In an interview conducted during the 7th World Congress on Controversies in Multiple Myeloma (COMy), 2021, Niels van de Donk, MD, PhD, Professor of Cancer Immunology, VU University Medical Center, Amsterdam, Netherlands, discusses the treatment of multiple myeloma resistant to BCMA-targeted therapy. Prof van de Donk describes the challenges of BCMA downregulation in multiple myeloma and other possible targets. Based on poor response to CAR T-cell therapy in patients with biallelic loss of BCMA, Prof van de Donk suggests the use of treatments that target different antigens such as talquetamab and cevostamab, the use of combination treatments, and the use of CAR T cells that can simultaneously target different antigens.