Upped Risk of Death From Other Causes After Hodgkin Lymphoma

Roxanne Nelson, RN, BSN

October 27, 2020

Classic Hodgkin lymphoma (cHL) is now a highly curable disease, but survivors face an increased risk of death from causes other than lymphoma, a new study reports.

At 12 years of follow-up, all-cause mortality for cHL survivors was significantly higher than the general population, and the cumulative mortality attributed to noncancer causes comprised a substantial proportion of total deaths. This was especially prevalent, the researchers noted, among patients diagnosed between the ages of 45-74 years.

"Patterns of excess deaths as a result of heart disease, interstitial lung disease, infections, and adverse events 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 those who are diagnosed at older ages," write the authors.

The study was published online in the Journal of Clinical Oncology.

Led by Graça M. Dores, MD, of the Division of Epidemiology, Center for Biologics Evaluation and Research, US Food and Drug Administration, the authors sought to assess mortality risks among individuals diagnosed with cHL in 2000-2015. During that period, use of radiotherapy declined and patients would have been treated with chemotherapy dominated by use of doxorubicin, bleomycin, vinblastine, and dacarbazine, they note.  

Using data from the SEER registry, the team identified 20,007 individuals aged 20-74 years diagnosed with cHL during the study period. Of this group, 40% had stage III/IV cHL, and 32% were 10-year survivors.

Standardized mortality ratios (SMRs) were used to compare cause-specific relative mortality risk following cHL to the mortality expected in the general population. Excess absolute risk (EAR; per 10,000 patient-years) was used to estimate disease-specific death burden.

High Rate of Noncancer Deaths

Among the 20,007 patients with cHL, there were 3380 deaths, of which 59% (n = 1978) were attributed to lymphoma, 31% (n = 1032) to noncancer causes, 9% (n = 289) to other cancer types, and 2% (n = 81) were unknown. All-cause mortality occurred disproportionately among men (62%), patients with nodular sclerosis subtype (52%), and those who received initial chemotherapy alone (80%).

At 12 years of follow-up, mortality for the cHL cohort exceeded that for the general population in the three age groups studied. In those aged 20-44 years at diagnosis, cumulative mortality rate of lymphoma deaths (stage I/II, 5.2%; stage III/IV, 12.9%) exceeded that of noncancer deaths (stage I/II, 2.0%; stage III/IV, 4.0%) at 12 years, regardless of cancer stage.

Among patients aged 45-59 and 60-74 years at early stage cHL diagnosis, lymphoma and noncancer deaths were generally similar, but among advanced-stage disease, lymphoma deaths (aged 45-59, 19.3%; aged 60-74, 34.6%) exceeded noncancer deaths (aged 45-59, 13.1%; aged 60-74, 22.4%) over the 12-year period.

Compared with the general population, the relative risk of death from any cause other than lymphoma was increased 1.8-fold among patients with cHL, which extrapolates to 39.6 excess deaths/10,000 person-years. The risk was significantly higher in those with advanced disease (SMR, 2.2; EAR, 71.7) versus early stage cHL (SMR, 1.5; EAR, 21.7; P difference < .001). The risks were lower among younger patients treated with initial chemotherapy and radiotherapy.

SMRs and EARs differed substantially by cHL stage at diagnosis and cause of death. Among the highest EARs for noncancer mortality in the group with advanced stage disease 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 adverse events related to drugs or medications (EAR, 7.4; SMR, 5.0).

Among the group with early stage cHL, the greatest causes of noncancer mortality were 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).

Longer-Term Follow-Up Needed

Survival after CHL is high, experts note in an accompanying editorial. Andrew M. Evens, DO, Rutgers Cancer Institute of New Jersey, New Brunswick, and Susan K. Parsons, MD, Tufts University School of Medicine, Boston, Massachusetts, emphasize the success of front-line treatment as well as the ability to salvage most patients with cHL after disease recurrence.

However, survival often comes at a cost in terms of post-acute morbidity and late effects, which in turn, can affect the quality and length of survivorship, they write. "Analyses such as the current report underscore the continuing risks for patients, including in the modern era, and with events beginning within 1 year."

The editorialists add that cHL clinical trials should invest in longer-term follow-up and more detailed analyses of morbidity after active treatment is completed.

The study was supported by the Intramural Research Program, National Cancer Institute. The authors have reported no relevant financial relationships. Both editorialists report relationships with pharmaceutical companies, Evens with Seattle Genetics, Pharmacyclics, Verastem, Miltenyi Biotec, Epizyme, Novartis, MorphoSys, Cota Healthcare, Affimed Therapeutics, Bayer, Tesaro, and Research to Practice, and Parsons with Seattle Genetics.

J Clin Oncol. Published online September 18, 2020. Abstract, Editorial

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