Monitoring of the Complement System Status in Patients With B-Cell Malignancies Treated With Rituximab
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Rituximab is a pioneering anti-CD20 monoclonal antibody that became the first-line drug used in
immunotherapy of B-cell malignancies over the last twenty years. Rituximab activates the
complement system in vitro, but there is an ongoing debate on the exact role of this
effector
mechanism in therapeutic effect. Results of both in vitro and in vivo studies are
model-dependent and preclude clear clinical conclusions. Additional confounding factors like
complement inhibition by tumor cells, loss of target antigen and complement depletion due to
excessively applied immunotherapeutics, intrapersonal variability in the concentration of main
complement components and differences in tumor burden all suggest that a personalized approach
is the best strategy for optimization of rituximab dosage and therapeutic schedule. Herein we
critically review the existing knowledge in support of such concept and present original data on
markers of complement activation, complement consumption, and rituximab accumulation in plasma
of patients with chronic lymphocytic leukemia (CLL) and non-Hodgkin's lymphomas (NHL). The
increase of markers such as C4d and terminal complement complex (TCC) suggest the strongest
complement activation after the first administration of rituximab, but not indicative of
clinical outcome in patients receiving rituximab in combination with chemotherapy. Both ELISA
and complement-dependent cytotoxicity (CDC) functional assay showed that a substantial number of
patients accumulate rituximab to the extent that consecutive infusions do not improve the
cytotoxic capacity of their sera. Our data suggest that individual assessment of CDC activity
and rituximab concentration in plasma may support clinicians' decisions on further drug
infusions, or instead prescribing a therapy with anti-CD20 antibodies like obinutuzumab that
more efficiently activate effector mechanisms other than complement.
Reference
Felberg, A., Taszner, M., Urban, A., Majeranowski, A., Jaskuła, K., Jurkiewicz, A., ... & Okrój, M. (2020). Monitoring of the complement system status in patients with B-cell malignancies treated with rituximab. Frontiers in immunology, 11, 2956.
For Research Use Only.
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