A study presented at the 2020 ASH Annual Meeting found that tafasitamab in combination with rituximab mediates increased tumor cell death in vitro in patients with diffuse large B-cell lymphoma (DLBCL), supporting “the clinical evaluation of this antibody combination in patients with DLBCL,” according to the authors.
Researchers assessed the effect of this treatment combination on antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and tumor B-cell viability in vitro.
Researchers analyzed a panel of 11 aggressive lymphoma cell lines, including nine with DLBCL and two with Burkitt’s lymphoma. For the ADCC assays, tumor cells were incubated with tafasitamab and/or rituximab at saturating concentrations in the presence of natural killer cells from healthy human donors at effector-to-target (E:T) ratios of 0.5:1 to 3:1 for two hours. For the ADCP assays, lymphoma cells were incubated with tafasitamab and/or rituximab at saturating concentrations in the presence of in vitro differentiated macrophages derived from healthy human donors at an E:T ratio of 2:1 for three hours. Phagocytosis was assessed by quantification of double-positive events.
Researchers observed increased ADCC activity for the combination of tafasitamab and rituximab compared with the respective monotherapies in four of the 11 cell lines. For the remaining cell lines, the combination activity was similar to the most active monotherapy (tafasitamab, 5; rituximab, 2).
In five of 11 cell lines, the combination of tafasitamab and rituximab resulted in enhanced ADCP activity compared with the monotherapies. The combination activity in the other cell lines was comparable to the most active monotherapy (tafasitamab, 2; rituximab, 4).
Treatment of tumor cells with the respective antibodies without effector cells showed a beneficial combination effect of tafasitamab with rituximab on the reduction of cell viability in three of eight cell lines, whereas two cell lines were primarily sensitive to tafasitamab and three were sensitive to rituximab. This observed difference in the activity profile of tafasitamab versus rituximab suggests different mechanisms for induction of direct cytotoxicity, according to the authors.
Researchers also assessed expression levels of c-Myc and observed a correlation between decreased cell viability and reduction of c-Myc expression. This finding is in line with the role of c-Myc in the regulation of cellular processes, such as proliferation and apoptosis.
“The co-treatment of tafasitamab with rituximab demonstrated superiority compared with the respective monotherapies for at least one and up to all three of the modes of action tested (ADCC, ADCP, or direct impact on cell viability) in [nine of] 11 lymphoma cell lines,” the researchers concluded.
Reference
Patra M, Augsberger C, Ginzel C, et al. The Combination of Tafasitamab and Rituximab Increases Cytotoxicity Against Lymphoma Cells In Vitro. Abstract 2095. Presented at the 62nd American Society of Hematology Annual Meeting & Exposition, December 2-11, 2020.
