KEY TAKEAWAYS
- The MIRROS trial is a phase 3 study evaluating the efficacy and safety of idasanutlin plus cytarabine in patients with relapsed/refractory AML.
- The primary aim was to assess the overall survival in the TP53 wild-type intention-to-treat population.
- Although the overall response rate was improved, adding idasanutlin to cytarabine did not improve OS or complete remission rates in patients with relapsed/refractory AML.
The small-molecule MDM2 antagonist idasanutlin plus cytarabine was tested for efficacy and safety in patients with relapsed/refractory (R/R) in the phase 3 MIRROS (MDM2 antagonist Idasanutlin in Relapsed or Refractory acute myeloid AML [AML] for Overall Survival) experiment (NCT02545283). Without regard to TP53 mutation status, adults (n = 447) with R/R AML who had disease relapse or was refractory after 2 prior induction regimens as initial treatment or following salvage chemotherapy regimen were enrolled and randomly assigned 2:1 to receive either idasanutlin 300 mg or placebo orally twice daily plus cytarabine 1 g/m2 IV on days 1 to 5 of 28-day cycles.
At the time of the primary analysis (November 2019), 355 patients were included in the TP53 wild-type intention-to-treat (WT-ITT) population of 436 enrolled patients. Overall survival in the TP53WT-ITT population was not reached (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). Twenty-three per cent versus seventeen per cent of patients achieved complete remission (CR; OR, 1.23; 95% CI, 0.70-2.18). CR is an important secondary goal. The odds ratio (OR) was 2.25 (95% CI, 1.36-3.72) for a positive response (ORR) of 38.8% versus 22.0%. Diarrhea (87.0%), febrile neutropenia (52.8%), and nausea (52.5%) were the most common any-grade adverse events (10% incidence in any arm). Overall survival and CR rates were not improved in patients with R/R AML when idasanutlin was added to cytarabine, even though the ORR was improved.
Source: https://pubmed.ncbi.nlm.nih.gov/35413116/
Clinical Trial: https://clinicaltrials.gov/ct2/show/NCT02545283
Konopleva MY, Röllig C, Cavenagh J, Deeren D, Girshova L, Krauter J, Martinelli G, Montesinos P, Schäfer JA, Ottmann O, Petrini M, Pigneux A, Rambaldi A, Recher C, Rodriguez-Veiga R, Taussig D, Vey N, Yoon SS, Ott M, Muehlbauer S, Beckermann BM, Catalani O, Genevray M, Mundt K, Jamois C, Fenaux P, Wei AH. Idasanutlin plus cytarabine in relapsed or refractory acute myeloid leukemia: results of the MIRROS trial. Blood Adv. 2022 Jul 26;6(14):4147-4156. doi: 10.1182/bloodadvances.2021006303. PMID: 35413116; PMCID: PMC9327534.
