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Second Primary Non-Myeloid Malignancies Following Intensive Treatment for Adult Acute Myeloid Leukaemia: A Danish Population-Based Cohort Study
20 Pages Posted: 26 Sep 2024
More...Abstract
Background: Second primary malignancies (SPMs) are a well-known, long-term complication of antineoplastic treatment. This nationwide cohort study examined the risk of non-myeloid SPMs in survivors of adult acute myeloid leukaemia (AML) treated with intensive chemotherapy and, in some cases, allogeneic stem cell transplantation (alloSCT), compared to a matched general population.
Methods: Patients with incident AML between 2000-2018, aged 18-70 years, and alive two years after intensive chemotherapy were included and matched 1:10 to comparators from the general Danish population on sex, age, and the Nordic Multimorbidity Index.
Findings: A total of 750 AML survivors and 7,500 comparators were followed for a median of 10·6 years. The hazard ratio (HR) of non-myeloid SPMs was 1·55 (95% confidence interval [CI] 1·27-1·89) for AML survivors compared to comparators, driven by non-melanoma skin cancer (HR 2·52, 95% CI 1·90-3·35), not of solid cancer (HR 1·14, 95% CI 0·87-1·49). The 10-year cumulative incidences of any non-myeloid SPM were 13·5% (95% CI 10·6-16·5%) in AML survivors and 11· 9% (95% CI 11·1-12·8%) in matched comparators. Additionally, AML survivors consolidated with alloSCT showed a trend towards a higher hazard rate of non-myeloid SPMs compared to non-transplanted AML survivors (adjusted HR 1·50, 95% CI 1·00-2·26)
.Interpretation: The increased rate of non-myeloid SPMs observed in this matched, population-based cohort study of AML survivors, treated with intensive chemotherapy with or without alloSCT, was almost entirely driven by non-melanoma skin cancer, and is thus outweighed by the importance of intensive chemotherapy.
Funding: Svend Andersen, Heinrich Kopps, and Karen Elise Jensen’s Foundation.
Declaration of Interest: Joachim Baech; Research support: Gilead Sciences Denmark. Trine Trab; Travel grant: Immedica, Research support: Janssen. Hans Beier Ommen; Consulting/advisory role: AbbVie, Bristol Myers Squibb, Jazz Pharmaceuticals, Daiichi Sankyo Nordics, and Sanofi, Research support: Jazz Pharmaceuticals. Daniel Tuyet Kristensen; Consulting/advisory role: AbbVie, Astellas Pharma, Atheneum, and Immedica, Travel grants: Swedish Orphan Biovitrum. Claudia Schöllkopf; Consulting/advisory role: Incyte. No further conflicts of interest to be reported.
Ethical Approval: This study is in accordance with the General Data Protection Regulation and is a part of North Denmark Region’s record of processing activities (F2023-111) and is approved by the Danish Clinical Registries (ALD-2023-08-01).
Keywords: Acute myeloid leukaemia, second primary non-myeloid malignancies, long-term toxicities, intensive chemotherapy, allogeneic stem-cell transplantation
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