How Can Outcomes Be Improved for Older Patients With Hodgkin Lymphoma

Older age has consistently been identified as an independent adverse prognostic factor for Hodgkin lymphoma (HL) survival in population-based studies and clinical trials in the last several decades. In the 1970s and 1980s, 5-year event-free survival or freedom from treatment failure rates for older (or elderly) patients with HL, most commonly defined as age 60 years, ranged from 30% to 40% with 5-year overall survival (OS) rates of 40% to 50%. These rates are markedly inferior compared with patients with HL younger than age 60 years with 5-year event-free survival of 70% to 75% and OS greater than 80% to 85%. An important question is: have outcomes improved for older patients with HL with refined therapeutic regimens and enhanced supportive care measures in the contemporary era? In a 2008 SEER database analysis, Brenner et al reported improved HL survival over time across all age groups, including older patients. The 5-year survival rates for patients age 60 years increased from 1980 to 1984 through 2000 to 2004 (35% to 59%, respectively). However, the survival rates were exceptionally low from 1980 to 1984, and they still remained significantly lower ( 30% to 35%) in the latter time period compared with younger populations. Recent prospective data in advanced-stage HL confirmed this. Outcomes for patients with HL age 60 years on the phase III study E2496 (treated with ABVD [doxorubicin, bleomycin, vinblastine, and dacarbazine] or Stanford V) seemed improved with historical controls but remained much lower compared with patients younger than age 60 years (5-year failure-free survival [FFS] and OS: 48% and 58%, respectively, v 74% and 90%, respectively). Notably, these survival disparities cannot be explained merely by the advanced age of patients. In a recent retrospective analysis of older patients with HL treated in the current era, we reported 5-year progression-free survival (PFS) and OS of 44% and 58%, respectively, which were significantly inferior compared with an ageand sex-matched population (Fig 1). The cause of poor outcomes for older patients with HL is likely multifactorial, including presence of comorbidities and decreased organ reserve leading to increased toxicity and poor tolerability of therapy, which compromises chemotherapy dose-intensity and contributes to treatment-related mortality (TRM). BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) in the “baseline” form has been shown to be too toxic with a reported TRM rate of 21% in patients with HL age 66 to 75 years. Many bleomycin-containing regimens, including ABVD, are poorly tolerated; this is partly from the risk of the potentially lethal adverse event, bleomycin lung toxicity (BLT). The incidence of BLT in the literature is variable, including up to 46%. Older age is a well-described risk factor associated with BLT in addition to cumulative bleomycin dose, renal insufficiency, pulmonary radiation, and high fractions of inspired oxygen. The incidence of BLT in our Chicago series of patients with HL age 60 years was 32% with an associated mortality rate of 25%. Furthermore, the rate of BLT was much higher in patients who received granulocytestimulating growth factor versus those who did not (ie, 38% v 0%, respectively; P .001), which supports prior data suggesting granulocyte-stimulating growth factor increases the risk of BLT. Several sources of evidence have also suggested that HL in older 0 HL population General US population Ov er al l S ur vi va l ( % )