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Ivan Borrello, MD, associate professor of oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, talks about the potential of adoptive T-cell therapies in the treatment of multiple myeloma.

Offering an overview of how chimeric antigen receptor (CAR) T-cell therapy works — from gene modification to antibody expression to protein targets — Borrello discusses distinct approaches currently under investigation.

“The rationale for targeting myeloma with a CD19 is … has significant biological appeal … and potentially some clinical validity as well.”

He details the dramatic reduction in disease burden and disappearance of gene-modified T cells seen in research at the University of Pennsylvania and why the findings offer “a dominant explanation” for CAR T-cell therapy efficacy.

Borrello highlights another method being studied at the NCI targeting B-cell maturation antigen (BCMA).

“The NIH has shown … there appears to be rather significant responses associated with these BCMA-targeted CAR T cells in patients that have received the highest dose.”

He delves into the associated cytokine release syndrome that has “confounded” the field and describes algorithms and “suicide genes” in development that stand to improve tolerability.

Additionally, he highlights the potential issue of antigen-escape variants upon relapse and related investigations underway at Johns Hopkins involving marrow infiltrating lymphocytes.

Borello notes CD38 and kappa and lambda light chains as other areas being explored but that the efficacy data is still premature.

“Immunotherapy is quickly becoming a mainstay in the treatment of multiple myeloma,” he said. “Adoptive T-cell therapy, as well as checkpoint inhibitors and ultimately vaccines, will all be playing a role.”