Lost cell-surface expression of the specific antigen targeted by CAR-T cells is a common finding in resistant tumors but varying across the types of tumors where these therapies are used. In CAR-resistant lymphomas, genomic alterations that impact CD19 are less common than other genomic alterations, but associated resistance mechanisms remain unclear. In multiple myeloma, loss of the CAR-target BCMA from the cell surface commonly occurs without alteration of its encoding gene. The subject of this session is functional laboratory systems than can be employed to evaluate CAR-T resistance, including non-CD19 single-gene alterations in lymphoma and the discovery of targetable BCMA cleavage in myeloma.