A study aimed to pinpoint the clinical characteristics of elderly patients with IDH1– or IDH2-mutated acute myeloid leukemia (AML) who had survival of two years or longer after treatment with isocitrate dehydrogenase inhibitor (IDHi) therapy. The results were presented at the Twelfth Annual Meeting of the Society of Hematologic Oncology in Houston, Texas.
“IDHi therapy can achieve long-term control of AML in a select cohort of patients, arguably ‘curing’ those in complete remission for at least five years,” wrote lead author Nilesh Kapoor, MD, of the University of Texas Southwestern Medical Center in Dallas.
This single-institution retrospective study had a cohort of nine patients aged 65 years or older at IDHi therapy initiation. The median age at diagnosis was 72 years, and 44% of the cohort was older than 75 years. In the cohort, 22% of patients had favorable-risk disease, 33% had intermediate risk, and 44% had adverse risk. Four patients had secondary AML.
Normal karyotype was found in 78% of the cohort, and the median number of mutations per patient was four. Six patients had IDH1 mutation, and three had IDH2 mutation. The most common co-occurring mutations were ASXL1, NMP1, RUNX1, and SRSF2, each of which was detected in 38% of patients, and one patient had TP53 mutation.
IDHi therapy was first-line therapy for 44% of the cohort, with one patient having received enasidenib and three having received ivosidenib plus azacitidine. It was received as second-line therapy by 33% of the cohort, with two patients having received enasidenib and one having received ivosidenib plus azacitidine and venetoclax. IDHi therapy was received as third-line therapy by 22% of the cohort, with two patients having received ivosidenib. Forty-four percent of the cohort also received maintenance IDHi therapy.
After a median follow-up of 5.5 years, the cohort had no mortalities, and its calculated five-year event-free survival rate was 89%. All patients attained complete remission, though one patient subsequently experienced relapse. IN addition, 55% of the cohort had IDH mutation clearance.
Dr. Kapoor highlighted the finding that “myelodysplastic syndrome–related gene mutations and number of mutations did not correlate with worse outcomes in our cohort,” though evaluation of other factors for use in survival prediction would require a larger study.
Reference
Kapoor N, Hoff F, Kalkan F, et al. Clinical, molecular, and treatment characteristics of long-term survivors amongst older adults with IDH1/2-mutated acute myeloid leukemia treated with IDH inhibitors. Abstract #AML-728. Presented at the Twelfth Annual Meeting of the Society of Hematologic Oncology ; September 4-7, 2024; Houston, Texas.