Treatment with Full Chemotherapy Regimens in Older Adults with Hodgkin Lymphoma Improves 3-Year Overall Survival, but Less Than Half Receive Full Regimens
Authors: Rodday Angie Mae , Hahn Theresa E. , Kumar Anita J , Lindenauer Peter K , Friedberg Jonathan W. , Evens Andrew Matthew , Parsons Susan K 
Published: November 2019

Introduction
Older adults with Hodgkin Lymphoma (HL) have markedly poorer outcomes than younger counterparts. This may reflect treatment decisions, age-related factors, and/or disease biology. For younger patients, standard first-line treatment typically consists of dose-dense, multi-agent chemotherapy regimens with or without radiotherapy (RT). In contrast, older patients who are deemed unfit for full-dose chemotherapy may receive reduced or partial chemotherapy regimens or RT alone. We describe the association between first-line treatment in older patients with HL and 3-year overall survival (OS).
Methods
We analyzed Surveillance, Epidemiology and End Results (SEER)-Medicare data from 1999-2014. Patients diagnosed with incident classical HL at age ≥65 years and enrolled in Medicare Part A and B fee for service were included. First-line treatment within 4 months of diagnosis was determined from inpatient, outpatient, and physician/supplier claims using chemotherapy J-codes, HCPCS codes, and DRG codes. Treatment was categorized as: 1) full chemotherapy regimen (e.g., ABVD/AVD), 2) partial chemotherapy regimen, 3) single chemotherapy drug or RT, or 4) no treatment. No treatment was defined by lack of claims for any treatment, which may result in misclassification.
Three-year OS from time of diagnosis was estimated for all patients using the Kaplan-Meier method. Analyses comparing 3-year OS by treatment excluded the no treatment group because of immortal time bias (patients need to survive to treatment initiation) and lack of comparability with the treated groups even after adjustment (e.g., residual confounding by poor prognosis). Unadjusted 3-year OS was plotted by treatment category using the Kaplan-Meier method. A Cox proportional hazards model estimated hazard ratios (HR) and 95% confidence intervals (CIs) for the association between first-line treatment and 3-year OS, adjusted for age at diagnosis, race/ethnicity, Medicaid dual enrollment, comorbidity, frailty, diagnosis year, histology, stage, B symptoms, prior cancer, population density, and region. Adjusted HRs are also reported for patient and disease factors associated with 3-year OS.
Results
We included 2825 patients with a mean age of 76 years (SD=7). Patients received the following first-line treatments: 1197 (42.4%) full chemotherapy regimen, 503 (17.8%) partial chemotherapy regimen, 397 (14.1%) single chemotherapy or RT, and 728 (25.8%) no treatment. 92.3% of full chemotherapy regimens were ABVD/AVD. By 3 years post-diagnosis, OS for all patients was 46.7%.
In unadjusted analysis including only treated patients (n=2097), those receiving full chemotherapy regimens experienced the highest 3-year OS, followed by single chemotherapy or RT, then partial chemotherapy regimens (Figure). In the Cox model adjusted for patient and disease factors, treatment with partial chemotherapy regimens (HR 2.12; 95% CI=1.75, 2.58) or single chemotherapy or RT regimens (HR 1.60; 95% CI=1.26, 2.03) were associated with a higher hazard of mortality by 3 years compared to treatment with full chemotherapy regimens.
The adjusted Cox model also identified patient and disease factors associated with 3-year OS. Older patient age (HR 1.03 per year; 95% CI 1.01, 1.04), any comorbidity (HR 1.40; 95% CI 1.09, 1.79), frailty (HR 1.32; 95% CI 1.67), advanced stage (HR 1.45; 95% CI 1.22, 1.74), B symptoms (HR 1.59; 95% CI 1.31, 1.94), and lymphocyte depleted histology (HR 1.75 vs nodular sclerosis; 95% CI 1.17, 2.60) were associated with a higher hazard of mortality by 3 years. Conversely, lymphocyte rich histology (HR 0.57 vs nodular sclerosis; 95% CI 0.32, 1.00) had a lower hazard of mortality.
Conclusions
In a comprehensive analysis, we confirm poor outcomes of older patients with HL, with a 3-year overall mortality &gt;50%. Although &gt;40% of patients received full chemotherapy regimens, 25.8% had no documented treatment. Patients treated with full chemotherapy regimens had the highest 3-year OS compared to other treatment groups. Patients with no documented treatment may reflect a different subgroup of patients with poor prognosis, extensive comorbidity, or death before treatment initiation. Shared-decision making about treatment choices should consider competing risks of death from non-HL causes. Those who are able to tolerate full chemotherapy regimens, sequential therapy, or novel agents may benefit with significantly longer OS.
Figure

Disclosures
Friedberg: Bayer: Honoraria, Other: Data & Safety Monitoring Committee; Acerta: Other: Data & Safety Monitoring Committee. Evens:Pharmacyclics: Honoraria, Other: DMC; Bayer: Consultancy, Honoraria; Research to Practice: Honoraria; Seattle Genetics: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; Affimed: Consultancy, Honoraria; Takeda: Research Funding; Merck: Research Funding.