CPX-351 vs daunorubicin, cytarabine, and gemtuzumab ozogamicin in older adults with non–adverse-risk AML: the NCRI AML18 trial
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: ABSTRACT: We compared daunorubicin/cytarabine plus fractionated gemtuzumab ozogamicin (DAGO2) with CPX-351 (CPX; 1:2 randomization) in 439 patients with acute myeloid leukemia (AML) aged ≥60 years (median age, 68 years) without known adverse-risk cytogenetics. Median follow-up was 35 months. Patients not in measurable residual disease (MRD)-negative remission after course 1 could enter a second randomization between standard and intensified chemotherapy. Post-course 1, the overall response rate (complete remission [CR] + CR with incomplete hematological recovery) was greater after DAGO2 (60% vs 47.5%; odds ratio [OR], 0.61; P = .016). Following course 2, the overall response was not significantly different (85% for DAGO2 vs 78% for CPX; P = .095). More patients attained CR with MRD negativity after course 1 in the DAGO2 arm (47% vs 29% for CPX; OR, 0.46; P = .004). We observed better 3-year event-free survival (34% vs 27%; hazard ratio [HR], 0.73; P = .012) and overall survival (52% vs 35%; HR, 0.62; P = .001) with DAGO2. CPX did not provide a survival benefit in patients with myelodysplasia (MDS)-related mutations and was associated with poorer survival in patients with NPM1 (HR, 2.83) and FLT3 mutations (HR, 2.14). Overall, 37% of patients underwent transplantation in first remission, with no difference in transplantation frequency or survival after transplant between randomization groups. Among patients entering the course 2 randomization (n = 107), survival was equivalent between standard and intensified CPX doses (P = .565). In conclusion, in this population of older patients with AML without known adverse-risk cytogenetics, DAGO2 resulted in superior survival compared with CPX. CPX did not benefit patients with MDS-related mutations over DAGO2. This trial was registered at www.ClinicalTrials.gov as #NCT02272478.
Source: Blood
Authors: Steven Knapper, Laura W. Dillon, Malavika Babu, Abin Thomas, Ian Thomas, Christopher S. Hourigan, Georgia Andrew, Richard Dillon, Amanda Gilkes, Nuria Marquez Almuina, Sophie King, Nicholas McCarthy, Reem Bahr, Rasha W. Al-Ali, Louisa Stone, Tom Coats, Jennifer Byrne, Simone Green, Ulrik Malthe Overgaard, Rob S. Sellar, Mike Dennis, Priyanka Mehta, Robert Hills, Sylvie D. Freeman, Nigel H. Russell
Institutions: Cardiff University, Virginia Tech, National Heart, Lung, and Blood Institute, King's College London, University of Birmingham, Auckland City Hospital, Royal Devon & Exeter NHS Foundation Trust, Royal Devon University Healthcare NHS Foundation Trust, Nottingham University Hospitals NHS Trust, Castle Hill Hospital, Copenhagen University Hospital, Rigshospitalet, University College Hospital, University College London, The Christie Hospital, The Christie NHS Foundation Trust, University of Bristol, University Hospitals Bristol and Weston NHS Foundation Trust, University of Oxford, Guy's and St Thomas' NHS Foundation Trust
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,500
OpenAlex ID: W4416217098