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  3. Idasanutlin Plus Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia: Results of the MIRROS Trial.

Idasanutlin Plus Cytarabine in Relapsed or Refractory Acute Myeloid Leukemia: Results of the MIRROS Trial.

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Autores de IIS La Fe

Participantes ajenos a IIS La Fe

  • Konopleva, Marina Y.
  • Rollig, Christoph
  • Cavenagh, Jamie
  • Deeren, Dries
  • Girshova, Larisa
  • Krauter, Juergen
  • Martinelli, Giovanni
  • Schafer, Jonas A
  • Ottmann, Oliver
  • Petrini, Mario
  • Pigneux, Arnaud
  • Rambaldi, Alessandro
  • Recher, Christian
  • Taussig, David
  • Vey, Norbert
  • Yoon, Sung-Soo
  • Ott, Marion
  • Muehlbauer, Susanne
  • Beckermann, Benjamin M.
  • Catalani, Olivier
  • Genevray, Magali
  • Mundt, Kirsten
  • Jamois, Candice
  • Fenaux, Pierre
  • Wei, Andrew H.

Grupos

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.

© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.

Datos de la publicación

ISSN/ISSNe:
2473-9529, 2473-9537

Blood Advances  ELSEVIER

Tipo:
Article
Páginas:
4147-4156
PubMed:
35413116
Factor de Impacto:
2,795 SCImago ℠
Cuartil:
Q1 SCImago ℠

Citas Recibidas en Web of Science: 80

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Keywords

  • OLDER PATIENTS; AML; RECOMMENDATIONS; CLOFARABINE; MANAGEMENT; DIAGNOSIS; SURVIVAL; GENE

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