Adding idasanutlin to cytarabine did not improve overall survival (OS) in patients with relapsed or refractory acute myeloid leukemia (AML) in a phase 3 study.
Idasanutlin did improve the overall remission rate (ORR), but this did not translate to an improvement in OS. These results, from the phase 3 MIRROS trial, were published in Blood Advances.
The MIRROS trial (ClinicalTrials.gov identifier NCT02545283) enrolled AML patients whose disease was relapsed or refractory after 2 or fewer induction regimens or a salvage chemotherapy regimen.
The intention-to-treat (ITT) analysis included 436 patients. They were randomly assigned to receive idasanutlin at 300 mg (n=290) or placebo (n=146) orally twice daily, each in combination with cytarabine given at 1 g/m2 intravenously on days 1 to 5 of 28-day cycles.
Most patients (n=355) had wild-type TP53, including 232 patients in the idasanutlin arm and 123 in the placebo arm. The median follow-up was 6.7 months in both treatment arms.
The trial did not meet its primary endpoint of OS in the TP53 wild-type population. In this group, the median OS was 8.3 months in the idasanutlin arm and 9.1 months in the placebo arm (hazard ratio [HR], 1.08; 95% CI, 0.81-1.45; P =.58).
In the overall ITT population, the median OS was 6.8 months in the idasanutlin arm and 7.7 months in the placebo arm (HR, 1.09; 95% CI, 0.84-1.41; P =.52).
The researchers also assessed ORR — a composite of complete remission (CR), CR with incomplete blood count recovery, and CR with incomplete platelet recovery — in the TP53 wild-type population.
The ORR was significantly higher in the idasanutlin arm than in the placebo arm — 38.8% and 22.0%, respectively (odds ratio [OR], 2.25; 95% CI, 1.36-3.72; P =.008). However, there was no significant between-arm difference in the CR rate — 20.3% and 17.1%, respectively (OR, 1.23; 95% CI, 0.70-2.18; P =.408). The median duration of CR was 13.9 months and 29.4 months, respectively.
The most common any-grade adverse events (in the idasanutlin and placebo arms, respectively) were diarrhea (87.0% vs 32.9%), febrile neutropenia (52.8% vs 49.3%), and nausea (52.5% vs 31.5%). Sepsis occurred in 12.0% of patients in the idasanutlin arm and 4.8% of patients in the placebo arm.
Disclosures: This research was supported by F. Hoffmann-La Roche/Genentech. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Konopleva MY, Röllig C, Cavenagh J, et al. Idasanutlin plus cytarabine in relapsed or refractory acute myeloid leukemia: Results of the MIRROS trial. Blood Adv. Published online April 12, 2022. doi:10.1182/bloodadvances.2021006303