CPX-351 vs daunorubicin, cytarabine, and gemtuzumab ozogamicin in older adults with non–adverse-risk AML: the NCRI AML18 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.
Article Details
Authors (25)
Steven Knapper
School of Medicine, Cardiff University, Cardiff, United Kingdom
Laura W. Dillon
1Fralin Biomedical Research Institute, Virginia Tech Fralin Biomedical Research Institute Cancer Research Center, Washington, DC
Malavika Babu
Abin Thomas
Ian Thomas
Cardiff University, Cardiff, United Kingdom
Christopher S. Hourigan
1Fralin Biomedical Research Institute, Virginia Tech Fralin Biomedical Research Institute Cancer Research Center, Washington, DC
Georgia Andrew
4Laboratory of Myeloid Malignancies, National Heart, Lung, and Blood Institute, Bethesda, MD
Richard Dillon
5King's College London, London, United Kingdom
Amanda Gilkes
42Department of Haematology, University of Cardiff, Cardiff, United Kingdom
Nuria Marquez Almuina
3Centre for Trials Research, Cardiff University, Cardiff, United Kingdom
Sophie King
Centre for Trials Research,Cardiff University, Cardiff, United Kingdom
Nicholas McCarthy
6Department of Clinical Immunology Service, School of Infection, Inflammation and Immunology, University of Birmingham College of Medicine and Health, Birmingham, United Kingdom
Reem Bahr
2Fralin Biomedical Research Institute, Virginia Tech Fralin Biomedical Research Institute, Cancer Research Center, Washington, DC
Rasha W. Al-Ali
2Fralin Biomedical Research Institute, Virginia Tech Fralin Biomedical Research Institute, Cancer Research Center, Washington, DC
Louisa Stone
7Clinical Haematology, Auckland City Hospital, Auckland, New Zealand
Tom Coats
8Department of Clinical Haematology, Royal Devon and Exeter NHS Foundation Trust, Exeter, United Kingdom
Jennifer Byrne
Simone Green
Castle Hill Hospital, Hull, United Kingdom
Ulrik Malthe Overgaard
Copenhagen University Hospital, Copenhagen, Denmark
Rob S. Sellar
University College London, London, United Kingdom
Mike Dennis
The Christie NHS, Manchester, United Kingdom
Priyanka Mehta
University Hospitals Bristol and Weston NHS Trust, Bristol, United Kingdom
Robert Hills
15Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
Sylvie D. Freeman
47School of Infection, Inflammation and Immunology, University of Birmingham College of Medicine and Health, Birmingham, United Kingdom
Nigel H. Russell
Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom