. 35.5 months, p = 0.002) in EZH2mut MDS. Future clinical trials should explore the potential role of novel targeted therapies in improving outcomes in patients with EZH2mut MDS. •Incidence of EZH2 mutation in MDS is 4.7%.•EZH2-mutant MDS commonly harbored concurrent deleterious ASXL1 and RUNX1 mutations.•EZH2 mutation in MDS is associated with lower response rate to HMA.•Presence of chromosome 7 abnormalities confer inferior OS in EZH2-mutant MDS.•EZH2-mutant MDS had worse OS compared to wild type in patients with lower-risk MDS.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>36542963</pmid><doi>10.1016/j.leukres.2022.106999</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-2872-1961</orcidid><orcidid>https://orcid.org/0000-0002-1754-1204</orcidid></addata></record>
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subjects Aged
ASXL1
Chromosome Aberrations
Deletion 7q
Enhancer of Zeste Homolog 2 Protein - genetics
EZH2
Humans
Hypomethylating agent
Mutation
Myelodysplastic Syndromes - therapy
Myeloproliferative Disorders
Overall survival
Prognosis
Retrospective Studies
RUNX1
Transcription Factors - genetics
title Clinical characteristics and outcomes of EZH2-mutant myelodysplastic syndrome: A large single institution analysis of 1774 patients
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