Servier recently published updated long-term data from the Phase 3 AGILE trial in Blood Advances, confirming the sustained survival benefit of TIBSOVO® (ivosidenib) combined with azacitidine for patients with newly diagnosed IDH1-mutated acute myeloid leukemia (AML) who cannot receive intensive chemotherapy. The findings reinforce TIBSOVO plus azacitidine as a standard of care in this population, with improved overall survival, faster hematologic recovery, and manageable safety outcomes.

Improved Survival and Hematologic Outcomes

The updated analysis, with a median follow-up of 28.6 months, showed that patients receiving the TIBSOVO-azacitidine combination had a median overall survival (OS) of 29.3 months versus 7.9 months in the placebo group. The hazard ratio was 0.42, indicating a 58% reduction in the risk of death. In addition, hematologic recovery was quicker and more sustained with TIBSOVO. Over half (53.8%) of the patients became transfusion independent, compared to only 17.1% in the control arm.

Molecular Response and Safety

Among molecular measurable-residual disease (MRD)-evaluable patients in the TIBSOVO arm, 30.3% achieved MRD negativity by Cycle 14, all with complete response (CR). By Cycle 7, 70% of these patients had already achieved MRD-negative status. The safety profile remained consistent with earlier reports. The most common Grade ≥3 blood-related side effects were anemia, neutropenia, and febrile neutropenia. Non-hematologic side effects included QT interval prolongation and pneumonia, with no new safety concerns identified.

Regulatory Background and Trial Design

TIBSOVO received FDA approval in 2022 for use in combination with azacitidine for patients 75 years or older or those unfit for intensive induction therapy. The AGILE trial was a randomized, double-blind, placebo-controlled study. Primary outcomes included event-free survival (EFS), while secondary endpoints assessed response rates and overall survival. The trial highlighted the importance of genetic testing in AML to guide targeted treatment.

Conclusion

The long-term AGILE trial results demonstrate the durable benefits of TIBSOVO in combination with azacitidine for IDH1-mutated AML patients not eligible for intensive chemotherapy. These outcomes not only support its use as a frontline therapy but also emphasize the critical role of molecular diagnostics in improving treatment selection and survival outcomes.