Anti-CD20 monoclonal antibodies(BASF Corp.)

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.

Background/Objectives: Radiotherapy (RT) is a mainstay of clinical cancer therapy that causes broad immune responses. The complement system is a pivotal effector mechanism in the innate immune response, but the impact of RT is less well understood. This study investigates the interaction between RT and the complement system as a possible approach to improve immune responses in cancer treatment. Methods: Human solid cancer (lung, prostate, liver, breast cancer), lymphoma, and leukemia cells were irradiated using X-rays and treated with polyclonal antibodies or anti-CD20 monoclonal antibodies, respectively. Chromium release assay was applied to measure cell lysis after radiation with or without complement-activating antibody treatment. The expression of membrane-bound complement regulatory proteins (mCRPs; CD46, CD55, CD59), which confer resistance against complement activation, CD20 expression, apoptosis, and radiation-induced DNA double-strand breaks (γH2AX), was measured by flow cytometry. The radiosensitivity of tumor cells was assessed by colony-forming assay. Results: We demonstrate that RT profoundly impacts complement function by upregulating the expression of membrane-bound complement regulatory proteins (mCRPs) on tumor cells in a dose- and time-dependent manner. Impaired complement-mediated tumor cell lysis could thus potentially contribute to radiotherapeutic resistance. We also observed RT-induced upregulation of CD20 expression on lymphoma and leukemic cells. Notably, complement activation prior to RT proved more effective in inducing RT-dependent early apoptosis compared to post-irradiation treatment. While complement modulation does not significantly alter RT-induced DNA-damage repair mechanisms or intrinsic radiosensitivity in cancer cells, our results suggest that combining RT with complement-based anti-cancer therapy may enhance complement-dependent cytotoxicity (CDC) and apoptosis in tumor cells. Conclusions: This study sheds light on the complex interplay between RT and the complement system, offering insights into potential novel combinatorial therapeutic strategies and a potential sequential structure for certain tumor types.