Incidence of infections in patients treated with rituximab for autoimmune disorders of hematological Interest or non-Hodgkin lymphoma

Rituximab is employed in the treatment of B-cell non-Hodgkin lymphomas (NHL) and autoimmune disorders of hematological interest (ADHI), such as autoimmune hemolytic anemia (AIHA), acquired hemophilia A (AHA), and immune thrombocytopenia (ITP). Rituximab induces profound B-cell depletion, reducing the titer of immunoglobulins and autoreactive antibodies, but secondary hypogammaglobulinemia increases risk of infections. We performed a retrospective, multicentric study across seven Italian centers to compare two cohorts of patients with either indolent NHL or ADHI treated with rituximab between March 2014 and March 2024. We evaluated the incidence and characteristics of infections and common antimicrobial prophylaxis adopted according to local clinical practice, in the absence of shared guidelines for ADHI. We included 285 patients (52% female; median age 55 years). The ADHI cohort comprised 187 patients (65%; 97 ITP, 78 AIHA, 12 AHA), while the control group included 98 i-NHL patients (34%). We documented 65 infectious events occurring in 65/285 patients (22.8%). Infection-related mortality occurred in 9 patients (4%). When stratified, the cumulative 180-day incidence of infections was 9.4% (IC95% 8.8%-10%) for NHL patients and 13.7% for ADHI (IC95% 12.2%-14.2%). Multivariate analysis identified prophylaxis (OR 2.62, p = 0.014) and post-treatment hypogammaglobulinemia (OR 2.73 p = 0.004) as risk factors. The risk of infection in patients with ADHI is high and comparable to that observed in NHL. Therefore, close monitoring of IgG levels is strongly advised, and mortality can be contained through rigorous antimicrobial stewardship.