4.6 Article

Idasanutlin plus cytarabine in relapsed or refractory acute myeloid leukemia: results of the MIRROS trial

Journal

BLOOD ADVANCES
Volume 6, Issue 14, Pages 4147-4156

Publisher

ELSEVIER
DOI: 10.1182/bloodadvances.2021006303

Keywords

-

Categories

Funding

  1. F. HoffmannLa Roche Ltd.

Ask authors/readers for more resources

A study evaluating the efficacy and safety of the MDM2 antagonist idasanutlin plus cytarabine in patients with relapsed/refractory acute myeloid leukemia found that this combination did not improve overall survival or complete remission rates, despite an increased overall response rate.
The phase 3MIRROS (MDM2 antagonist Idasanutlin in Relapsed or Refractory acute myeloid leukemia [AML] for Overall Survival) trial (NCT02545283) evaluated the efficacy and safety of the small-moleculeMDM2 antagonist idasanutlin plus cytarabine in patients with relapsed/refractory (R/R) AML. Adults (n = 447) with R/R AML whose disease relapsed or was refractory after <= 2 prior induction regimens as initial treatment or following salvage chemotherapy regimen, with Eastern Cooperative Oncology Group performance status <= 2 were enrolled regardless of TP53 mutation status and randomly assigned 2:1 to idasanutlin 300 mg or placebo orally twice daily plus cytarabine 1 g/m(2) IV on days 1 to 5 of 28-day cycles. At primary analysis (cutoff, November 2019), 436 patients were enrolled, including 355 in the TP53 wild-type intention-to-treat (TP53WT-ITT) population. The primary endpoint, overall survival in the TP53WT-ITT population, was notmet (median, 8.3 vs 9.1months with idasanutlin-cytarabine vs placebo-cytarabine; stratified hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.81-1.45; P 5.58). The complete remission (CR) rate, a key secondary endpoint, was 20.3% vs 17.1% (odds ratio [OR], 1.23; 95% CI, 0.70-2.18). The overall response rate (ORR) was 38.8% vs 22.0% (OR, 2.25; 95% CI, 1.36-3.72). Common any-grade adverse events (>= 10% incidence in any arm) were diarrhea (87.0% vs 32.9%), febrile neutropenia (52.8% vs 49.3%), and nausea (52.5% vs 31.5%). In summary, despite improved ORR, adding idasanutlin to cytarabine did not improve overall survival or CR rates in patients with R/R AML.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.6
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available