Safety and efficacy of ivosidenib in the treatment of isocitrate dehydrogenase 1 mutant cholangiocarcinoma and acute myeloid leukemia: a systematic review and meta-analysis

Isocitrate dehydrogenase 1 (IDH1) mutations have gained interest because of their association with malignancies, including cholangiocarcinoma and acute myeloid leukemia. Ivosidenib, an inhibitor of IDH1 mutations, inhibits the formation of the oncometabolite D-2-HG, restoring normal cellular turnover and inhibiting tumorigenesis. In July 2024, a literature search was done using these databases: PubMed, Cochrane Library, and Embase. Studies were to show the safety and efficacy of ivosidenib using 95% confidence intervals (CIs). Preferred Reporting Items for Systematic reviews and Meta-Analyses flow guidelines were followed. Four articles involving 533 patients were included. The objective response rate (ORR) and progression-free survival (PFS) were significantly improved in the control group where risk ratio was 0.79, 95% CI: 0.71–0.89, Z = 4.05, a P value less than 0.001 for PFS, and odds ratio was 0.45, 95% CI: 0.30–0.68, Z value of 3.86, and P = 0.001 for ORR. The safety profile was favorable. Overall survival (OS) did not change significantly within the groups, as indicated by a P value of 0.78, risk ratio of 0.98, 95% CI: 0.83–1.15, and Z = 0.27. Ivosidenib demonstrated a PFS advantage and improved ORR with a favorable safety profile, but no effect on the OS. Evidence is suggestive of its plausibility for clinical usage as an adjunct therapy.