In vitro comparison of CD20xCD3 biosimilar antibodies against diffuse large B-cell lymphoma (DLBCL) cell lines with different levels of expression of CD20.

Although CD20xCD3 bispecific antibodies (BsAbs) have demonstrated transformational activity in diffuse large B-cell lymphoma (DLBCL), some patients fail to respond and others relapse. To begin to explore possible limitations, we compared the in vitro activity of four CD20xCD3 biosimilar BsAbs against four DLBCL cell lines with CD20 expression ranging over a 100-fold. All four biosimilar BsAbs demonstrated superior in vitro activity to rituximab, with biosimilar glofitamab consistently being the most potent. Moreover, biosimilar glofitamab and odronextamab retained significant activity in the presence of low-level CD20 expression. Finally, one DLBCL cell line exhibited intrinsic resistance to all four CD20xCD3 BsAbs despite inducing marked T-cell and NK-cell activation.