Functional cure with single agent olutasidenib in relapsed IDH1/NPM1 co-mutated AML

Area of Science:

• Hematology
• Oncology
• Pharmacology

Background:

• Acute myeloid leukemia (AML) is a heterogeneous hematologic malignancy.
• Relapsed or refractory AML with isocitrate dehydrogenase 1 (IDH1) mutations presents a therapeutic challenge.
• Olutasidenib is an FDA-approved oral small-molecule inhibitor targeting mutant IDH1.

Purpose of the Study:

• To report the long-term outcomes of the first patient treated with olutasidenib.
• To investigate the clinical, pathological, and genomic evolution in a patient with relapsed NPM1 and IDH1 co-mutated AML treated with olutasidenib monotherapy.
• To assess minimal residual disease (MRD) in a patient achieving durable complete response.

Main Methods:

• Case report of a patient with relapsed/refractory AML receiving olutasidenib monotherapy.
• Longitudinal clinical course monitoring.
• Pathologic and genomic analysis.
• Utilized single-cell MRD assay, digital PCR, and qPCR for mutation detection (IDH1, NPM1).

Main Results:

• The patient achieved and maintained a continuous complete response (CR) for over 7 years on olutasidenib monotherapy.
• No evidence of residual detectable leukemia was found using sensitive molecular assays.
• Detailed clinical course and disease evolution were documented.

Conclusions:

• Olutasidenib monotherapy can induce durable, long-term remission in select AML patients.
• This case represents the first reported instance of a potential functional cure for AML using an IDH1 inhibitor.
• Long-term monitoring and sensitive MRD assays are crucial for evaluating treatment efficacy.