Cause-Specific Mortality Following Initial Chemotherapy in a Population-Based Cohort of Patients With Classical Hodgkin Lymphoma, 2000-2016

Abstract

Purpose: Mortality for patients with classical Hodgkin lymphoma (cHL) treated during an era characterized in the United States by widespread use of doxorubicin, bleomycin, vinblastine, and dacarbazine and diminishing use of radiotherapy is not well understood.

Patients and methods: We identified 20,007 individuals diagnosed with stage I/II (early) or III/IV (advanced) cHL between age 20 and 74 years treated with initial chemotherapy in US population-based cancer registries during 2000-2015 (follow-up through 2016). We used standardized mortality ratios (SMRs) to compare cause-specific relative mortality risk following cHL to that expected in the general population and estimated excess absolute risks (EARs; per 10,000 patient-years) to quantify disease-specific death burden.

Results: We identified 3,380 deaths in the cHL cohort, including 1,321 (39%) not attributed to lymphoma. Overall, noncancer SMRs were increased 2.4-fold (95% CI, 2.2 to 2.6; observed, 559; EAR, 61.6) and 1.6-fold (95% CI, 1.4 to 1.7; observed, 473; EAR, 18.2) for advanced- and early-stage cHL, respectively, compared with the general US population. SMRs and EARs differed substantially by cause of death and cHL stage. Among the highest EARs for noncancer causes of death were those for heart disease (EAR, 15.1; SMR, 2.1), infections (EAR, 10.6; SMR, 3.9), interstitial lung disease (ILD; EAR, 9.7; SMR, 22.1), and adverse events (AEs) related to medications/drugs (EAR, 7.4; SMR, 5.0) after advanced-stage cHL and heart disease (EAR, 6.6; SMR, 1.7), ILD (EAR, 3.7; SMR, 13.1), and infections (EAR, 3.1; SMR, 2.2) after early-stage cHL. Strikingly elevated SMRs for ILD, infections, and AEs were observed < 1 year after cHL. Individuals age 60-74 years with advanced-stage cHL experienced a disproportionate excess of deaths as a result of heart disease, ILD, infections, AEs, and solid tumors.

Conclusion: Despite evolving cHL treatment approaches, patients continue to face increased nonlymphoma mortality risks from multiple, potentially preventable causes. Surveillance, early interventions, and cHL treatment refinements may favorably affect patient longevity, particularly among high-risk subgroups.

FIG 1.

Flow diagram of individuals meeting inclusion criteria for the classical Hodgkin lymphoma (cHL) study population, 17 SEER cancer registry areas, 2000-2015 (followed through 2016). (*)Limited to patients with cHL who were not diagnosed by autopsy or death certificate only and patients with known age and sex.

FIG 2.

Cumulative mortality among a simulated general US population and 20,007 individuals diagnosed with cHL at ages 20-74 years and treated with initial chemotherapy: 17 SEER cancer registry areas, 2000-2015 (followed through 2016). (A-C) Cumulative mortality as a result of all causes in the general population and classical Hodgkin lymphoma (cHL) population according to age group. (D-F) Cumulative mortality as a result of lymphomas, noncancers, and other neoplasms among patients diagnosed with stage I/II cHL according to age group. (G-I) Cumulative mortality as a result of lymphomas, noncancers, and other neoplasms among patients diagnosed with stage III/IV cHL according to age group. Shaded areas (and error bars) represent the upper and lower bounds of the 95% CI for cumulative mortality.