Hematologic Improvements With Ivosidenib + Azacitidine Compared to Placebo + Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia

Dr. Pau Montesinos reviews the efficacy of ivosidenib and azacitidine in reducing transfusions and improving blood counts in patients with newly diagnosed acute myeloid leukemia.


  • Ivosidenib (IVO) is a potent oral targeted inhibitor of mutant isocitrate dehydrogenase 1 (mIDH1).
  • IVO plus azacitidine (AZA) significantly improved event-free survival (EFS), overall survival, and complete remission + partial hematologic recovery rates compared with placebo (PBO) + AZA in patients (pts) with newly diagnosed IDH1-mutant acute myeloid leukemia (AML) in the phase 3 AGILE trial (NCT03173248).


  • Pts were randomized 1:1 to IVO 500 mg once daily + AZA 75 mg/m2 subcutaneously or intravenously for 7 days in 28-day cycles (n = 72) or PBO+AZA (n = 74).
  • Red blood cell (RBC)/platelet transfusion history were assessed at screening and follow-up.
  • Bone marrow (BM) and peripheral blood samples were obtained at screening and during weeks 9, 17, 25, 33, 41, and 53; every 24 weeks thereafter; and at end of treatment and during EFS follow up.
  • Samples were analyzed at each local site according to ICSH guidelines.


  • In the IVO+AZA and PBO+AZA arms, 4.2% and 5.5% of pts, respectively, received concomitant granulocyte colony-stimulating factor.
  • Hemoglobin levels steadily increased from baseline at a similar rate in both treatment arms.
  • Mean platelet count recovered from baseline values in the IVO+AZA and PBO+AZA arms (71.0 and 92.6 x 109/L, respectively) as early as week 9 of treatment (171.1 and 155.1 x 109/L, respectively) and continued to steadily increase thereafter in the treated population.
  • In pts receiving IVO+AZA, mean neutrophil counts rapidly increased from baseline (0.99 x 109/L) to week 2 (2.05 x 109/L) and week 5 (4.07 x 109/L), and then generally stabilized to within the normal range to study end (last available cycle value; ̃2.0 x 109/L).
  • Mean neutrophil counts initially declined with PBO+AZA before slowly recovering to near-normal levels after 36-40 weeks.
  • The increased blood counts were accompanied by a rapid decrease in the mean BM blast percentage from 54.8% at baseline to 12.0% and 7.2% at week 9 and 17, respectively, in IVO+AZA treated patients and were maintained for 149 weeks.
  • The decline in BM blasts was slower in the PBO+AZA arm (53.7%, 34.6% and 19.6% at baseline, week 9 and week 17, respectively).
  • Among patients who were RBC/platelet transfusion-dependent at baseline (̃54.0% in both groups), 46.2% in the IVO+AZA group achieved RBC/platelet transfusion independence compared with 17.5% in the PBO+AZA arm (1-sided p = 0.0032).
  • Additionally, fewer adverse events of febrile neutropenia (28.2% vs 34.2%) and infections (28.2% vs 49.3%) were reported in the IVO+AZA arm compared to the PBO+AZA arm.


  • IVO+AZA demonstrated a significant clinical benefit compared with PBO+AZA and this sub-analysis demonstrated a rapidly improved recovery of blood counts and a reduced dependence on RBC and/or platelet transfusion.
  • Moreover, rates of febrile neutropenia and infections were reduced with IVO+AZA. Clinical trial information: NCT03173248.

Dohner H, Montesinos P, Polo SV, et al. Hematologic improvements with ivosidenib + azacitidine compared to placebo + azacitidine in patients with newly diagnosed acute myeloid leukemia. Abstract presented at: 2022 American Society of Clinical Oncology, June 3-7, 2022; Chicago, Illinois, and virtual. Abstract 7042.

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