CPX-351 vs daunorubicin, cytarabine, and gemtuzumab ozogamicin in older adults with non–adverse-risk AML: the NCRI AML18 trial

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.

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Publication Details

Journal
Blood
Published
2025-11-14
DOI
https://doi.org/10.1182/blood.2025031006
Citations
2
Primary Topic
Acute Myeloid Leukemia Research
Type
article
Field-Weighted Citation Impact
3.54

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article

CPX-351 vs daunorubicin, cytarabine, and gemtuzumab ozogamicin in older adults with non–adverse-risk AML: the NCRI AML18 trial

Richard Dillon, Steven Knapper, Simone Green, Ian Thomas et al.
2 citations
Blood
Acute Myeloid Leukemia Research
3.54
article

CPX-351 vs daunorubicin, cytarabine, and gemtuzumab ozogamicin in older adults with non–adverse-risk AML: the NCRI AML18 trial

Richard Dillon, Steven Knapper, Simone Green, Ian Thomas, Abin Thomas, Malavika Babu, Thomas Coats, Amanda Gilkes, Louisa Stone, Sylvie Freeman, Rob S. Sellar, Nigel H. Russell, Robert K. Hills, Mike Dennis, Priyanka Mehta, Georgia Andrew, Laura W. Dillon, Christopher Simon Hourigan, Ulrik Malthe Overgaard, Jenny Byrne, Sophie King, Reem Bahr, Nicholas McCarthy, Nuria Marquez-Almuina, Rasha W Al-Ali
article en
2 citations

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.

BloodVol. 147(10)
University College Hospital (GB), North Bristol NHS Trust (GB), Nottingham University Hospitals NHS Trust (GB), King's College - North Carolina (US), King's College London (GB), Guy's and St Thomas' NHS Foundation Trust (GB), Royal Devon & Exeter NHS Foundation Trust (GB), University Hospitals Bristol NHS Foundation Trust (GB), Castle Hill Hospital (GB), Auckland City Hospital (NZ), Copenhagen University Hospital (DK), Rigshospitalet (DK), University of Oxford (GB), National Heart, Lung, and Blood Institute (US), Cancer Research Center (US), The Christie Hospital (GB), The Christie NHS Foundation Trust (GB), Biomedical Research Institute (US), University Hospitals Bristol and Weston NHS Foundation Trust (GB), University College London (GB), Cardiff University (GB), University of Birmingham (GB), Cardiff Metropolitan University (GB)
Amgen, Bristol-Myers Squibb, Pfizer, AstraZeneca, Celgene, National Cancer Research Institute, Jazz Pharmaceuticals, Cancer Research UK, Astellas Pharma, Servier, Daiichi Sankyo Europe
Openalex Percentile: Top 6%
Acute Myeloid Leukemia Research
3.54
DOIOpen Access PDFOpenAlex
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