Ivosidenib, as a targeted therapy for IDH1 mutant acute myeloid leukemia (AML), has clinical effects mainly in inducing differentiation, prolonging survival, and improving remission rate. The specific efficacy is affected by factors such as mutation burden and treatment line number.

1. Core treatment mechanism

(1) Targeted inhibition: selectively blocks IDH1 mutant enzyme activity, reverses epigenetic abnormalities caused by accumulation of 2-hydroxyglutarate (2-HG), and promotes differentiation and maturation of leukemia cells.

(2) Metabolic regulation: Restoring alpha ketoglutarate dependent dioxygenase function by reducing 2-HG levels, correcting abnormal methylation status of DNA and histones.

2 Key clinical data

(1) Newly diagnosed patients: The complete response rate (CR) of IDH1 mutant AML treated with monotherapy was 30.4%, with a median duration of response of 8.2 months.

(2) Relapse resistant patients: The CR+CRh (complete remission with partial hematological recovery) rate is 32.8%, with a median overall survival of 9 months, significantly better than traditional chemotherapy.

(3) Combination therapy: When used in combination with azacitidine, the CR rate of newly diagnosed AML patients reached 47.2%, with a median event free survival of 12.6 months.

3 factors affecting therapeutic efficacy

(1) Mutation characteristics: Patients with IDH1 R132C mutation have a response rate about 15% higher than other subtypes, and the duration of response is longer.

(2) The number of treatment lines: The remission rate of patients with first recurrence (41.7%) is significantly higher than that of multi line treatment failures (18.5%).

(3) Combined mutations: Patients with NPM1 mutations have better therapeutic effects, while those with FLT3-ITD mutations may reduce response rates.

4 Special Population Effects

(1) Elderly patients: The CR rate of patients aged 75 and above is comparable to that of young patients, and they have good tolerance.

(2) Secondary AML: There is no statistically significant difference in treatment efficacy compared to primary AML, and the CR rate remains in the range of 28-33%.

(3) Extramedullary lesions: show certain activity in infiltrating the central nervous system, but data is limited and further verification is needed.