CPX-351 versus daunorubicin, cytarabine plus gemtuzumab ozogamicin in older adults with non-adverse risk AML: NCRI AML18 trial
We compared daunorubicin/AraC plus gemtuzumab (DAGO2) with CPX-351 (CPX) (1:2 randomisation) in 439 patients >60 years (median age 68 years) without known adverse-risk cytogenetics entering the NCRI AML18 version2 trial. Median follow-up was 35 months. Patients not in MRD-negative remission after course-1 could enter a second randomization between standard versus intensified chemotherapy. Post course-1 response rates were greater after DAGO2 (CR+CRi, 60% vs 47.5%, OR 0.61 95%CI 0.41-0.91, p=0.016). Following course-2 the overall response was not significantly different, 85% for DAGO2 vs 78% for CPX (OR 0.64, 95%CI 0.39-1.09, P=0.095). More patients attained CR with MRD negativity post course-1 in the DAGO2 arm (47% vs 29% for CPX, OR 0.46 95%CI 0.29-0.72, p=0.004). We observed better 3yr EFS (34% vs 27%, HR 0.73 95%CI 0.57-0.93, P=0.012) and OS (52% vs 35%, HR 0.62, 95%CI 0.46-0.83, P=0.001) with DAGO2. In a stratified analysis, CPX did not provide a survival benefit in patients with MDS-related mutations (HR 1.40, 95%CI 0.97-2.03) and was associated with poorer survival in patients with NPM1 (HR 2.83 95%CI 1.17-6.82) and FLT3 mutations (HR 2.36, 95%CI 1.10-5.07). 37% of patients were transplanted in CR1 and this did not differ by randomization nor did survival post-transplant. For patients entering the course-2 randomisation (n=107) survival was equivalent between standard versus intensified CPX doses (P=0.565). In this population of older patients, primarily with de novo AML and intermediate-risk cytogenetics DAGO2 resulted in superior survival compared to CPX including in patients with MDS-related mutations.