Infection Risk, Mortality, and Hypogammaglobulinemia Prevalence and Associated Factors in Adults Treated with Rituximab: A Tertiary Care Center Experience

Abstract

Background: Rituximab is a human monoclonal antibody directed against the B-cell transmembrane protein CD20. Although well-tolerated, given its mechanism of action, rituximab can induce a state of severe immunosuppression, increasing the risk of opportunistic and fulminant infection and mortality. Aim: To evaluate the risk of infection, mortality, and hypogammaglobulinemia and their associated factors among rituximab receivers. Method: This was a single-center retrospective cohort study of adults treated with rituximab for various indications. Hypogammaglobulinemia was defined by a cut-off value below the normal limit (an IgG level of <7.51 g/L, an IgM level of <0.46 g/L, and/or an IgA level of <0.82 g/L). Patients who met the definition of hypogammaglobinemia solely based on IgA were excluded. Severe infection was defined as any infection that required intensive care unit admission. Results: A total of 137 adults with a mean age of 47.69 ± 18.86 years and an average BMI of 28.57 ± 6.55 kg/m2 were included. Hematological malignancies and connective tissue diseases were the most common primary diagnoses for which rituximab was used. More than half of the patients received the 375 mg/m2 dose. Rituximab’s mean cumulative dose was 3216 ± 2282 mg, and the overall mortality rate was 22.6%. Hypogammaglobulinemia was diagnosed in 43.8% of the patients, and it was significantly more prevalent among males and the 375 mg/m2 and 500 mg doses. Hematological malignancy was the only predictor for infection. Patients with blood type AB or B, hematological malignancies, and corticosteroids had a significantly higher mortality rate. Receiving the 1000 mg dose and having a low CD19 were associated with a significantly lower risk of infection and mortality, respectively. Conclusions: Hypogammaglobulinemia was diagnosed in 43.8% of the patients, and it was significantly more common among males and the 375 mg/m2 and 500 mg doses. Hematological malignancies were significantly associated with higher infection and mortality rates, while corticosteroids were significantly associated with a higher mortality. Since the culprit of mortality was infection, these findings highlight the critical need for more frequent immunological monitoring during rituximab treatment period to mitigate the burden of infection and identify candidates for immunoglobulin replacement.