The phase I clinical study of CART targeting BCMA with humanized alpaca-derived single-domain antibody as antigen recognition domain.

2535 Background: Several phase I clinical trials already shown Chimeric antigen receptor T cells (CART) targeting BCMA has the promised effects to treat the relapsed/refractory (RR) multiple myeloma (MM), RRMM. We developed CART cells (CART-BCMA) using one single-domain antibody as recognition domain. The anti-BCMA single-domain antibody was derived from the alpaca, and humanized with the affinity of 1.14nM. The CART-BCMA use the 4-1BB and CD3ζ intracellular regions as T cell activation domain. Methods: A phase I, single arm clinical study was conducted to assess safety and efficacy of CART-BCMA. The enrolled RRMM patients had received average 10 lines of prior treatment, no matter BCMA expression level on plasma cells. Patients were subjected to a lymphodepleting regimen with Cy (300-600 mg/m2, d-5, -4) and Flu (30 mg/m2, d-5 to d-3) before CART infusion at the dose of 2-10×106 CAR+ cells/kg. The efficacy was assessed based on the IMWG Criteria, and the toxicity was graded by CTCAE 4.02. Results: As of December 31, 2018, 16 patients were infused with autologous CART-BCMA cells, and had at least 1 month of follow-up. Many patients have M protein in serum, but haven't the high percent of plasma cells in bone marrow, which are difficult to be treated by CART cells because the tumor cells are aggregated, not diffused in bone marrow. 3 patiens were diagnosed with extramedullary diseases, were evaluated as PR at D28 (tumor SPD decreasing >50%). 13 patients haven't extramedullary diseases, at D28, ORR is 84.6% (11/13); At 10 weeks, 7 patients were evaluated, ORR is 100% (sCR/CR 42.8%, VGPR 14.3% , PR 42.8% ); 5 patients reached 16 weeks, 1 relapsed, 4 kept remission. The Pt3 and Pt6 shows the CRS grade 3 or 4, other patients shows the grade 0-2 CRS, the CRS is manageable. Conclusions: Our result demonstrates the promising efficacy compared with other reported results of CART targeting BCMA, and supports further development of this anti-RRMM cellular immunotherapy. Clinical trial information: NCT03661554.