30May

Effect of enasidenib plus azacitidine (AZA) on Complete and overall response versus AZA monotherapy in mutant-IDH2 newly diagnosed AML

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)


Abstract No : 7501

Abstract Type : Poster Discussion Session

Indication : Acute Myeloid Leukemia             

Intervention : AG-120; AG-221

Company : BMS

Technology : Small molecule


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 mIDH2 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.


Conclusion:

Combining ENA + AZA resulted in significantly improved response rates and durations, and was generally well-tolerated in older patients with mIDH2 ND-AML. The impact of subsequent Tx on OS/EFS and new translational data will be presented at the meeting.


Commentary:

Combination of targeted suppression of mIDH2 and anti-leukemia effects of AG120 and Azacitidine significantly increase ORR: 71%(53% CR) vs 42%(12% CR).


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