KEY TAKEAWAYS
- The AGILE phase III trial aimed to evaluate the long-term efficacy and safety of the ivosidenib+azacitidine combo compared to placebo and azacitidine in newly diagnosed AML pts.
- The study’s outcomes were OS, blood count recovery, transfusion independence, and safety.
- The study demonstrated superior long-term survival, hematological recovery, transfusion independence, and safety compared to placebo plus azacitidine in newly diagnosed AML pts.
The AGILE trial showed that ivosidenib plus azacitidine significantly improved event-free survival, overall survival(OS), and complete remission rates compared to placebo plus azacitidine in newly diagnosed mutant IDH1 acute myeloid leukemia (AML) patients (pts).
Researchers aimed to evaluate the long-term efficacy and safety of ivosidenib in combination with azacitidine compared to placebo and azacitidine in newly diagnosed AMLpts, utilizing follow-up data collected through June 2022.
The study administered IVO 500 mg orally once daily (or placebo) and AZA 75 mg/m2 subcutaneously or intravenously for 7 days in 28-day cycles. The evaluated outcomes were overall survival (OS), blood count recovery, transfusion independence, and safety.
The median treatment duration was (IVOAZA,n=73) – 10.8 months vs PBO-AZA (n=75) – 3.2 months. After March 2021, 5 pts crossed over from PBO-AZA to IVO-AZA; no adjustment was made for crossover in the updated OS analysis.
At a median follow-up of 28.6 months, mOS was 29.3 months (95% CI: 13.2–not reached) for IVO-AZA vs 7.9 months (95% CI: 4.1–11.3) for PBO-AZA (HR 0.42 [95% CI: 0.27–0.65]; P<0.0001). At 12 months, OS rates were 62.9% (IVO-AZA) and 38.3% (PBO-AZA); at 24 months, OS rates were 53.1% (IVO-AZA) and 17.4% (PBO-AZA).
Hemoglobin levels increased steadily from baseline (88.8 g/L) to cycle 8 in the IVO-AZA group, then stabilized. The mean platelet count recovered from 72.7×109 /L at baseline to 171.9×109 /L at week 8, then remained stable. Conversion from baseline red blood cell and/or platelet transfusion dependence to post-baseline transfusion independence was 53.8% vs 17.1% (P=0.0004) for IVO-AZA vs PBO-AZA, respectively.
Neutropenic fever events (27.8% vs 33.8%) and infections (34.7% vs 51.4%) were less common in those who received IVO-AZA vs PBO-AZA, respectively. Treatment-emergent adverse events(TRAEs) leading to treatment discontinuation occurred in 26.4% (IVO-AZA) and 25.7% (PBO-AZA) pts.
The study demonstrated superior long-term survival, hematological recovery, transfusion independence, and safety compared to placebo plus azacitidine in newly diagnosed AML pts.
Source: https://clml-soho2023.elsevierdigitaledition.com/304/index.html
Clinical Trial: https://clinicaltrials.gov/study/NCT03173248
De Botton S, Montesinos P, Vives Polo S, Zarzycka E, Wang J, Riva M, Heuser M, Calado RT, Schuh AC, Yeh SP, Hui J, Gianolio DA, Patel P, Recher C, Döhner H. Ivosidenib + Azacitidine vs Placebo + Azacitidine in Patients With Newly‑Diagnosed Acute Myeloid Leukemia: Updated Long‑term Efficacy and Safety Results From the AGILE Study.2023
