Single agent rituximab in patients with follicular or mantle cell lymphoma: clinical and biological factors that are predictive of response and event-free survival as well as the effect of rituximab on the immune system: a study of the Swiss Group for Clinical Cancer Research (SAKK)

Abstract

We defined the characteristics predicting response and EFS to rituximab. Prolonged treatment results in longer EFS at the cost of a longer reduction in B cell and IgM levels, but without additional clinical toxicity.

Metastatic colorectal cancer cells from patients previously treated with chemotherapy are sensitive to T-cell killing mediated by CEA/CD3-bispecific T-cell-engaging BiTE antibody

“…Bargou et al (2008) showed the safety of a BiTE antibody, blinatumomab (a BiTE with dual specificity for CD19 and CD3), in their clinical trial, and confirmed that responses to blinatumomab as a single agent occurred in B-cell lymphoma patients at a serum level of 0.6 ng ml À1 . This is about five orders of magnitude below serum levels reported for the monoclonal antibody rituximab at standard doses, which similarly elicits objective responses as a single agent in this disease (Hainsworth et al, 2003;Ghielmini et al, 2005). The enormous potency difference between the BiTE blinatumomab and a conventional antibody could be explained by a greater number of T cells attacking an individual tumour cell (both due to more T cells that are able to recognise tumour and Figures 2 and 3).…”

Lenalidomide down-regulates the CD20 antigen and antagonizes direct and antibody-dependent cellular cytotoxicity of rituximab on primary chronic lymphocytic leukemia cells

“…4 The importance of ADCC in rituximab efficacy is supported by 4 non-Hodgkin lymphoma (NHL) trials in which patients bearing the Fc␥RIIA-H131R and Fc␥RIIIA-V158F highaffinity Fc␥R polymorphisms exhibited improved response to rituximab therapy. [5][6][7][8][9] Whereas in vitro studies demonstrate rituximab can mediate ADCC against primary CLL cells, 2,10 one preliminary study did not identify correlation of response with high-affinity Fc␥R polymorphisms. 11 This has prompted investigation of innate immune enhancing agents to improve both ADCC and rituximab efficacy.…”

Ocaratuzumab, an Fc-engineered antibody demonstrates enhanced antibody-dependent cell-mediated cytotoxicity in chronic lymphocytic leukemia

“…Ocaratuzumab induced similar ADCC to obinutuzumab at all E:T ratios tested (all P > 0. 20). These data have effectively demonstrated that in CLL cells Fc-engineered ocaratuzumab mediates superior allogeneic ADCC when compared with the non-Fc-engineered ofatumumab or rituximab at both lower antibody concentrations and smaller E:T ratios.…”