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. 2024 Dec 30:50:101204.
doi: 10.1016/j.lanepe.2024.101204. eCollection 2025 Mar.

Second primary non-myeloid malignancies following intensive treatment for adult acute myeloid leukaemia: a Danish population-based cohort study

Nanna Nørtoft Nielsen  1 , Jonas Faartoft Jensen  1 , Joachim Baech  1 , Trine Trab  1   2   3 , Tarec Christoffer El-Galaly  1   4   5 , Claudia Schöllkopf  2   6 , Andreas Due Ørskov  7 , Hans Beier Ommen  8 , Lene Sofie Granfeldt  5 , Daniel Tuyet Kristensen  1   4 , Marianne Tang Severinsen  1   4
Affiliations

Second primary non-myeloid malignancies following intensive treatment for adult acute myeloid leukaemia: a Danish population-based cohort study

Nanna Nørtoft Nielsen et al. Lancet Reg Health Eur. .

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 and 2018, alive and aged 18-70 years two years after start of intensive chemotherapy, were included and matched 1:10 to comparators from the general Danish population on sex, age, and the Nordic Multimorbidity Index. Exclusion criteria were non-myeloid SPMs for both AML survivors and comparators.

Findings: A total of 750 AML survivors and 7500 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 had 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 population-based cohort study of AML survivors 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.

Keywords: Acute myeloid leukaemia; Allogeneic stem-cell transplantation; Intensive chemotherapy; Long-term toxicities; Second primary non-myeloid malignancies.

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Conflict of interest statement

JB has received research support from Gilead Sciences Denmark. TT has received travel grant from Immedica and research support from Janssen. HBO has a consulting/advisory role for Abbvie, Bristol Myers Squibb, Daiichi Sankyo Nordics, Celgene, and Sanofi and has received research support from Jazz Pharmaceuticals and a travel grant from Beigene. DTK has a consulting/advisory role for AbbVie, Astellas Pharma, Atheneum, and Immedica and has received travel grants from Swedish Orphan Biovitrum. CS has a consulting/advisory role for Incyte and has received a travel grant from Abbvie, Norton Healthcare Limited and Swedish Orphan biovitrum. No further conflicts of interest to be reported.

Figures

Fig. 1
Fig. 1
CONSORT diagram of the study population. Inclusion of patients with AML, who were alive two years after receiving intensive induction chemotherapy, and matched comparators from the general population, and further stratification of AML survivors additionally treated with alloSCT before index.1 At index’ is equivalent to the time of inclusion two years after the date of initiation of induction chemotherapy. 2Includes patients receiving alloSCT for previous haematological malignancies and patients not registered with a valid type of intensive treatment for AML. Abbreviations: AlloSCT, allogeneic stem cell transplantation; AML, acute myeloid leukaemia; NMI, nordic multimorbidity index.
Fig. 2
Fig. 2
Cumulative incidences of non-myeloid SPMs in AML survivors, alive two years after initiation of intensive induction chemotherapy, and matched comparators, with death as a competing event. (a) Cumulative incidence of any type of non-myeloid SPM. (b) Cumulative incidence of solid cancers. (c) Cumulative incidence of NMSCs. (d) Cumulative incidences of non-myeloid haematological malignancies. Abbreviations: AML, acute myeloid leukaemia; NMSC, non-melanoma skin cancer; SPM, second primary malignancy.
Fig. 3
Fig. 3
Cumulative incidences of SPMs, with death as a competing event, in AML survivors treated with alloSCT in addition to intensive chemotherapy compared to matched comparators, and in non-transplanted AML survivors compared to matched comparators. AML patients were alive and cancer free two years after initiation of induction chemotherapy. (a) Cumulative incidence of any type of non-myeloid SPM in non-transplanted AML survivors and their matched comparators. (b) Cumulative incidence of any type of non-myeloid SPM in AML survivors treated with alloSCT and their matched comparators. (c) Cumulative incidence of solid cancers in non-transplanted AML survivors and their matched comparators. (d) Cumulative incidence of solid cancers in AML survivors treated with alloSCT and their matched comparators. (e) Cumulative incidence of NMSC in non-transplanted AML survivors and their matched comparators. (f) Cumulative incidence of NMSC in AML survivors treated with alloSCT and their matched comparators. Abbreviations: AlloSCT, allogeneic stem cell transplantation; AML, acute myeloid leukaemia; NMSC, non-melanoma skin cancer; SPM, second primary malignancy.
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