Ripertamab

Rituximab is a chimeric anti-CD20 monoclonal antibody that targets CD20-expressing B lymphocytes, has a well-defined efficacy and safety profile, and is broadly used to treat a wide array of diseases. In this review, we cover the mechanism of action of rituximab and focus on hypogammaglobulinemia and late-onset neutropenia-2 immune effects secondary to rituximab-and subsequent infection. We review risk factors and highlight key considerations for immunologic monitoring and clinical management of rituximab-induced secondary immune deficiencies. In patients treated with rituximab, monitoring for hypogammaglobulinemia and infections may help to identify the subset of patients at high risk for developing poor B cell reconstitution, subsequent infections, and adverse complications. These patients may benefit from early interventions such as vaccination, antibacterial prophylaxis, and immunoglobulin replacement therapy. Systematic evaluation of immunoglobulin levels and peripheral B cell counts by flow cytometry, both at baseline and periodically after therapy, is recommended for monitoring. In addition, in those patients with prolonged hypogammaglobulinemia and increased infections after rituximab use, immunologic evaluation for inborn errors of immunity may be warranted to further risk stratification, increase monitoring, and assist in therapeutic decision-making. As the immunologic effects of rituximab are further elucidated, personalized approaches to minimize the risk of adverse reactions while maximizing benefit will allow for improved care of patients with decreased morbidity and mortality.

When first introduced, rituximab (RTX), a chimeric anti-CD20 monoclonal antibody, brought about an alternative therapeutic paradigm for primary membranous nephropathy (PMN). Rituximab was shown to be effective and safe in PMN patients with kidney dysfunction, with. patients receiving second-line rituximab therapy achieving remission as effectively as those patients who had not previously received immunotherapy. No safety issues were reported. The B cell-driven protocol seems to be as efficient as the 375 mg/m² × 4 regimen or 1 g × 2 regimen in achieving B cell depletion and remission, but patients with high M-type phospholipase A2 receptor (PLA2R) antibody levels may benefit from a higher dose of rituximab. While rituximab added another therapeutic option to the treatment regimen, it does have limitations as 20 to 40% of patients do not respond. Not all patients respond to RTX therapy for lymphoproliferative disorders either, therefore further novel anti-CD20 monoclonal antibodies have been developed and these may provide alternative therapeutic options for PMN. Ofatumumab, a fully human monoclonal antibody, specifically recognizes an epitope encompassing both the small and large extracellular loops of the CD20 molecule, resulting in increased complement-dependent cytotoxic activity. Ocrelizumab binds an alternative but overlapping epitope region to rituximab and displays enhanced antibody-dependent cellular cytotoxic (ADCC) activities. Obinutuzumab is designed to have a modified elbow-hinge amino acid sequence, leading to increased direct cell death induction and ADCC activities. In PMN clinical studies, ocrelizumab and obinutuzumab showed promising results, while ofatumumab displayed mixed results. However, there is a lack of randomized controlled trials with large samples, especially direct head-to-head comparisons. Alternative molecular mechanisms have been suggested in this context to explore novel therapeutic strategies. B cell activator-targeted, plasma cell-targeted and complement-directed treatments may lead to novel therapy paradigms for PMN. Exploratory strategies for the use of drugs with different mechanisms, such as a combination of rituximab and cyclophosphamide and a steroid, a combination of rituximab and a calcineurin inhibitor, may provide more rapid and efficient remission, but the combination of standard immunosuppression with rituximab could increase infection risk.