2025 Update of Cellular Immunotherapy for Plasma Cell Disorders

Despite progression-free survival in multiple myeloma (MM) patients extending to 17 years due to contemporary quadruplet induction therapies, there remains a necessity for novel products in the treatment of high-risk patients. BCMA, GPRC5D, FcRH5, SLAMF7, and TACI are the principal chimeric antigen receptor T (CAR-T) cell target molecules, with dual-target treatments under development to enhance treatment efficacy. Ide-cel and cilta-cel are CAR-T cells directed against BCMA, having received approval from the U.S. Food and Drug Administration for relapsed/refractory MM based on the phase 2 KarMMa and CARTITUDE trials, respectively. Research is currently being conducted on the administration of these products in newly diagnosed patients and for maintenance therapy. Additional anti-BCMA targeted medicines, including LCAR-B38M, completely humanized CAR-T (FHVH-T), P-BCMA-ALLO-1, ALLO-715, and anti-BCMA CAR-NK, provide promising treatment options. Moreover, the anti-CD19 Fast-CAR, designed to shorten production time, and PHE885, which possesses in vivo proliferation capability, are regarded as very efficacious. Arlo-cel, developed for the significant target GPRC5D, has demonstrated efficacy compared to conventional treatments. The development of academic CAR-T products such as ARI0002h, HBI0101, eque-cel, zevor-cel, anito-cel, and Sleeping Beauty (utilizing a non-viral vector) have importance due to their accessibility and cost-effectiveness. Real-world data have demonstrated comparable efficacy and safety outcomes in both academic and commercial CAR-T research. CAR-T cell studies are also being undertaken for smoldering MM and amyloid light-chain (AL) amyloidosis. CAR-PRISMM and CAR-HiRiSMM are regarded as extremely effective and safe therapies for patients with high-risk smoldering MM. NXC-201, which targets BCMA, has been developed for AL amyloidosis. Notwithstanding these promising outcomes, numerous difficulties still confront CAR-T therapy. These factors may be related to the tumor, the patient, and/or the CAR-T product. To overcome these issues, new strategies are being implemented, including combination therapy and the incorporation of gamma-secretase inhibitors. In conclusion, CAR-T treatments have evolved into an effective therapy modality and are anticipated to be utilized in earlier treatment phases in the future. The CRISPR gene editing method contributes to future perspectives.