A case of acute myeloid leukemia with isocitrate dehydrogenase 1 (IDH1) mutation treated with combination therapy, ivosidenib and azacitidine

Abstract Background: Acute myeloid leukemia (AML) is the most common leukemia in adults, characterized by clonal proliferation of abnormal myeloid cells. Prognosis depends on factors such as age, comorbidities, performance status, and genetic mutations. Older AML patients often have limited treatment options due to poor tolerance of intensive chemotherapy, resulting in a median survival of months. Targeted therapies have improved outcomes for specific mutations, including isocitrate dehydrogenase 1 (IDH1), which occurs in 6–10% of AML cases. Ivosidenib, an IDH1 inhibitor, combined with Azacitidine, has demonstrated significant survival benefits in the phase 3 AGILE trial, with a median overall survival of 24 months versus 8 months for azacitidine monotherapy (p < 0.001). Case: A 77-year-old female with a history of stage IA invasive ductal carcinoma of the left breast (diagnosed at 73, treated with surgical resection and adjuvant hormonal therapy), hyperlipidemia, arteritis, and a 50-year history of tobacco use presented with abdominal bloating, fatigue, constipation, peripheral edema, and fluid retention. Laboratory findings included WBC 1.0 × 10³/µL, ANC 238, hemoglobin 9.6 g/dL, and platelet count 24 × 10³/µL. Peripheral smear predominantly showed lymphocytes. Bone marrow biopsy revealed 61% CD117+ myeloblasts, consistent with AML, and cytogenetics confirmed an IDH1 mutation. The patient began combination therapy with Azacitidine and Ivosidenib, completing eight cycles over six months. She tolerated treatment well, with one hospitalization for lower extremity cellulitis managed with antibiotics. She also required periodic transfusion support. A follow-up bone marrow biopsy after six months and five completed cycles showed complete remission, with hypocellularity (20–30 %) appropriate for age and normal megakaryocyte morphology with normal blast percentage. She also achieved complete hematological recovery with normalization of hemoglobin/ hematocrit, white cell count/ differential and platelet count. Conclusion: This case demonstrates the efficacy of Ivosidenib and Azacitidine in achieving remission in an older AML patient with an IDH1 mutation. As targeted therapies evolve, they provide promising alternatives for high-risk patients unable to tolerate intensive chemotherapy, improving survival