Long-Term Follow-Up Affirms Ivosidenib's Sustained Benefit in IDH1-Mutated AML

This article originally appeared on Targeted Oncology^®.

New long-term follow-up data from the pivotal phase 3 AGILE trial (NCT03173248) underscore the sustained efficacy and consistent safety profile of ivosidenib (Tibsovo) in combination with azacitidine for patients with newly diagnosed isocitrate dehydrogenase 1 (IDH1)–mutated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.¹

New long-term data highlights the effectiveness and safety of ivosidenib with azacitidine for treating IDH1-mutated AML, improving patient outcomes significantly.

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The findings reinforce ivosidenib plus azacitidine as a standard of care for this patient population, addressing a critical need for improved outcomes in a historically poor-prognosis group.

The post hoc analysis, with a median follow-up of 28.6 months as of June 2022, demonstrated a significantly prolonged median overall survival (OS) in patients receiving ivosidenib and azacitidine. The median OS was 29.3 months (95% CI, 13.2–not reached) in the ivosidenib combination arm compared with 7.9 months (95% CI, 4.1–11.3) in the placebo-azacitidine arm (HR, 0.42; 95% CI, 0.27–0.65; P < .0001). This sustained survival benefit aligns with and further strengthens the results previously reported in The New England Journal of Medicine.²

Beyond overall survival, the long-term data also revealed accelerated and more durable hematologic recovery in the ivosidenib arm. A notable 53.8% of patients treated with ivosidenib achieved conversion to transfusion independence, significantly higher than the 17.1% observed in the placebo-azacitidine group (P = .0004).¹ Furthermore, molecular measurable residual disease (MRD) negativity was achieved in 30.3% (10 of 33 evaluable patients) of the ivosidenib arm by day 1 of cycle 14, all of whom had a complete response (CR). Seven of these patients achieved an MRD-negative response by day 1 of cycle 7, highlighting early and deep responses.

The safety profile of ivosidenib in combination with azacitidine remained consistent with previously published data, with no new or unexpected safety signals emerging from the long-term follow-up. The most common grade ≥3 hematologic adverse events (AEs) included anemia (26.4%), neutropenia (30.6%), and febrile neutropenia (27.8%). Among nonhematologic AEs, the most frequently reported grade ≥ 3 events were prolonged electrocardiogram QT (11.1%), pneumonia (22.2%), nausea (2.8%), hypokalemia (2.8%), and pyrexia (2.8%). These findings underscore the manageability of the therapy's safety profile in a vulnerable patient population.

The AGILE trial (NCT03173248) is a global, multicenter, double-blind, randomized, placebo-controlled phase 3 study. It was designed to assess the efficacy and safety of ivosidenib plus azacitidine vs placebo plus azacitidine in adults with previously untreated IDH1-mutated AML who were not candidates for intensive chemotherapy. The primary endpoint of the study was event-free survival, with key secondary end points including CR rate, OS, and objective response rate.

AML is a rapidly progressing cancer of the blood and bone marrow, representing the most prevalent acute leukemia in adults. Annually, approximately 20,000 new cases are diagnosed in the US and 43,000 in Europe. The incidence of AML significantly increases with age, with a median age of diagnosis at 69 years. The 5-year survival rate for AML remains challenging, at approximately 31.9%. For 6% to 10% of AML patients, a mutation in the IDH1 enzyme impedes normal blood stem cell differentiation, contributing to leukemogenesis. Targeting this specific mutation with agents like ivosidenib offers a precision medicine approach for these patients.

The US FDA granted approval to ivosidenib in combination with azacitidine for newly diagnosed IDH1-mutated AML in adults 75 years or older, or those with comorbidities precluding intensive induction chemotherapy, in May 2022.³ This approval, which came under priority review and the Real-Time Oncology Review (RTOR) pilot program, emphasized the urgency of making safe and effective treatments available to patients swiftly. These long-term results further validate the clinical utility of ivosidenib in a population that has historically faced significant challenges in treatment and prognosis.

References

1. Servier Announces Positive Data from Long-Term Follow-Up Analysis of the Phase 3 AGILE Trial of TIBSOVO® (ivosidenib) in IDH1-mutated Acute Myeloid Leukemia. Servier Pharmaceuticals. July 28, 2025. Accessed July 29, 2025. https://tinyurl.com/9aepxs3x

2. Montesinos P, Recher C, Vives S, et al. Ivosidenib and Azacitidine in IDH1-Mutated Acute Myeloid Leukemia. N Engl J Med. 2022;386:1519-1531. DOI: 10.1056/NEJMoa2117344

3. Servier announces FDA approval of Tibsovo® (ivosidenib tablets) in combination with azacitidine for patients with newly diagnosed IDH1-mutated acute myeloid leukemia. News release. Servier Pharmaceuticals. May 25, 2022. Accessed July 29, 2025. https://prn.to/3sWKYzu