Benefits of ivosidenib regimen for IDH1-mutant AML increase with longer follow-up
Key takeaways:
- The data showed an additional 5-month increase in median OS with ivosidenib plus azacitidine.
- The combination had a safety profile consistent with earlier analyses.
CHICAGO — Ivosidenib extended median OS more than three times longer than placebo when added to azacitidine for adults with treatment-naive, IDH1-mutated acute myeloid leukemia, according to updated results of the phase 3 AGILE trial.
The long-term follow-up data, presented at ASCO Annual Meeting, showed an additional 5-month increase in median OS with the ivosidenib (Tibsovo, Servier) regimen, from 24 months to 29.3 months, as well as a greater risk reduction in deaths.
“IDH1 mutations have been explored for their connection to disease biology across various cancers, and patients with IDH1-mutated AML have historically faced a poor prognosis and limited treatment options if they are not eligible for intensive chemotherapy,” Stéphane de Botton, MD, PhD, head of drug development in acute leukemias in the department of hematology at Gustave Roussy Cancer Center, said in a Servier press release. “These updated results solidify the robust benefit of first-line treatment with Tibsovo in combination with azacitidine.”
Background, methodology
Previously reported results of the randomized, double-blind AGILE study showed the addition of ivosidenib — an oral inhibitor of mutant isocitrate dehydrogenase-1 (IDH1) — to azacitidine significantly extended EFS and OS among patients with newly diagnosed, IDH1-mutated AML. The combination also conferred higher rates of complete remission and complete remission with partial hematologic recovery compared with placebo and azacitidine.
The results served as the basis for FDA approval of the agent in May of 2022 for newly diagnosed AML.
The current analysis included 148 patients randomly assigned to 500 mg ivosidenib once daily plus azacitidine dosed at 75 mg/m2 subcutaneously or via IV for 7 days of each 28-day cycle (n = 73) or placebo plus azacitidine (n = 75).
Five patients in the placebo group crossed over to the ivosidenib group after March 2021, with no adjustment for crossover in the latest analysis.
As of June 2022, most patients had discontinued treatment, most often because of adverse events (29.1%), progression/relapse (21.6%) or patient withdrawal (10.8%). The ivosidenib group had a longer median duration of treatment than the placebo group (10.8 months vs. 3.2 months).
Median follow-up was 28.6 months.
Results, implications
The updated data showed median OS of 29.3 months (95% CI, 13.2 to not reached) with ivosidenib and azacitidine vs. 7.9 months (95% CI, 4.1-11.3) with placebo and azacitidine (HR = 0.42; 95% CI, 0.27-0.65). The ivosidenib group had longer OS rates at 12 months (62.9% vs. 38.3%) and 24 months (53.1% vs. 17.4%).
Researchers observed steady increases in hemoglobin levels from baseline until they stabilized in cycle 8. Mean platelet count recovery from baseline values occurred as early as week 8 and remained stable through week 80, according to the press release. Mean neutrophil counts increased rapidly from baseline to weeks 3 and 4, followed by stabilization within the normal range.
A significantly higher proportion of patients in the ivosidenib group converted from baseline transfusion dependence to post-baseline transfusion independence (53.8% vs. 17.1%; P = 0.0004). Fewer neutropenic fever events (27.8% vs. 33.8%) and infections (34.7% vs. 51.4%) occurred in the ivosidenib vs. placebo group. The ivosidenib group had a slightly higher discontinuation rate due to treatment-related adverse events (26.4% vs. 25.7%).
“Long-term follow-up data support the superior efficacy of [ivosidenib plus azacitidine vs. placebo plus azacitidine] in patients with newly diagnosed IDH1-mutated AML,” the poster stated.
References:
- De Botton S, et al. Abstract 7012. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
- Servier bolsters position as the leader in mutant IDH inhibition with positive new IDH1-mutated acute myeloid leukemia data at ASCO (press release). Published June 5, 2023. Accessed June 5, 2023.
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De Botton S, et al. Abstract 7012. Presented at: ASCO Annual Meeting; June 2-6, 2023; Chicago.
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