Characteristics and prognostic impact of <i>IDH</i> mutations in AML: a COG, SWOG, and ECOG analysis-Reference-Cited by-同舟云学术

Characteristics and prognostic impact of IDH mutations in AML: a COG, SWOG, and ECOG analysis

Published:2023-10-02 Issue:19 Volume:7 Page:5941-5953
ISSN:2473-9529
Container-title:Blood Advances
language:en
Short-container-title:

Author:

Zarnegar-Lumley Sara¹^ORCID,Alonzo Todd A.²³,Gerbing Robert B.²,Othus Megan⁴,Sun Zhuoxin⁵,Ries Rhonda E.⁶,Wang Jim²,Leonti Amanda⁶,Kutny Matthew A.⁷,Ostronoff Fabiana⁸,Radich Jerald P.⁶⁹,Appelbaum Frederick R.⁶⁹,Pogosova-Agadjanyan Era L.⁶^ORCID,O’Dwyer Kristen¹⁰,Tallman Martin S.¹¹,Litzow Mark¹²^ORCID,Atallah Ehab¹³,Cooper Todd M.¹⁴,Aplenc Richard A.¹⁵,Abdel-Wahab Omar¹¹¹⁶,Gamis Alan S.¹⁷^ORCID,Luger Selina¹⁸,Erba Harry¹⁹^ORCID,Levine Ross¹¹¹⁶,Kolb E. Anders²⁰,Stirewalt Derek L.⁶⁹,Meshinchi Soheil⁶,Tarlock Katherine⁶¹⁴

Affiliation:

1. 1Division of Hematology/Oncology, Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN

2. 2Children’s Oncology Group, Monrovia, CA

3. 3University of Southern California Keck School of Medicine, Los Angeles, CA

4. 4Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA

5. 5Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA

6. 6Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA

7. 7Division of Hematology/Oncology, Department of Pediatrics, The University of Alabama at Birmingham, Birmingham, AL

8. 8Intermountain Blood and Marrow Transplant and Acute Leukemia Program, Intermountain Healthcare, Salt Lake City, UT

9. 9Departments of Oncology and Hematology, University of Washington, Seattle, WA

10. 10Department of Medicine, Wilmot Cancer Institute, University of Rochester, Rochester, NY

11. 11Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, New York, NY

12. 12Department of Internal Medicine and Division of Hematology, Mayo Clinic College of Medicine, Rochester, MN

13. 13Division of Hematology/Oncology, Medical College of Wisconsin, Milwaukee, WI

14. 14Division of Hematology/Oncology, Seattle Children’s Hospital Cancer and Blood Disorders Center, University of Washington, Seattle, WA

15. 15Division of Oncology and Center for Childhood Cancer Research, Children’s Hospital of Philadelphia, Philadelphia, PA

16. 16Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY

17. 17Division of Hematology/Oncology/Bone Marrow Transplantation, Children’s Mercy Hospitals and Clinics, Kansas City, MO

18. 18Division of Hematology/Oncology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA

19. 19Division of Hematologic Malignancies and Cellular Therapies, Department of Medicine, Duke Cancer Institute, Durham, NC

20. 20Nemours Center for Cancer and Blood Disorders, Alfred I. DuPont Hospital for Children, Wilmington, DE

Abstract

Abstract Somatic mutations in isocitrate dehydrogenase (IDH) genes occur frequently in adult acute myeloid leukemia (AML) and less commonly in pediatric AML. The objective of this study was to describe the prevalence, mutational profile, and prognostic significance of IDH mutations in AML across age. Our cohort included 3141 patients aged between <1 month and 88 years treated on Children’s Cancer Group/Children’s Oncology Group (n = 1872), Southwest Oncology Group (n = 359), Eastern Cooperative Oncology Group (n = 397) trials, and in Beat AML (n = 333) and The Cancer Genome Atlas (n = 180) genomic characterization cohorts. We retrospectively analyzed patients in 4 age groups (age range, n): pediatric (0-17, 1744), adolescent/young adult (18-39, 444), intermediate-age (40-59, 640), older (≥60, 309). IDH mutations (IDHmut) were identified in 9.2% of the total cohort (n = 288; IDH1 [n = 123, 42.7%]; IDH2 [n = 165, 57.3%]) and were strongly correlated with increased age: 3.4% pediatric vs 21% older, P < .001. Outcomes were similar in IDHmut and IDH-wildtype (IDHWT) AML (event-free survival [EFS]: 35.6% vs 40.0%, P = .368; overall survival [OS]: 50.3% vs 55.4%, P = .196). IDH mutations frequently occurred with NPM1 (47.2%), DNMT3A (29.3%), and FLT3-internal tandem duplication (ITD) (22.4%) mutations. Patients with IDHmut AML with NPM1 mutation (IDHmut/NPM1mut) had significantly improved survival compared with the poor outcomes experienced by patients without (IDHmut/NPM1WT) (EFS: 55.1% vs 17.0%, P < .001; OS: 66.5% vs 35.2%, P < .001). DNTM3A or FLT3-ITD mutations in otherwise favorable IDHmut/NPM1mut AML led to inferior outcomes. Age group analysis demonstrated that IDH mutations did not abrogate the favorable prognostic impact of NPM1mut in patients aged <60 years; older patients had poor outcomes regardless of NPM1 status. These trials were registered at www.clinicaltrials.gov as #NCT00070174, #NCT00372593, #NCT01371981, #NCT00049517, and #NCT00085709.

Publisher

American Society of Hematology

Subject

Hematology

Link

https://ashpublications.org/bloodadvances/article-pdf/7/19/5941/2083746/blooda_adv-2022-008282-main.pdf

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