Hodgkin Lymphoma in Older Patients: An Uncommon Disease in Need of Study

ABSTRACT: Elderly Hodgkin lymphoma (HL), commonly defined as occuring in patients over 60 to 65 years of age, is an uncommon disease. In population-based studies, the proportion of HL patients over age 60 years has ranged from 15% to 30%. However, the proportion of patients over age 60 years in clinical trials has been considerably lower, typically constituting Hodgkin lymphoma (HL) is one of the most curable malignancies in adults. However, survival rates for elderly patients with HL (often defined as ≥ 60 years of age) are inferior to those achieved by younger populations. The 5-year event-free survival or freedom from treatment failure rates for elderly HL range from 30% to 40%,[1-4] with 5-year overall survival rates ranging from 40% to 55%.[2-5] This compares to 5-year event-free survival rates of > 70% to 80% and overall survival rates of > 80% to 90% for patients aged < 40 years.[1,3-5]

Suboptimal staging and inadequate treatment delivery for older patients may compromise the rate of cure.[6,7] Furthermore, comorbidities may preclude the delivery of standard chemotherapy.[8,9] Intensive treatments such as BEACOPP (bleomycin, etoposide, doxorubicin [Adriamycin], cyclophosphamide, vincristine [Oncovin], procarbazine, and prednisone) are too toxic for older HL patients,[10] while bleomycin-containing regimens including ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) are often poorly tolerated.[4,7,11-14] Treatment delivery and comorbidity do not appear to completely explain the observed differences in outcome, however, implicating the biology of HL in the elderly.[15-17]

Elderly HL has been aptly described as an orphan disease,[18] defined as a disease that affects fewer than 200,000 persons at a given time.[19] Furthermore, elderly HL is a disease for which (1) there is no agreed upon standard treatment approach; (2) it is difficult to investigate in classical trial format (due to the rarity of the disease, the advanced age of patients, and their underrepresentation in clinical trials); (3) there are large numbers of subjects who are frail or have excessive comorbidities; and (4) the approach to curative treatment is absent or inconsistent. Clinical data regarding elderly HL are derived mainly from registries and retrospective series, which have included heterogeneous patient populations. In addition, several sources of evidence suggest a different biology in patients with elderly HL.[1,15-17] An improved understanding of the epidemiology, biology, outcomes, and treatment options for elderly HL is needed.

Epidemiology

Descriptive Epidemiology

Within population-based studies, the proportion of HL patients aged 60 years or more has ranged from 15% to 30%.[1,5,13,20-22] However, the proportion of patients ≥ 60 years in clinical trials has been considerably lower, typically constituting < 5% to 10% of participants.[4,5,7]

Among two Swedish population reports from 1979 to 1988[22] and 1973 to 1994,[20] 31% and 26% of all HL patients, respectively, were ≥ 60 years. The British National Lymphoma Investigation (BNLI) compared the number of patients aged ≥ 65 years enrolled in clinical trials with the total number of older patients in their population-based cancer registry (1970–1987).[5] Approximately 15% of HL patients in the population were ≥ 65 years, whereas < 5% of patients in the same age group were entered onto BNLI trials. Investigators from the United Kingdom prospectively studied the incidence and outcomes of HL patients diagnosed between 1991 and 1998.[1,21] They reported that 20% of newly diagnosed HL patients were ≥ 60 years old. Moreover, the median overall survival of elderly HL patients was significantly inferior compared with a “normal” age- and sex-matched population (26 vs 150 months, respectively; P < .0001).

FIGURE 1

Incidence of Hodgkin Lymphoma in the United States, 2000-2005, by Age

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