Anti-CD20 monoclonal antibodies(BASF Corp.)

Complement-dependent cytotoxicity (CDC) is one of the main mechanisms of action for approved therapeutic anti-CD20 immunoglobulin (Ig) G antibodies, including rituximab, ofatumumab, and ocrelizumab, in the treatment of B-cell lymphoma patients. However, resistance to these therapies inevitably develops in patients, and thus novel antibody approaches are needed. Here, we described the CDC activity of an anti-CD20 IgM in comparison to an anti-CD20 IgG. We applied live-cell imaging and kinetic analysis to measure CDC activity in real time. Through this imaging platform, we demonstrated that an IgM antibody exhibited more potent and faster target cell killing through CDC compared with an IgG antibody. Additionally, an IgM antibody was more effective at killing target cells with low antigen density, in low levels of complement, and in the presence of high complement inhibitor expression. An anti-CD20 IgM also showed superior CDC against ex vivo tumor samples from a patient with B-cell lymphoma. These preclinical studies demonstrated the potential of an anti-CD20 IgM-based therapeutic antibody having superior CDC in B-cell lymphoma compared with a traditional IgG antibody.

Anti-CD20 monoclonal antibodies (mAbs) are highly effective in managing multiple sclerosis (MS), but may also increase infection risk and reduce vaccine responses. Alternative dosing strategies (ADS), such as extended-interval dosing (EID) and dose reduction, have been proposed to optimize safety and personalize treatment. This systematic review and meta-analysis was conducted to compare standard dosing strategies (SDS) to ADS of anti-CD20 mAbs in MS patients.

A systematic search of Pubmed, Web of Science and Scopus was conducted and included clinical studies that reported relapse rates, MRI activity, disability progression, or NEDA-3 status. Two reviewers independently extracted study and patient data. Risk ratios (RRs) were pooled using random-effects models RESULTS: A systematic search identified 2237 studies, of which 19 met inclusion criteria. Included studies spanned from 2018 to 2024 and investigated ocrelizumab (n = 13), rituximab (n = 5), and ofatumumab (n = 1). Most studies (n = 16) examined EID, while three evaluated dose reduction. Compared to the standard group, EID showed no significant difference in relapse rates (RR = 0.67; 95 % CI: 0.43-1.06), MRI activity (RR = 0.87; 95 % CI: 0.57-1.34), disability progression (RR = 0.96; 95 % CI: 0.50-1.85), or NEDA-3 status (RR = 1.12; 95 % CI: 0.78-1.63). Three dose-reduction studies also reported stable clinical and radiological outcomes.

ADS for anti-CD20 mAbs appear comparable to SDS. More specifically, EID does not increase the risk of relapse, MRI activity, disability progression, or NEDA loss. While dose reduction also shows promising results, further evidence is needed for firm conclusions.