The phase 3 MIRROS (MDM2 antagonist Idasanutlin in Relapsed or Refractory acute myeloid leukemia [AML] for Overall Survival) trial (NCT02545283) evaluated the efficacy and safety of the small-molecule MDM2 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/m2 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 not met (median, 8.3 vs 9.1 months with idasanutlin-cytarabine vs placebo-cytarabine; stratified hazard ratio [HR], 1.08; 95% confidence interval [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.

Idasanutlin plus cytarabine in relapsed or refractory acute myeloid leukemia: results of the MIRROS trial / M.Y. Konopleva, C. Röllig, J. Cavenagh, D. Deeren, L. Girshova, J. Krauter, G. Martinelli, P. Montesinos, J.A. Schäfer, O. Ottmann, M. Petrini, A. Pigneux, A. Rambaldi, C. Recher, R. Rodriguez-Veiga, D. Taussig, N. Vey, S. Yoon, M. Ott, S. Muehlbauer, B.M. Beckermann, O. Catalani, M. Genevray, K. Mundt, C. Jamois, P. Fenaux, A.H. Wei. - In: BLOOD ADVANCES. - ISSN 2473-9537. - 6:14(2022 Jul 26), pp. 4147-4156. [10.1182/bloodadvances.2021006303]

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

A. Rambaldi;
2022

Abstract

The phase 3 MIRROS (MDM2 antagonist Idasanutlin in Relapsed or Refractory acute myeloid leukemia [AML] for Overall Survival) trial (NCT02545283) evaluated the efficacy and safety of the small-molecule MDM2 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/m2 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 not met (median, 8.3 vs 9.1 months with idasanutlin-cytarabine vs placebo-cytarabine; stratified hazard ratio [HR], 1.08; 95% confidence interval [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.
Adult; Antineoplastic Combined Chemotherapy Protocols; Humans; Pyrrolidines; para-Aminobenzoates; Cytarabine; Leukemia, Myeloid, Acute;
Settore MED/15 - Malattie del Sangue
18-lug-2022
Article (author)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/936409
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