2025 Update of Cellular Immunotherapy for Plasma Cell Disorders

Despite PFS in MM patients extending to 17 years due to contemporary quadruplet induction therapies, there remains a necessity for novel products in the treatment of highrisk patients. BCMA, GPRC5D, FcRH5, SLAMF7, and TACI represent the principal CAR-T target molecules, with dual-targeted treatments under development to enhance their efficacy. Ide-cel and Cilta-cel are CAR-T cells directed against BCMA, having received FDA approval for RRMM 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 against conventional treatments. The development of academic CAR-Ts 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. The real-world data have demonstrated comparable efficacy and safety outcomes in both academic and commercial CAR-T research. CAR-T cell researchs are also being undertaken in SMM and AL amyloidosis. CAR-PRISMM and CAR-HiRiSMM are regarded as extremely effective and safe for patients with high-risk SMM. NXC-201, which targets BCMA, has been developed for AL amyloidosis. Notwithstanding these promising outcomes, numerous difficulties confront CAR-T therapy. These factors may relate to the tumor, the patient, and the CAR-T product. To overcome these issues, strategies are being implemented, including combination therapy, the incorporation of gamma-secretase inhibitors etc. In conclusion, CAR-T treatments have evolved into an effective therapy modality being anticipated to be utilized in earlier phases in the future. Gene editing (CRISPR) method contributes to the future perspective.

Keywords: Myeloma and other plasma cell dyscrasias, Neoplasia, Antigen recognition by T lymphocytes, Immunology, Molecular hematology