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

Konopleva, Marina Y., Röllig, Christoph, Cavenagh, Jamie, Deeren, Dries, Girshova, Larisa, Krauter, Jürgen, Martinelli, Giovanni, Montesinos, Pau, Schäfer, Jonas A., Ottmann, Oliver G., Petrini, Mario, Pigneux, Arnaud, Rambaldi, Alessandro, Recher, Christian, Rodriguez-Veiga, Rebeca, Taussig, David, Vey, Norbert, Yoon, Sung-Soo, Ott, Marion Gabriele, Muehlbauer, Susanne, Beckermann, Benjamin M., Catalani, Olivier, Genevray, Magali, Mundt, Kirsten Elisabeth, Jamois, Candice, Fenaux, Pierre and Wei, Andrew H. 2022. Idasanutlin plus cytarabine in relapsed or refractory acute myeloid leukemia: results of the MIRROS trial. Blood Advances 6 (14) , pp. 4147-4156. 10.1182/bloodadvances.2021006303

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Abstract

The phase III MIRROS trial (NCT02545283) evaluated the efficacy and safety of the small-molecule MDM2 antagonist idasanutlin plus cytarabine in patients with relapsed/refractory acute myeloid leukemia (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/m2 intravenously 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 not met (median, 8.3 vs 9.1 months with idasanutlin-cytarabine vs placebo-cytarabine; stratified hazard ratio, 1.08; 95% CI, 0.81-1.45; p = .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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Additional Information: Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
Publisher: American Society of Hematology
ISSN: 2473-9529
Date of First Compliant Deposit: 20 June 2022
Date of Acceptance: 12 April 2022
Last Modified: 15 Aug 2022 14:01
URI: https://orca.cardiff.ac.uk/id/eprint/150605

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