TY - JOUR
T1 - Idasanutlin plus cytarabine in relapsed or refractory acute myeloid leukemia
T2 - results of the MIRROS trial
AU - Konopleva, Marina Y.
AU - Röllig, Christoph
AU - Cavenagh, Jamie
AU - Deeren, Dries
AU - Girshova, Larisa
AU - Krauter, Jürgen
AU - Martinelli, Giovanni
AU - Montesinos, Pau
AU - Schäfer, Jonas A.
AU - Ottmann, Oliver
AU - Petrini, Mario
AU - Pigneux, Arnaud
AU - Rambaldi, Alessandro
AU - Recher, Christian
AU - Rodriguez-Veiga, Rebeca
AU - Taussig, David
AU - Vey, Norbert
AU - Yoon, Sung Soo
AU - Ott, Marion
AU - Muehlbauer, Susanne
AU - Catalani, Olivier
AU - Genevray, Magali
AU - Mundt, Kirsten
AU - Jamois, Candice
AU - Fenaux, Pierre
AU - Wei, Andrew H.
AU - Beckermann, Benjamin M.
N1 - Publisher Copyright:
© 2022 by The American Society of Hematology.
PY - 2022/7/26
Y1 - 2022/7/26
N2 - 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/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 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 = .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.
AB - 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/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 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 = .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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85134833443&partnerID=8YFLogxK
U2 - 10.1182/bloodadvances.2021006303
DO - 10.1182/bloodadvances.2021006303
M3 - Article
C2 - 35413116
AN - SCOPUS:85134833443
SN - 2473-9529
VL - 6
SP - 4147
EP - 4156
JO - Blood Advances
JF - Blood Advances
IS - 14
ER -