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Nonlymphoma Mortality Following Initial Chemotherapy in Patients With Classical Hodgkin Lymphoma


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In a study reported in the Journal of Clinical Oncology, Dores et al found that patients with classical Hodgkin lymphoma continue to be at elevated risk for mortality from causes other than lymphoma, despite advances in treating this disease.

As stated by the investigators, “Mortality for patients with classical Hodgkin lymphoma 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.”

“Despite evolving classical Hodgkin lymphoma treatment approaches, patients continue to face increased nonlymphoma mortality risks from multiple, potentially preventable causes. Surveillance, early interventions, and classical Hodgkin lymphoma treatment refinements may favorably affect patient longevity, particularly among high-risk subgroups.”
— Dores et al

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Study Details

The study involved data on 20,007 patients diagnosed with stage I/II (early) or III/IV (advanced) classical Hodgkin lymphoma between age 20 and 74 who received initial chemotherapy identified from 17 SEER (Surveillance, Epidemiology, and End Results) registries during 2000 to 2015, with follow-up through 2016. Standardized mortality ratios (SMR) were used to compare cause-specific relative mortality risks following diagnosis of classical Hodgkin lymphoma to that expected in the general population, and estimated excess absolute risks (EAR; observed minus expected deaths per 10,000 patient-years) were used to determine absolute increases in risk of death.

Key Findings

At 12 years of follow-up, a total of 3,380 deaths in the classical Hodgkin lymphoma cohort were identified, including 1,321 (39%) not attributed to lymphoma.

Compared with the general population, the relative risk of death as a result of any cause other than lymphoma was increased 1.8-fold (95% confidence interval [CI] = 1.7–1.9) in the classical Hodgkin lymphoma cohort, corresponding to 39.6 excess deaths/10,000 person-years. The risk was significantly higher in individuals with advanced classical Hodgkin lymphoma (SMR = 2.2, 95% CI = 2.0–2.4, EAR = 71.7) than in those with early-stage classical Hodgkin lymphoma (SMR = 1.5, 95% CI = 1.4–1.6, EAR = 21.7, P < .001 for difference).

Deaths due to noncancer causes accounted for most nonlymphoma deaths, with the highest standardized mortality ratios increased 2.4-fold (95% CI = 2.2–2.6, EAR = 61.6) in advanced classical Hodgkin lymphoma, and 1.6-fold (95% CI = 1.4–1.7, EAR = 18.2) in early-stage classical Hodgkin lymphoma (P = .001 for difference).

Standardized mortality ratios and excess absolute risks differed by cause of death and lymphoma stage. Among the highest excess absolute risks 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 (EAR = 9.7; SMR = 22.1), and drug/medication adverse events (EAR = 7.4; SMR, 5.0) in advanced-stage classical Hodgkin lymphoma vs heart disease (EAR = 6.6; SMR = 1.7), interstitial lung disease (EAR = 3.7; SMR = 13.1), and infections (EAR = 3.1; SMR = 2.2) in early-stage classical Hodgkin lymphoma.

The highest standardized mortality ratios for interstitial lung disease, infections, and drug/medication adverse events were observed < 1 year after diagnosis of classical Hodgkin lymphoma, particularly among patients with advanced-stage disease.

Among patients with advanced-stage classical Hodgkin lymphoma, a pattern of substantially higher excess absolute risk was observed among those aged 60 to 74 for death due to heart disease, adverse events, solid neoplasms, and lung cancer.

The investigators concluded: “Despite evolving classical Hodgkin lymphoma treatment approaches, patients continue to face increased nonlymphoma mortality risks from multiple, potentially preventable causes. Surveillance, early interventions, and classical Hodgkin lymphoma treatment refinements may favorably affect patient longevity, particularly among high-risk subgroups.”

Graça M. Dores, MD, MPH, of the U.S. Food and Drug Administration, Center for Biologics Evaluation and Research, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Intramural Research Program of the National Cancer Institute and others. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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