Effect of enasidenib (ENA) plus azacitidine (AZA) on complete remission and overall response versus AZA monotherapy in mutant-IDH2 (mIDH2) newly diagnosed acute myeloid leukemia (ND-AML).

American Society of Clinical Oncology (ASCO) - Tập 38 Số 15_suppl - Trang 7501-7501 - 2020
Courtney D. DiNardo1, Andre C. Schuh2, Eytan M. Stein3, Pau Montesinos4, Andrew H. Wei5, Stéphane de Botton6, Amer M. Zeidan7, Amir T. Fathi8, Lynn Quek9, Hagop M. Kantarjian1, Mark G. Frattini10, Frederik Lersch10, Jing Gong10, Aleksandra Franovic10, Paresh Vyas11, Hartmut Döhner12
1The University of Texas MD Anderson Cancer Center, Houston, TX
2Princess Margaret Cancer Centre, Toronto, ON, Canada
3Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY
4Hospital Universitario y Politecnico la Fe, Valencia, Spain
5The Alfred Hospital and Monash University, Melbourne, Australia
6Gustave Roussy, Villejuif, France
7Yale University School of Medicine, New Haven, CT
8Massachusetts General Hospital, Harvard Medical School, Boston, MA
9Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
10Bristol-Myers Squibb, Summit, NJ
11MRC Molecular Haematology Unit and Oxford Biomedical Research Centre, University of Oxford and Oxford University Hospitals, Oxford, United Kingdom
12Universitätsklinikum Ulm, Ulm, Germany

Tóm tắt

7501 Background: ENA and AZA each induce overall response rates (ORR) of ~30% and complete remission (CR) rates of ~20% in ND-AML. In vitro, combining ENA + AZA enhances cell differentiation. We report results of the phase II portion of an open-label, randomized phase I/II study of ENA + AZA (“E+A”) vs. AZA monotherapy (“A”) in patients (pts) with m IDH2 ND-AML (NCT02677922). Methods: Pts age ≥ 18 years ineligible for intensive chemotherapy, with ECOG PS ≤ 2 and intermediate- or poor-risk cytogenetics, were randomized 2:1 to E+A or A in 28-day (d) cycles. All pts received SC AZA 75 mg/m2/d x 7 d/cycle; pts randomized to E+A also received ENA 100 mg QD. The primary endpoint was ORR (CR, CR with incomplete recovery, partial remission, morphologic leukemia-free state). Other endpoints include duration of response (DOR), overall and event-free survival (OS, EFS), safety, and m IDH2 VAF. Results: 101 pts received E+A (n = 68) or A (n = 33). Median age was 75 years (57–85); most pts (83%) had intermediate-risk cytogenetics. 21 pts in the E+A arm and 1 in the A arm were ongoing at data cutoff (Aug 2019). Most common reason for discontinuation was disease progression (E+A 31%, A 52%). Median number Tx cycles was 10 (1–26) in the E+A arm and 6 (1–28) in the A arm. 7 pts (21%) in the A arm received subsequent Tx with ENA. ORR, CR rate and DOR were significantly improved with E+A vs. A (Table). Median OS was 22 mo in both arms (HR 0.99 [95%CI 0.52, 1.87]; P = 0.97). Median EFS was 17.2 and 10.8 mo in the E+A and A arms, respectively (HR 0.59 [95%CI 0.30, 1.17]; P = 0.13). Maximal m IDH2 VAF change from BL was –83.4% with E+A vs. –17.7% with A ( P < 0.01). No baseline co-mutation predicted primary resistance. Common Tx-related grade 3–4 AEs in the E+A arm were thrombocytopenia (37%), neutropenia (35%), anemia (19%), and febrile neutropenia (15%); these occurred in 19%, 22%, 22%, and 16% in the A arm. Grade 3–4 infections occurred in 18% of E+A pts and 31% of A pts. IDH differentiation syndrome occurred in 12 pts (18%) in the E+A arm. 5 E+A pts (7%) and 1 A pt (3%) died in the first 60 d. Conclusions: Combining ENA + AZA resulted in significantly improved response rates and durations, and was generally well-tolerated in older patients with m IDH2 ND-AML. The impact of subsequent Tx on OS/EFS and new translational data will be presented at the meeting. Clinical trial information: NCT02677922 . [Table: see text]

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American Society of Clinical Oncology (ASCO)

Tập 38 Số 15_suppl

7501-7501

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