Among patients with relapsed or refractory acute myeloid leukemia (AML), adding idasanutlin to cytarabine does not appear to improve overall survival (OS), according to research published in Blood Advances. The overall response rate (ORR) was, however, improved in the study’s experimental arm.

AML, a hematologic cancer with diverse clinical presentation and progression, is defined by the uncontrolled reproduction of myeloid blast cells. Although novel treatment strategies have improved patient outcomes over the past several decades, primary refractory rates remain around 20%, and up to 50% of patients will relapse after treatment.

Furthermore, there is currently no standard treatment regimen for patients with relapsed or refractory AML. For the randomized phase 3 MIRROS study ( Identifier: NCT02545283), researchers explored whether adding idasanutlin — a selective small-molecule MDM2 antagonist — to cytarabine would improve outcomes in this patient population.

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Overall, 355 patients were enrolled to the intent-to-treat population included in the present analysis. Of these, 232 were randomly assigned to the idasanutlin plus cytarabine group, while 123 patients were assigned to receive cytarabine only with placebo; all patients had wild-type TP53. In the experimental and placebo groups, the median ages were 63 and 62 years, respectively, 52.2% and 54.5% of patients were male sex, and 49.8% and 52.8% of patients were at first relapse at screening.

Data showed that adding idasanutlin to cytarabine did not improve OS (median, 8.3 months) compared with placebo (9.1 months; hazard ratio, 1.08; P = .58). The complete response rate, similarly, was not improved (20.3% in the idasanutlin vs 17.1% with placebo; odds ratio [OR], 1.23; 95% CI, 0.7-2.18).

ORR (38.8% vs 22% in the experimental vs placebo arms, respectively) was, however, improved (OR, 2.25; 95% CI, 1.36-3.72).

In the idasanutlin vs placebo arms, common adverse events included diarrhea (87.0% vs 32.9%, respectively), febrile neutropenia (52.8% vs 49.3%), and nausea (52.5% vs 31.5%).

Despite the improved ORR noted, the authors concluded that adding idasanutlin to cytarabine in relapsed or refractory AML is unlikely to improve clinical outcomes. They noted, however, that “further research is needed to clarify whether MDM2 inhibitors such as idasanutlin may still have a potential role in earlier-stage AML or other cancer settings.”

Disclosure: The study author(s) declared affiliations with biotech, pharmaceutical, or device companies. Please see the original reference for a full list of authors’ 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. 2022;6(14):4147-4156. doi:10.1182/bloodadvances.2021006303

This article originally appeared on Hematology Advisor