CPX-351 versus daunorubicin, cytarabine plus gemtuzumab ozogamicin in older adults with non-adverse risk AML: NCRI AML18 trial

Knapper, Steven ORCID: https://orcid.org/0000-0002-6405-4441, Dillon, Laura W., Babu, Malavika, Thomas, Abin ORCID: https://orcid.org/0000-0002-8283-6762, Thomas, Ian, Hourigan, Christopher S, Andrew, Georgia, Dillon, Richard, Gilkes, Amanda, Marquez Almuina, Nuria, King, Sophie, McCarthy, Nicholas, Bahr, Reem, Al-Ali, Rasha W, Stone, Louisa, Coats, Tom, Byrne, Jennifer, Green, Simone, Overgaard, Ulrik Malthe, Sellar, Rob S., Dennis, Mike, Mehta, Priyanka, Hills, Robert, Freeman, Sylvie D. and Russell, Nigel H 2025. CPX-351 versus daunorubicin, cytarabine plus gemtuzumab ozogamicin in older adults with non-adverse risk AML: NCRI AML18 trial. Blood 10.1182/blood.2025031006

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Abstract

We compared daunorubicin/AraC plus fractionated gemtuzumab (DAGO2) with CPX-351 (CPX) (1:2 randomisation) in 439 patients ≥60yrs (median age 68yrs) without known adverse-risk cytogenetics entering the NCRI AML18 version2 trial (NCT02272478). 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 2.14, 95%CI 0.98-4.68). 37% of patients were transplanted in CR1 and this did not differ by randomization. Survival post-transplant did not differ between arms. 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 without known adverse-risk cytogenetics, DAGO2 resulted in superior survival compared to CPX. CPX did not benefit those with MDS-related mutations over DAGO2.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine Research Institutes & Centres > Centre for Trials Research (CNTRR)
Additional Information:	License information from Publisher: LICENSE 1: URL: http://creativecommons.org/licenses/by-nc-nd/4.0/, Start Date: 2025-11-20
Publisher:	American Society of Hematology (ASH Publications)
ISSN:	0006-4971
Date of First Compliant Deposit:	25 November 2025
Date of Acceptance:	16 October 2025
Last Modified:	25 Nov 2025 12:15
URI:	https://orca.cardiff.ac.uk/id/eprint/182641

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