Severe Infections After Rituximab-Based Therapy for B-Cell Lymphoproliferative Disorders: A Five-Year Retrospective Cohort Study from Western Romania

Background and Objectives: We evaluated the incidence, spectrum, and baseline factors associated with severe infection after rituximab-based therapy for B-cell lymphoproliferative disorders in Western Romania. Materials and Methods: This retrospective cohort included 142 adults starting rituximab-containing therapy between January 2020 and December 2024. The primary outcome was infection according to the Common Terminology Criteria for Adverse Events grade ≥ 3 within 12 months. Analyses included competing-risk cumulative incidence estimation, exploratory multivariable logistic regression, restricted cubic splines, bootstrap validation, and decision-curve analysis. Results: Severe infection occurred in 38 patients (26.8%; 95% confidence interval [CI] 20.2–34.6); the 12-month cumulative incidence accounting for death as a competing event was 27.1%. Lower respiratory tract infections predominated (39.5%), and 42.1% of severe events occurred within 90 days. Hypogammaglobulinaemia at 6 months affected 39.1% of evaluable patients. In an exploratory multivariable model (36 events; nine predictors), associations were observed for baseline immunoglobulin G < 6 g/L (adjusted odds ratio [aOR] 4.96; 95% CI 1.28–19.18), serum albumin < 35 g/L (aOR 4.67; 95% CI 1.78–12.23), diabetes mellitus (aOR 2.73; 95% CI 1.03–7.24), and age per decade (aOR 1.83; 95% CI 1.11–2.99), whereas continuous immunoglobulin G showed a weaker association (aOR per 1 g/L 0.93; 95% CI 0.78–1.11). The optimism-corrected C-statistic was 0.717 (apparent, 0.789), and the corrected calibration slope was 0.671, indicating overfitting. Conclusions: Severe infections were frequent following rituximab-based therapy. Baseline immunoglobulin levels, albumin, diabetes, and age were associated with severe infection and, if confirmed, may help identify patients for closer surveillance. The exploratory prediction model showed reduced performance after internal validation and requires external validation before clinical implementation.