In patients with multiple myeloma (MM) receiving treatment with bispecific T-cell engagers (TCEs), an international team of researchers has identified conserved behaviors of CD4+ and CD8+ cells and shown that, in non-solid tumors, T-cell state and tumor recognition are prerequisites of clonal T-cell expansion and clinical response.

Predictive indicators of TCE response are needed to guide treatment strategies because, although TCEs achieve high initial clinical response rates in MM, resistance almost invariably occurs, only a subset of patients achieve durable responses, and some patients fail to respond even when TCE target antigens are highly expressed, write Mirco J. Friedrich, of the Broad Institute of MIT and Harvard and Heidelberg University Hospital, and colleagues in a paper published April 10 in Cancer Cell.

“We examined the impact of TCEs on MM patients by performing a longitudinal interrogation of T cells in the peripheral blood and bone marrow of MM patients, coupled with analysis of expanded TCR clonotypes. From these data, we observed that response to TCEs in MM largely results from and is determined by the clonal expansion of a repertoire of pre-existing T cell clones,” they write.

“We present a map of a highly plastic bone marrow immune landscape that is associated with significant potential for T cell expansion and links the unexpectedly high response of adaptive immunotherapy in multi-refractory hematological malignancies to repertoire fitness. By demonstrating the mechanism of TCE treatment in humans as well as specific mechanisms of immune evasion, we provide the rationale for predictive immune monitoring and conditioning of the immune repertoire to guide future immunotherapy approaches.”

• Friedrich MJ, Neri P, Kehl N, et al. The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients [published online ahead of print, 2023 Mar 9]. Cancer Cell. 2023;S1535-6108(23)00036-3. doi:10.1016/j.ccell.2023.02.008

Tags: bispecific t cell engagers, bite, multiple myeloma, BiTEs, researchers, bispecific, MM