Population-based cohort study of second primary non-myeloid malignancies following intensive treatment for adult myeloid leukemia

Second primary malignancies (SPMs) are a long-term complication of antineoplastic treatment. A nationwide cohort study in Denmark examined the risk of non-myeloid SPMs in survivors of adult acute myeloid leukemia (AML) treated with intensive chemotherapy. The study included 750 AML survivors between 2000 and 2018, alive and aged 18-70 years two years after start of intensive chemotherapy, matched 1:10 to comparators from the general Danish population on sex, age, and multimorbidity (n=7500). The median duration of follow-up was 10.6 years. The risk of non-myeloid SPMs was higher among survivors than among comparators (HR 1.55; 95% CI 1.27-1.89), driven by non-melanoma skin cancer (2.52; 1.90-3.35) but not by solid cancer (1.14; 0.87-1.49). The 10-year cumulative incidences of any non-myeloid SPM were 13.5% (95% CI 10.6-16.5) among AML survivors and 11.9% (11.1-12.8) among comparators. AML survivors consolidated with alloSCT had a higher rate of non-myeloid SPMS compared to non-transplanted AML survivors (aHR 1.50; 95% CI 1.00-2.26). The authors conclude that the increased rate of non-myeloid SPMs observed in this study was almost entirely driven by non-melanoma skin cancer and is thus outweighted by the importance of intensive chemotherapy.