Durable remissions with ivosidenib in IDH1-mutated relapsed or refractory AML

New England Journal of Medicine

Volumn 378, Issue 25, 2018, Pages 2386-2398

  DiNardo, C D ^a   Stein, E M ^b   De Botton, S ^d   Roboz, G J ^c   Altman, J K ^f   Mims, A S ^g   Swords, R ^h   Collins, R H ⁱ   Mannis, G N ^j   Pollyea, D A ^l   Donnellan, W ^m   Fathi, A T ⁿ   Pigneux, A ^e   Erba, H P ^q   Prince, G T ^r   Stein, A S ^k   Uy, G L ^s   Foran, J M ^t   Traer, E ^u   Stuart, R K ^v   Arellano, M L ^w   Slack, J L ^x   Sekeres, M A ^y   Willekens, C ^d   Choe, S ^p   Wang, H ^p   Zhang, V ^p   Yen, K E ^p   Kapsalis, S M ^p   Yang, H ^p   Dai, D ^p   Fan, B ^p   Goldwasser, M ^p   Liu, H ^p   Agresta, S ^p   Wu, B ^p   Attar, E C ^p   Tallman, M S ^b   Stone, R M ^o   Kantarjian, H M ^a   more..

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

^c WEILL CORNELL MEDICAL COLLEGE   (United States)

^d INSTITUT GUSTAVE ROUSSY   (France)

^e BORDEAUX UNIVERSITY HOSPITAL   (France)

^f NORTHWESTERN UNIVERSITY   (United States)

^g THE OHIO STATE UNIVERSITY WEXNER MEDICAL CENTER   (United States)

^h UNIVERSITY OF MIAMI   (United States)

ⁱ UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^j UNIVERSITY OF CALIFORNIA   (United States)

^k CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^l UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^m SARAH CANNON RESEARCH INSTITUTE   (United States)

ⁿ MASSACHUSETTS GENERAL HOSPITAL CANCER CENTER   (United States)

^o DANA FARBER CANCER INSTITUTE   (United States)

^p AGIOS PHARMACEUTICALS   (United States)

^q UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^r JOHNS HOPKINS UNIVERSITY   (United States)

^s WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^t MAYO CLINIC   (United States)

^u OREGON HEALTH AND SCIENCE UNIVERSITY   (United States)

^v MEDICAL UNIVERSITY OF SOUTH CAROLINA   (United States)

^w EMORY UNIVERSITY   (United States)

^x MAYO CLINIC   (United States)

^y LERNER RESEARCH INSTITUTE   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ISOCITRATE DEHYDROGENASE 1; IVOSIDENIB; ENZYME INHIBITOR; HEMOGLOBIN; IDH1 PROTEIN, HUMAN; ISOCITRATE DEHYDROGENASE;

ACUTE MYELOID LEUKEMIA; ADULT; AGED; ANEMIA; ARTICLE; BLOOD TRANSFUSION; CONTROLLED STUDY; COUGHING; DIARRHEA; DRUG DOSE ESCALATION; DRUG DOSE INCREASE; DRUG EFFICACY; DRUG RESPONSE; DRUG SAFETY; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; FEVER; FOLLOW UP; GENE MUTATION; HEMATOLOGIC DISEASE; HUMAN; IDH DIFFERENTIATION SYNDROME; IDH1 GENE; INFECTION; LEUKEMIA RELAPSE; LEUKEMIA REMISSION; LEUKOCYTOSIS; MAJOR CLINICAL STUDY; MALE; MONOTHERAPY; PERIPHERAL EDEMA; PHASE 1 CLINICAL TRIAL; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; QT PROLONGATION; THROMBOCYTE DISORDER; THROMBOCYTOPENIA; TREATMENT OUTCOME; VERY ELDERLY; ADOLESCENT; ANTAGONISTS AND INHIBITORS; CELL COUNT; CLINICAL TRIAL; DOSE RESPONSE; DRUG RESISTANCE; GENETICS; MIDDLE AGED; MORTALITY; MULTICENTER STUDY; MUTATION; ORAL DRUG ADMINISTRATION; RECURRENT DISEASE; REMISSION; SURVIVAL RATE; YOUNG ADULT;

ADMINISTRATION, ORAL; ADOLESCENT; ADULT; AGED; AGED, 80 AND OVER; CELL COUNT; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG RESISTANCE, NEOPLASM; ENZYME INHIBITORS; FEMALE; FOLLOW-UP STUDIES; HEMOGLOBINS; HUMANS; ISOCITRATE DEHYDROGENASE; LEUKEMIA, MYELOID, ACUTE; MALE; MIDDLE AGED; MUTATION; RECURRENCE; REMISSION INDUCTION; SURVIVAL RATE; YOUNG ADULT;

EID: 85049221548     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMoa1716984     Document Type: Article

References (22)

1. Dang L, White DW, Gross S, et al. Cancer-associated IDH1 mutations produce 2-hydroxyglutarate. Nature 2009; 462: 739-44.
2. Ward PS, Patel J, Wise DR, et al. The common feature of leukemia-associated IDH1 and IDH2 mutations is a neomorphic enzyme activity converting alphaketoglutarate to 2-hydroxyglutarate. Cancer Cell 2010; 17: 225-34.
3. Figueroa ME, Abdel-Wahab O, Lu C, et al. Leukemic IDH1 and IDH2 mutations result in a hypermethylation phenotype, disrupt TET2 function, and impair hematopoietic differentiation. Cancer Cell 2010; 18: 553-67.
4. Lu C, Ward PS, Kapoor GS, et al. IDH mutation impairs histone demethylation and results in a block to cell differentiation. Nature 2012; 483: 474-8.
5. Xu W, Yang H, Liu Y, et al. Oncometabolite 2-hydroxyglutarate is a competitive inhibitor of a-ketoglutaratedependent dioxygenases. Cancer Cell 2011; 19: 17-30.
6. Mardis ER, Ding L, Dooling DJ, et al. Recurring mutations found by sequencing an acute myeloid leukemia genome. N Engl J Med 2009; 361: 1058-66.
7. Patel KP, Ravandi F, Ma D, et al. Acute myeloid leukemia with IDH1 or IDH2 mutation: frequency and clinicopathologic features. Am J Clin Pathol 2011; 135: 35-45.
8. DiNardo CD, Ravandi F, Agresta S, et al. Characteristics, clinical outcome, and prognostic significance of IDH mutations in AML. Am J Hematol 2015; 90: 732-6.
9. Paschka P, Schlenk RF, Gaidzik VI, et al. IDH1 and IDH2 mutations are frequent genetic alterations in acute myeloid leukemia and confer adverse prognosis in cytogenetically normal acute myeloid leukemia with NPM1 mutation without FLT3 internal tandem duplication. J Clin Oncol 2010; 28: 3636-43.
10. Popovici-Muller J, Lemieux RM, Artin E, et al. Discovery of AG-120 (ivosidenib): a first-in-class mutant IDH1 inhibitor for the treatment of IDH1 mutant cancers. ACS Med Chem Lett 2018; 9: 300-5.
11. Yen K, Travins J, Wang F, et al. AG-221, a first-in-class therapy targeting acute myeloid leukemia harboring oncogenic IDH2 mutations. Cancer Discov 2017; 7: 478-93.
12. Stein EM, DiNardo CD, Pollyea DA, et al. Enasidenib in mutant IDH2 relapsed or refractory acute myeloid leukemia. Blood 2017; 130: 722-31.
13. IDHIFA (enasidenib). Summit, NJ: Celgene, August 2017 (package insert) (https://www .accessdata .fda .gov/drugsatfda-docs/label/2017/209606s000lbl .pdf).
14. Hansen E, Quivoron C, Straley K, et al. AG-120, an oral, selective, first-inclass, potent inhibitor of mutant IDH1, reduces intracellular 2HG and induces cellular differentiation in TF-1 R132H cells and primary human IDH1 mutant AML patient samples treated ex vivo. Blood 2014; 124: A3734. abstract.
15. Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 2003; 21: 4642-9.
16. Dressman D, Yan H, Traverso G, Kinzler KW, Vogelstein B. Transforming single DNA molecules into fluorescent magnetic particles for detection and enumeration of genetic variations. Proc Natl Acad Sci U S A 2003; 100: 8817-22.
17. Birendra KC, DiNardo CD. Evidence for clinical differentiation and differentiation syndrome in patients with acute myeloid leukemia and IDH1 mutations treated with the targeted mutant IDH1 inhibitor, AG-120. Clin Lymphoma Myeloma Leuk 2016; 16: 460-5.
18. Feng JH, Guo XP, Chen YY, Wang ZJ, Cheng YP, Tang YM. Prognostic significance of IDH1 mutations in acute myeloid leukemia: a meta-analysis. Am J Blood Res 2012; 2: 254-64.
19. Xu Q, Li Y, Lv N, et al. Correlation between isocitrate dehydrogenase gene aberrations and prognosis of patients with acute myeloid leukemia: a systematic review and meta-analysis. Clin Cancer Res 2017; 23: 4511-22.
20. Zhou KG, Jiang LJ, Shang Z, Wang J, Huang L, Zhou JF. Potential application of IDH1 and IDH2 mutations as prognostic indicators in non-promyelocytic acute myeloid leukemia: a meta-analysis. Leuk Lymphoma 2012; 53: 2423-9.
21. Roboz GJ, Rosenblat T, Arellano M, et al. International randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia. J Clin Oncol 2014; 32: 1919-26.
22. Fathi AT, DiNardo CD, Kline I, et al. Differentiation syndrome associated with enasidenib, a selective inhibitor of mutant isocitrate dehydrogenase 2: analysis of a phase 1/2 study. JAMA Oncol 2018 January 18 (Epub ahead of print).