Efficacy and Safety of BCMA Nanobody CAR-T Cell Therapy in Relapsed or Refractory Plasma Cell Myeloma Open Access

• Dual nanobody VHHs (dVHHs) targeting BCMA, achieved a high ORR in the treatment of relapsed or refractory plasma cell myeloma patients.

• Its efficacy extended to extramedullary lesions, high-risk cytogenetic abnormalities, plasma cell leukemia, and anaplastic plasmacytoma.

BCMA CAR-T has demonstrated promising therapeutic efficacy in refractory and relapsed multiple myeloma. However, distinct CAR-T constructs exhibit varying therapeutic outcomes. As the antigen recognition domain, nanobodies offer a small, stable, single-domain structure with enhanced affinity and specificity compared to conventional scFv fragments. We explored the use of nanobody-based BCMA(S103) CAR-T cell therapy for R/R plasma cell myeloma (NCT04447573). The CAR construct incorporates dual nanobody VHHs targeting BCMA (dVHHs). A cohort of 27 patients was treated with S103 CAR-T therapy, which included four cases of plasma cell leukemia, One case of anaplastic plasma cell myeloma. 11 cases had multiple extramedullary lesions. 11 patients exhibited high-risk genetic abnormalities, including 4 with TP53 mutations. One month after CAR-T infusion, the overall response rate (ORR) was 96.3% (26/27), with a CR)+ VGPR rate of 59.2% (16/27). At the three-month follow-up, the ORR increased to 100% (27/27), with a CR+VGPR rate of 81.5% (22/27). The median duration of remission was 11 months ( 2-36 months). The one-year OS rate was 61.1%, and PFS was 57.2%. Conclusion: BCMA CAR-T therapy, utilizing dual nanobody VHHs targeting BCMA, demonstrates a high overall response rate (ORR) and manageable safety profile in treating patients with R/R plasmacytic myeloma, including those with high-risk features such as extramedullary lesions, high-risk cytogenetic abnormalities, plasma cell leukemia, or anaplastic plasmacytoma.