Despite survival benefits associated with newer chemotherapy regimens, survivors of classical Hodgkin lymphoma (cHL) diagnosed during their adult years continue to have significantly higher risks of all-cause mortality compared with the general population, according to results of a large population-based cohort study published in the Journal of Clinical Oncology.

In the modern era, ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) combination chemotherapy has become the preferred frontline treatment for patients with Hodgkin lymphoma in the United States. Furthermore, the use of radiotherapy (RT) in the frontline setting for the treatment of cHL has declined during the last 20 years to the extent that less than 10% of patients with early and advanced cHL in the US underwent upfront RT from 1999 to 2008.

Although the newer treatment approaches have been associated with survival gains for patients with cHL, few studies have examined the patterns of mortality of patients with cHL who have undergone more modern treatments in the frontline setting.

This study utilized data included in the Surveillance, Epidemiology, and End Results (SEER) registries for patients who were diagnosed with a first primary cHL and treated with initial chemotherapy between 2000 and 2015. Patients included in the analysis were aged 20 to 74 years.

Standard mortality ratios (SMRs), a type of relative risk, were calculated by comparing the mortality of patients with cHL with expected deaths from the general population matched according to age, sex, and calendar year; SMRs were determined separately for patients with early-stage (stage I/II) and late-stage (stage III/IV) cHL.

Of the 20,007 patients included in this analysis, 40% were diagnosed with stage III/IV cHL. At a mean follow-up of 8 years, 3380 deaths occurred, of which 59%, 31%, 9%, and 2% were attributed to lymphoma, non-cancers, other neoplasms, and unknown causes, respectively.

Compared with the general population, some of the key findings observed for patients with cHL during a follow-up period of 12 years included the following:

• SMRs for any cause-related death excluding lymphoma was 2.2 (95% CI, 95% CI, 2.0-2.4) and 1.5 (95% CI, 1.4-1.6) for patients diagnosed with late-stage and early-stage cHL, respectively.
• The SMR for non-cancer–related death was 2.4 (95% CI, 2.2-2.6) and 1.6 (95% CI, 95% CI, 1.4-1.7), for those with late- and early-stage disease, respectively.
• The SMR for death due to interstitial lung disease (ILD) was 22.1 (95% CI, 16.6-28.8) and 13.1 (95% CI, 9.2-17.9) for the groups with advanced and early-stage cHL, respectively, and this risk was highest in the year following diagnosis of cHL.
• Statistically significant SMRs for death due to benign hematologic disease, medication exposure (ie, adverse events [AEs]), and infections ranged from 3 to 10 for those with advanced disease and 2 to 3 for those with early-stage disease.
• SMRs for death due to digestive disease and heart disease were also significantly higher in both groups of patients compared with the general population.
  • SMRs for death due to heart disease in those with early- and late-stage disease were highest in the first year following disease diagnosis, but there was also evidence of an absolute increase in risk of death due to heart disease at 5 years and beyond after diagnosis of cHL.
• SMRs for death due to AEs were particularly high in patients aged 60 to 74 years at diagnosis of cHL: 73.8 (95% CI, 46.8-110.8) for those diagnosed with advanced disease and 40.3 (95% CI, 20.8-70.4) for patients with early-stage disease.
• SMRs for death due to lung cancer were 1.8 (95% CI, 1.3-2.4) and 1.4 (95% CI, 1.0-1.9) for those diagnosed with late-stage and early-stage disease, respectively.
• SMRs for death due to myelodysplastic syndrome/acute myeloid leukemia were 7.9 (95% CI, 4.6-12.7) and 4.5 (95% CI, 2.3-7.9) for those with late-stage and early-stage disease at diagnosis, respectively.

“Despite decreasing use of frontline radiotherapy, our findings among chemotherapy-treated patients diagnosed during 2000-2015 demonstrate early [ie, less than 1 year] and late increased risks of heart disease-related deaths, irrespective of cHL stage and age,” the study authors noted.

The authors noted that “patterns of excess deaths as a result of heart disease, ILD, infections, and AEs support a need for close monitoring and intervention beginning at the time of cHL diagnosis to reduce mortality for all patients, with particular attention paid to those with advanced-stage cHL and who are diagnosed at older ages.”

They further concluded that “continuing efforts are needed to develop surveillance protocols and interventions, refined treatment approaches, and new cHL therapeutics to improve patient outcomes.”

Reference

Dores GM, Curtis RE, Dalal NH, et al. Cause-specific mortality following initial chemotherapy in a population-based cohort of patients with classical Hodgkin lymphoma, 2000-2016. J Clin Oncol. Published online September 8, 2020. doi:10.1200/JCO.20.00264