Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood Roboz, G. J., DiNardo, C. D., Stein, E. M., de Botton, S. n., Mims, A. S., Prince, G. T., Altman, J. K., Arellano, M. L., Donnellan, W. n., Erba, H. P., Mannis, G. N., Pollyea, D. A., Stein, A. S., Uy, G. L., Watts, J. M., Fathi, A. T., Kantarjian, H. M., Tallman, M. S., Choe, S. n., Dai, D. n., Fan, B. n., Wang, H. n., Zhang, V. n., Yen, K. E., Kapsalis, S. M., Hickman, D. n., Liu, H. n., Agresta, S. V., Wu, B. n., Attar, E. C., Stone, R. M. 2019


Ivosidenib (AG-120) is an oral, targeted agent that suppresses production of the oncometabolite 2-hydroxyglutarate via inhibition of the mutant isocitrate dehydrogenase 1 (mIDH1) enzyme. From a phase 1 study of 258 patients with IDH1-mutant advanced hematologic malignancies, we report results for 34 patients with newly diagnosed acute myeloid leukemia (AML) ineligible for standard therapy who received ivosidenib 500 mg once daily. Median age was 76.5 years, 26 (76%) patients had secondary AML and 16 (47%) had received {greater than or equal to}1 hypomethylating agent for an antecedent hematologic disorder. The most common all-grade adverse events were diarrhea (n=18; 53%), fatigue (n=16; 47%), nausea (n=13; 38%), and decreased appetite (n=12; 35%). Differentiation syndrome was reported in 6 (18%) patients (grade {greater than or equal to}3 in 3 [9%]) and did not require treatment discontinuation. Complete remission (CR) + CR with partial hematologic recovery (CRh) rate was 42.4% (95% confidence interval [CI], 25.5-60.8%); CR rate was 30.3% (95% CI, 15.6-48.7%). Median durations of CR+CRh and CR were not reached, with 95% CI lower bounds of 4.6 and 4.2 months, respectively; 61.5% and 77.8% of patients remained in remission at 1 year. With median follow-up of 23.5 months (range, 0.6-40.9), median overall survival was 12.6 months (95% CI, 4.5-25.7). Of 21 (63.6%) patients who were transfusion dependent at baseline, 9 (42.9%) became transfusion independent. IDH1 mutation clearance was seen in 9/14 patients achieving CR+CRh (5/10 CR, 4/4 CRh). Ivosidenib monotherapy was well tolerated and induced durable remissions and transfusion independence in patients with newly diagnosed AML. (Trial registered at www.clinicaltrials.gov #NCT02074839.).

View details for DOI 10.1182/blood.2019002140

View details for PubMedID 31841594