1:Hospital Clínic de Barcelona; 2:IDIBAPS

Despite recent therapeutic advances, the prognosis of multiple myeloma (MM) patients when refractory to several drugs remains poor. Thus, new strategies using immunotherapy to improve outcomes are imperative. Chimeric antigen receptor (CAR) T-cell therapy is changing the treatment landscape of this disease, providing a very effective option for patients who are refractory to standard treatment. B-cell maturation antigen (BCMA)-targeted CAR T-cells have established outstanding results in heavily pre-treated patients. However, several other antigens are currently under investigation with promising results. Two products, Ide-cel and Cilta-cel have been approved for clinical use. ARI0002h, our academic humanized CAR-T against BCMA, has shown very encouraging results both about efficacy and safety, with all 30 patients showing response, deeper clearance of bone marrow and extramedullary disease, as well as no neurotoxicity and low grade cytokine release syndrome. Unfortunately, relapses after CAR T-cell infusion are still reported. Hence, understanding the underlying mechanisms of resistance is essential to promote prevention strategies and to enhance CAR T-cell efficacy in this multiple myeloma.