Hematologic Improvements with Ivosidenib + Azacitidine Compared to Placebo + Azacitidine in Patients With Newly Diagnosed Acute Myeloid Leukemia
Dr. Pau Montesinos reviews the effectiveness 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 to placebo (PBO) + AZA in patients (pts) newly diagnosed HDI1-mutant acute myeloid leukemia (AML) in the phase 3 AGILE trial (NCT03173248).
- Patients were randomized 1:1 to receive 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).
- History of red blood cell (RBC)/platelet transfusion was assessed at screening and follow-up.
- Bone marrow (BM) and peripheral blood samples were collected at screening and at weeks 9, 17, 25, 33, 41, and 53; every 24 weeks thereafter; and at the end of treatment and during EFS follow-up.
- Samples were analyzed at each local site in accordance with ICSH guidelines.
- In the IVO+AZA and PBO+AZA arms, 4.2% and 5.5% of patients, respectively, received granulocyte colony-stimulating factor concurrently.
- Hemoglobin levels increased steadily from baseline at a similar rate in both treatment arms.
- The mean platelet count recovered from baseline values in the IVO+AZA and PBO+AZA arms (71.0 and 92.6 x 109/L, respectively) by the 9th week of treatment (171.1 and 155.1 x 109 /L, respectively) and continued to increase steadily thereafter in the treated population.
- In patients receiving IVO + AZA, the mean neutrophil count increased rapidly from baseline (0.99 x 109/L) to week 2 (2.05 x 109/L) and week 5 (4.07 x 109/L), then generally stabilized in the normal range until the end of the study (last cycle value available; ̃2.0 x 109/L).
- Mean neutrophil counts first decreased with PBO + AZA before slowly returning to near normal levels after 36-40 weeks.
- The increase in blood count was accompanied by a rapid decrease in the mean percentage of BM blasts from 54.8% at baseline to 12.0% and 7.2% at weeks 9 and 17, respectively, in patients treated with IVO + AZA and was 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 red blood cell/platelet transfusion dependent at baseline (̃54.0% in both groups), 46.2% in the IVO+AZA group achieved red blood cell/platelet transfusion independence versus 17.5% in the PBO+AZA arm (unilateral treatment 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.
- IVO+AZA demonstrated significant clinical benefit over PBO+AZA and this sub-analysis demonstrated rapidly improved recovery of blood counts and reduced reliance on red blood cell and/or platelet transfusion.
- Additionally, 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.