Adv Ther. 2026 Feb 28. doi: 10.1007/s12325-026-03522-6. Online ahead of print.
ABSTRACT
INTRODUCTION: Olutasidenib and ivosidenib are isocitrate dehydrogenase 1 (IDH1) inhibitors approved for relapsed/refractory (R/R) IDH1 mutant (IDH1m) acute myeloid leukemia (AML).
METHODS: A matching-adjusted indirect comparison estimated relative treatment effects using registrational Phase I/II data for olutasidenib (Study 2102-HEM-101; individual patient data) and ivosidenib (Study AG120-C-001; study-level data) since a head-to-head trial is unlikely. Weights were estimated using a logistic propensity score model adjusted for pre-defined covariates identified from a literature review, validated by clinical experts. Eight covariates were determined to be the most important prognostic factors/effect modifiers for the target population as reported in the Food and Drug Administration labels: number of prior systemic therapies, age, prior hematopoietic stem cell transplantation, AML type, relapse type, cytogenetic risk, Eastern Cooperative Oncology Group performance status, and IDH1 mutation.
RESULTS: Olutasidenib versus ivosidenib adjusted rates of complete remission (CR; odds ratio [OR] 1.12, 95% confidence interval [CI] 0.61-2.08), CR plus CR with partial hematologic recovery (CR + CRh; OR 0.83, 95% CI 0.46-1.50), and median CR duration (difference in medians 11.18 months, 95% CI – 4.30 to 22.72) were not significantly different. Median CR + CRh duration was significantly longer for olutasidenib (difference in medians 9.84 months, 95% CI 3.24-22.28), accompanied by a numerical non-significant trend in overall survival that should be considered exploratory (hazard ratio 0.75, 95% CI 0.53-1.07).
CONCLUSION: While not confirmatory, these findings may be clinically relevant in the context of this difficult-to-treat R/R IDH1m AML population.
PMID:41762374 | DOI:10.1007/s12325-026-03522-6
