Table 5.

CAR T-cell therapy in MM: open questions.

Issue
CAR T-cell therapy failure	Reasons for failure: Malignancy; Immune-associated; Patient-factors; Antigen escape. Strategies to overcome antigenic loss: Sequential or combined infusion with CAR T-cells against targets other than BCMA; CAR T-cells with novel dual-targeting vector design; BCMA expression upregulation; New potential targets of immunotherapy: CD138, GPRC5D, transmembrane activator, calcium-modulator, cyclophilin ligand, signaling lymphocytic activation, and molecule); NKG2D ligands, CD229 and integrin β; Moving CAR T-cell therapy into the earlier treatment lines.
Safety	CRS: tended to be grade 1 or 2; NT has not been a significant issue in MM CAR T-cell trials, Cytopenias; Hypogammaglobulinemias; The possibility that CAR T therapies are managed on an outpatient basis or with a reduction in the days of hospitalization.
Extended timeline of the manufacturing process	Solutions: Novel bioengineering methods; Lymphocytes from allogeneic donors; Use of induced pluripotent stem cell (iPSC)-derived immune cells; CAR NK cells against.
Access to therapy	Accredited centers are required; ICU and Neurology services; Support social; High cost.
Patient selection	Patients with a lower disease burden to prevent early relapse.