Long-term remission and survival in older adults with IDH-mutated acute myeloid leukemia treated with IDH inhibitors.

BACKGROUND

Isocitrate dehydrogenase inhibitors (IDHi) for IDH-mutated acute myeloid leukemia (AML) are important treatment options for older adults in whom treatment-related toxicities are a major concern. Long-term data on IDHi are limited.

METHODS

We conducted a single-center retrospective study of patients aged ≥ 65 years with newly diagnosed or relapsed/refractory IDH-mutated AML who received ivosidenib or enasidenib for ≥ 2 continuous years and either achieved complete remission (CR) or initiated therapy in CR as maintenance.

RESULTS

Nine patients were identified with median treatment duration of 6.88 years (range: 1.94-8.87). Median age at IDHi initiation was 71 years (range: 65-84); 44% were ≥ 75 years. Six patients (67%) had IDH1 mutations and 3 (33%) had IDH2 mutations. Median number of mutated genes per patient was 4 (range: 1-6). There were no mutations in the receptor tyrosine kinase pathway. Four patients began IDHi at diagnosis, 3 upon relapse, and 2 as maintenance following first CR. No differentiation syndrome occurred. Seven patients (78%) remain on IDHi and in CR; both who relapsed had antecedent myeloid neoplasms. At median follow-up of 6.88 years (range: 2.62-8.87), median event-free survival (EFS) and overall survival (OS) were not reached. Five-year EFS and OS were 78% (95% CI: 55-100) and 88% (95% CI: 67-100), respectively.

CONCLUSIONS

This selected real-world cohort demonstrates durable responses exceeding published benchmarks and has one of the longest follow-up periods reported for IDHi in AML. A subset of older adults with IDH-mutated AML can achieve highly durable remissions on IDHi without significant toxicity.