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Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Shaji K. Kumar, MD
Prashant Kapoor, MD, FACP
Posted: Friday, September 23, 2022
Mirco Friedrich, MD, PhD, of Heidelberg University Hospital, Germany, and colleagues aimed to elucidate the lack of knowledge surrounding predictors of response, molecular mechanisms, and resistance mediators of adaptive immunotherapy by T-cell engagers in multiple myeloma. Presented during the 2022 International Myeloma Society (IMS) Annual Meeting and Exposition (Abstract OAB-002), the results of this study may provide a new framework for understanding T-cell–activating immunotherapy and how it may improve antitumor immunity.
“This is the first study to provide a deep interrogation of the human T-cell repertoire and its dynamics in response to T-cell engagers, and our data set provides a valuable resource of real-time T-cell fates and their modulation by multiple myeloma and immunotherapy,” stated the study authors. “We provide the rationale for predictive immune monitoring and conditioning of the immune repertoire to guide future immunotherapy approaches in multiple myeloma.”
Primary multiple myeloma samples were obtained from patients who were newly diagnosed and those with relapsed or refractory disease who underwent experimental treatment with a BCMA x CD3 bispecific antibody. Bone marrow–associated immune cells were collected from healthy donors.
To compare the immune repertoire pretreatment at two timepoints, longitudinal site-matched bone marrow biopsies were performed. These data were integrated with individual and global repertoire-level analyses by tracing T-cell clones over time using the amino acid sequence of each T-cell receptor.
The investigators discovered conserved behaviors of bone marrow residing CD8-positive and CD4-positive T cells among patients with multiple myeloma receiving therapy with T-cell engagers. They demonstrated that the immune landscape of bone marrow not only seems to react to T-cell–targeting immunotherapy with clonal expansion of T cells and phenotype diversification, but also to malignant disease progression.
Additionally, the study authors identified a subset of CD8-positive T cells that continuously progressed to a dysfunctional state from an early effector. Of note, this process is mediated by clonal replacement of circulating T cells in peripheral blood, whereas clinical response failure is regulated by the high abundance of dysfunctional CD8-positive T cells.
Disclosure: Disclosure information was not provided.
2022 IMS Annual Meeting and Exposition
