Comparison of Outcomes By Age of Patients with Limited Stage Hodgkin Lymphoma Treated with ABVD Alone; A Secondary Analysis of the Canadian Cancer Trial Group HD.6 Trial

Introduction: Management options for individuals with early-stage Hodgkin lymphoma (HL) include combined modality therapy (CMT), and chemotherapy alone. The HD.6 randomized phase III trial, in which ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) alone was compared with radiation based therapy, comprises the largest prospectively collected data set of individuals with limited stage HL treated with ABVD alone with long-term follow-up [Meyer JCO 2005, NEJM 2012]. Adolescents and young adults (AYAs) with cancer are considered a vulnerable population, in part due to unique psychosocial challenges and distinct disease biology. The most common cancer observed among AYAs is HL. However, studies focusing specifically on AYAs diagnosed with limited stage HL are scarce. We sought to evaluate the impact of age on outcomes of individuals with stage IA and IIA non-bulky HL, treated with ABVD alone. Methods: Individuals randomly assigned to ABVD chemotherapy alone on the HD.6 clinical trial formed the study population for this secondary analysis. The Kaplan-Meier life-table method was used to calculate the rates of overall survival (OS), event free survival (EFS) and freedom from disease progression (FFDP) defined as in the original trial. The primary analysis used univariate and multivariate Cox regression models with age included as a continuous variable. The following covariates were used in the multivariate analysis: age, gender, ECOG performance status (0-1 vs. ≥ 2), stage, erythrocyte sedimentation rate (ESR, 30 years old were compared with the use of the log-rank test for time to event endpoints and Chi-squared test for response rates, acute toxicity and chemotherapy administration. All analyses were based on the locked data base of July 15, 2011. Results: Of 196 eligible patients assigned to ABVD alone, median age was 34 years (range 17 to 68), 106 (54%) were male and 76 (38.8%) were 60 years at study enrolment and > 65 years at death. There was no statistical difference in overall response rates (62/76, 81.6% vs. 97/120 80.8%), acute grade 3 and 4 toxicities, or chemotherapy administration between those aged under 30, or over 30 years. Conclusions : In this randomized phase III trial of individuals with limited stage Hodgkin lymphoma, clinical outcomes of AYAs were comparable with those of adults in middle age. However, deaths were most prominent in older patients > 60 years at the time of diagnosis and predominantly from causes other than Hodgkin lymphoma, explaining the impact of age as a continuous variable on survival but not disease progression. Disclosures Winter: Merck: Research Funding; Glaxo-Smith-Kline: Research Funding. Hay: Celgene: Research Funding; Roche: Research Funding; Abbvie: Research Funding; Kite: Research Funding; Amgen: Research Funding; Janssen: Research Funding; Novartis: Research Funding.