KEY TAKEAWAYS
- The AGILE phase 3 aimed to evaluate myelosuppression recovery in ND-mutant IDH1 AML patients ineligible for IC IVO+AZA.
- The result concluded that IVO+AZA for ND AML offers rapid neutrophil recovery and reduced hospitalization time.
Hypomethylating agent (HMA)-based treatments for Acute Myeloid Leukemia (AML) ineligible for intensive chemotherapy often lead to severe and prolonged myelosuppression. The past finding (Rausch et al. Cancer. 2021;127:2489) suggests that among the 64 newly-diagnosed responders to venetoclax plus HMA, during the induction period, the median time to absolute neutrophil count recovery ≥0.5×109/L was 34 days (range to ≥1.0, 19-129 days), and the median hospitalization duration was 32 days (range, 8-62), exceeding 100% of induction days.
Herein, Amir T. Fathi and his research group investigated the combination of Ivosidenib (IVO) and Azacitidine (AZA) in patients with newly diagnosed mutant IDH1 AML ineligible for intensive chemotherapy.
In the double-blind phase 3 study 28-day cycle, patients were administered IVO (or placebo) along with AZA, and the use of colony-stimulating factor (CSF) was determined by the investigator’s discretion. Absolute neutrophil count (ANC) assessments were conducted weekly during Cycle 1 and biweekly during Cycle 2-4, followed by per-cycle evaluations. Hospitalization days were recorded and calculated per day alive throughout the study.
The result showed that the event-free survival hazard ratio was 0.33 (P=0.002), favoring IVO+AZA over PBO+AZA. The baseline median ANC was 0.2×109/L in both arms. With IVO+AZA (n=71), median ANC increased to 0.9×109/L by C1 day 15, sustained between 1.3-2.0×109/L days 21-365 (with one excursion to 1.0×109/L at week 10), and thereafter maintained between 1.3-2.3×109/L. This ANC recovery was significantly more rapid vs.
PBO+AZA (n=73) (P<0.025 for C1D15C8), where ANC remained <0.5×109/L until C4, <1.0×109/L through C8, and without two consecutive readings >1.0×109/L until C15. CSF use (25.4% vs. 30.1%) and neutropenic fever (28.2% vs. 34.2%) were similar; infections were reduced with IVO+AZA (28.2% vs. 49.3%, relative risk 0.57; CI, 0.37-0.89). Hospital days during Days 1-28 averaged 42.9% vs. 33.7% of days alive for IVO+AZA vs. PBO+AZA, respectively, and during Days 1-90 averaged 30.9% vs. 33.9% of days alive.
Researchers concluded that individuals undergoing IVO+AZA treatment for ND AML demonstrated consistent and rapid recovery of neutrophil levels. Conversely, patients receiving AZA alone experienced prolonged and severe neutropenia lasting up to 12 months. The hospitalization rates, initially around 35-40% of days alive in the first cycle, showed improvement to approximately 30% in cycles 1-3 for both treatment arms. These safety benefits align with the efficacy advantages observed with IVO+AZA therapy.
This study is sponsored by Institut de Recherches Internationales Servier
Source: https://clml-soho2023.elsevierdigitaledition.com/302/index.html
Clinical Trial: https://clinicaltrials.gov/study/NCT03173248
Fathi AT, Smith BD, Angiolillo A, et al. “Time to Resolution of Myelosuppression and Associated Hospitalization in Patients With Newly‑Diagnosed Acute Myeloid Leukemia (AML) Treated With Ivosidenib (IVO) + Azacitidine (AZA) Compared to Placebo (PBO) + AZA”. Presented at SOHO 2023. (Abstract: AML-446).
