Rituximab and eculizumab when treating nonmalignant hematologic disorders: infection risk, immunization recommendations, and antimicrobial prophylaxis needs

Rituximab and eculizumab, monoclonal antibodies that deplete most B cells and activate the terminal complement, respectively, are used to treat nonmalignant hematologic disorders (NMHDs), sometimes with unfavorable effects on the immune system. Hypogammaglobulinemia and neutropenia have been reported with variable prevalence in patients treated with rituximab. Neutropenia is mild and transient, and serious infectious complications are uncommon, so treatment is not indicated. Hypogammaglobulinemia is of greater concern. There is a lack of agreement on a standardized definition, and pre- and posttreatment immunoglobulin (Ig) levels are not routinely obtained. The association among low Ig levels, infectious risk, and mortality and morbidity in this population is unclear. There are also no formal guidelines on indication, risk factors, and threshold level of IgG to prompt Ig replacement therapy (IgRT). Among patients with NMHD, preexisting or persistent hypogammaglobulinemia (PH) after treatment with rituximab has been linked to underlying primary immunodeficiency disorders; therefore, a high index of suspicion should be maintained, and immunologic and genetic evaluation should be considered. Overall, important strategies in managing patients who are receiving rituximab include routine monitoring of pre- and posttreatment IgG levels, immune reconstitution (eg, B-cell subsets), assessment of vaccination status and optimization before treatment, and individualized consideration for IgRT. Accordingly, we discuss immunizations. Eculizumab, most commonly used in the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome, poses increased risk of meningococcal infections. To decrease the risk of infection, a meningococcal vaccination series is recommended before initiating therapy, and prophylactic antibiotics are preferred during the course of treatment.