Abstract
Background: Survival outcomes for older patients with diffuse large B-cell lymphoma (DLBCL) are disproportionally inferior to those of younger patients. While differences in tumor biology may play a role, older patients are often frail with comorbidities, polypharmacy, and use potentially inappropriate medications (PIM) such as anticholinergics and benzodiazepines.
Methods: Using Cox proportional hazard and logistic regression models, we analyzed all DLBCL patients age ≥60 treated at our two affiliated hospitals from 2009-2014 to examine the association of polypharmacy and PIM use with progression-free survival (PFS), overall survival (OS), and treatment-related toxicities.
Results: In this updated and final analysis, we included 132 patients with complete records from these two hospitals. They share similar demographic, clinical, and laboratory characteristics except for higher International Prognostic Index (IPI) in patients from one hospital. The median age was 70 years (range 65-76). At the time of diagnosis, 47% of patients used more than 4 medications (polypharmacy) and 48% used at least one PIM. Only 42% of patients received first-line chemotherapy of adequate relative dose intensity (>85% dosage), and 66% experienced ≥grade 3 toxicities. PIM use and polypharmacy were associated with shortened PFS and OS by log-rank test. Most importantly, PIM use remained an independent predictor of PFS, OS, and ≥grade 3 toxicities in multivariable analysis (Table 1).
Conclusion: This is the first report of significantly adverse survival impacts of PIM use in elderly patients with DLBCL, presumably from drug-drug interactions that increase toxicities and impair the delivery of adequate chemotherapy dosage. Our findings support the use of evidence-based geriatric principles to guide meticulous medication management to improve outcome disparity for these patients.
Diefenbach: Genentech: Consultancy, Honoraria, Research Funding.
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