Real-world outcomes and prognostic factors in older adults with early-stage classic Hodgkin lymphoma: A study from the spanish relinf-geltamo registry

Abstract INTRODUCTION Older adults (≥60 years) represent up to a quarter of all classic Hodgkin lymphoma (cHL) cases in Western countries and typically have inferior outcomes due to comorbidities, functional decline, histological differences, and reduced treatment tolerance. Historically underrepresented in clinical trials, their management remains challenging. With improved general health and life expectancy, outcomes may have evolved, particularly in early-stage disease. Earlier studies, such as the GHSG HD10/HD11 trials, reported a 5-year progression-free survival (PFS) of 75% in older patients treated with four cycles of ABVD. This study evaluates real-world characteristics, management, and outcomes in older adults with early-stage cHL in a more contemporary clinical context. METHODS A retrospective multicenter study was conducted within the Spanish Lymphoma Registry (RELINF) (GELTAMO group). We included 206 patients aged ≥60 years with early stage cHL. Collected variables included demographics, histologic subtype, Ann Arbor stage, comorbidities (CIRS-G), functional status (ADL, IADL), and geriatric syndromes. Treatment was classified as curative intent (ABVD or other anthracycline-based regimens) or palliative. Response and survival outcomes were assessed. RESULTS Median age was 71.5 years (range 60–91); 53.9% were male. The most frequent histologic subtypes were mixed cellularity (29.6%) and nodular sclerosis (28.6%). EBER was positive in 45.4% of tested cases. Stage I and II disease accounted for 25.2% and 74.8%, respectively, with unfavorable risk features in 60.2%. B symptoms were present in 20.9%, bulky disease in 5.3%, and extranodal involvement in 6.8%. Cardiovascular disease was present in 39.3%, previous malignancies in 24.3%, and geriatric syndromes in 11.7%. Most patients (90.3%) received curative-intent therapy, predominantly ABVD (76.7%). Radiotherapy alone was administered to 2.9%, and 6.8% received palliative treatment. After first-line therapy, 96.1% achieved complete metabolic response, 7.2% had partial response, and one patient progressed. Complementary radiotherapy was used in 51.5%. After a median follow-up of 54.5 months (range 8–108), 59 patients had died: due to HL progression (37.3%), infections (11.9%), treatment toxicity (8.5%), and unrelated causes (42.4%). The 2- and 5-year OS rates were 93.3% and 78.5%. Among patients treated with curative intent, OS was 95% and 81.5% at 2 and 5-year, respectively, versus 73.3% and 37.7% in the palliative group (p=0.001). Two- and 5-year PFS were 85.2% and 71.8% overall. Univariate analysis identified worse OS associated with age >71 years, ischemic heart disease, functional dependence (ADL/IADL), geriatric syndromes, cardiac and psychiatric comorbidities (CIRS-G), stage II, ECOG >0, Barthel index <100, palliative treatment, and history of another malignancy. In multivariate analysis, independent adverse prognostic factors included stage II (HR 7.21, 95% CI 1.41–36.9, p=0.021), palliative treatment (HR 7.94, 95% CI 1.51–41.9, p=0.018), ischemic heart disease (HR 11.3, 95% CI 3.06–42.0, p=0.001), and depression (HR 16.7, 95% CI 3.94–71.0, p=0.001). CONCLUSIONS In this real-world cohort of older adults with early stage cHL, the majority received anthracycline-based treatment with excellent outcomes. A 5-year OS of 81.5% was observed in those treated with curative intent. Stage II disease, ischemic heart disease, and depression emerged as strong independent predictors of poor survival. Notably, almost half of the deaths were unrelated to lymphoma or treatment toxicity, underscoring the relevance of comprehensive geriatric and comorbidity assessment when selecting therapy in this growing patient population.