Long-term (74-month) efficacy and safety of ivosidenib and azacitidine in an elderly patient with mutated IDH1 acute myeloid leukemia: insights from a case report

INTRODUCTION: Older patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy (IC) are more likely to have poor outcomes. Ivosidenib is a first-in-class, oral, targeted small-molecule inhibitor of mutated isocitrate dehydrogenase (mIDH1) approved for use with azacitidine, following the AGILE trial (NCT03173248), for the treatment of mIDH1 AML in patients who are unfit for IC. CASE REPORT: We report the case of a woman diagnosed in 2019, aged 81 years, with mIDH1 AML and deemed unfit for IC due to age and comorbidities. The patient was enrolled in the AGILE trial and treated with ivosidenib and azacitidine. The patient responded well to treatment with a 1% blast count (complete response) after three cycles. At 74 months, aged 88 years, the patient was still receiving treatment with reduced doses of ivosidenib and azacitidine. The treatment was well tolerated, and the patient remained in good physical condition throughout. Mutational testing was performed throughout the trial according to protocol, with four pathogenic alterations identified at baseline (IDH1, DNMT3A splice, U2AF1, and RUNX1). Linear phylogeny was observed with the parent U2AF1 clone acquiring IDH1 followed by RUNX1. During treatment, the IDH1 and RUNX1 mutations were cleared. At a follow-up assessment, IDH1 and RUNX1 were still not detected, but ASXL1 had emerged. CONCLUSION: The exceptional 74-month long response of this patient demonstrates that a long-term response is possible for a patient unfit for IC with mIDH1 AML treated with ivosidenib and azacitidine. Further insights into the impact of the mutational status of patients and/or the clonal hierarchy are warranted.