Long-Term Cause-Specific Mortality in Hodgkin Lymphoma Patients - a Nationwide Danish Cohort Study

Figure 1: Aalen Johanson cumulative incidence plot demonstrating cumulative cause specific risk of death among HL patients Background: The documented treatment-induced excess mortality in Hodgkin lymphoma (HL) has resulted in important changes in treatment regimens over the last decades, aiming at maintaining efficacy with less toxic regimens. The aim of this study was to investigate whether these changes in treatment have had a long-term effect on patterns of mortality among HL patients in a nationwide unselected cohort. Methods: The study included 1,348 Danish patients aged ≤40 years at time of HL diagnosis and treated in the years 1995–2015. Cases were followed from date of diagnosis until date of emigration, death, or until study end, whichever occurred first. The primary outcome was disease specific death due to HL, with other cause specific mortality treated as competing risk. A comparison of risk of death in the study population and national background population was performed in a landmark analysis. Results: At time of diagnosis, 66.5% of patients had Ann Arbor stage I-II; 33.5% had stage III-IV disease. After a median follow-up of 13.8 years (a total of 18,731 person-years), 139 patients (10.3%) had died with a 5-year overall survival rate of 94.6% (95% CI 93.4–95.8). Among these, 71 had died due to HL, 19 due to second malignancies, and 9 due to cardiovascular disease. Cumulative risk of death due to HL had an initial steep increase mounting to 6.1% 10 years after diagnosis, whereas the risk of death due to cardiovascular, pulmonary disease or second cancers increased at 10 years after HL diagnosis, however, only to a cumulative risk of 1.2% and 2.0%, respectively, at 20 years. By 21.6 years of follow-up risk of death due to HL was exceeded by risk of death due to other causes. We found a 6.5-fold higher risk of mortality among HL cases compared to the background population. Sub-analyses on overall and cause-specific mortality risk stratified by age, sex, disease stage, treatment period and exposure, will be presented. Conclusion: Our results show a decrease in overall risk of mortality and disease-specific mortality among HL patients exposed to contemporary treatment compared to patients from earlier treatment eras. We also find a remarkable decrease in both overall and relative risk of death due to possible treatment related late-effects. So even though excess mortality among HL patients compared to the background population persists, our results suggest that the changes in treatment strategies have led to a distinct reduction in risk of fatal long-term toxicity.