Infection-related morbidity and mortality among older patients with DLBCL treated with full- or attenuated-dose R-CHOP

Abstract

Infection-related morbidity and mortality are increased in older patients with diffuse large B-cell lymphoma (DLBCL) compared with population-matched controls. Key predictive factors for infection-related hospitalization during treatment with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and deaths as a result of infection in older patients during and after treatment with R-CHOP remain incompletely understood. For this study, 690 consecutively treated patients age 70 years or older who received full-dose or attenuated-dose R-CHOP treatment were analyzed for risk of infection-related hospitalization and infection-related death. Median age was 77 years, and 34.4% were 80 years old or older. Median follow-up was 2.8 years (range, 0.4-8.9 years). Patient and baseline disease characteristics were assessed in addition to intended dose intensity (IDI). Of all patients, 72% were not hospitalized with infection. In 331 patients receiving an IDI ≥80%, 33% were hospitalized with ≥1 infections compared with 23.3% of 355 patients receiving an IDI of <80% (odds ratio, 1.61; 95% confidence interval, 1.15-2.25; P = .006). An increased risk of infection-related admission was independently associated with IDI >80% across the whole cohort. Primary quinolone prophylaxis independently reduced infection-related admission. A total of 51 patients died as a result of infection. The 6-month, 12-month, 2-year, and 5-year cumulative incidences of infection-related death were 3.3%, 5.0%, 7.2%, and 11.1%, respectively. Key independent factors associated with infection-related death were an International Prognostic Index (IPI) score of 3 to 5, Cumulative Illness Rating Scale for Geriatrics (CIRS-G) score ≥6, and low albumin, which enabled us to generate a predictive risk score. We defined a smaller group (15%) of patients (IPI score of 0-2, albumin >36 g/L, CIRS-G score <6) in which no cases of infection-related deaths occurred at 5 years of follow-up. Whether patients at higher risk of infection-related death could be targeted with enhanced antimicrobial prophylaxis remains unknown and will require a randomized trial.