Durable Remission Achieved from Bcma-Directed CAR-T Therapy Against Relapsed or Refractory Multiple Myeloma

Yarong Liu, Zhi Chen, Hongliang Fang, Runhong Wei, Kang Yu, Songfu Jiang, Weijun Fu, Hua Jiang, Juan Du, Feng He, Ronglin Xie, Jing Chen, Baofeng Wei, Jin Tao and Pin Wang


Background: Promising results are seen from several early phase clinical trials on the cellular immunotherapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) targeting B cell maturation antigen (BCMA) for the treatment of relapsed/refractory (RR) multiple myeloma (MM). We developed an anti-BCMA CAR-T cell product manufactured via gamma-retrovirus-mediated transduction of activated T cells to express a second-generation CAR with the 4-1BB costimulatory domain along with a truncated epidermal growth factor receptor (tEGFR) as a safety switch. The preclinical study confirmed its high reactivity against MM cells.

Methods: We initiated a phase 1 clinical trial (NCT03093168) to evaluate the safety and feasibility of this BCMA CAR-T autologous cellular therapy for treating RRMM. The enrolled RRMM patients either had received at least 3 prior treatment regimens, including a proteasome inhibitor and an immunomodulatory agent, or were double-refractory, and have over 5% BCMA expression on plasma cells (One patient with extramedullary plasmacytoma does not express BCMA). Patients were subjected to a lymphodepleting regimen with Cy (300 mg/m2, d-5 to d-3) and Flu daily for 3 days (25 mg/m2, d-5 to d-3) prior to the CAR-T infusion (d0) at a dose of 9´106 CAR+ cells/kg. The efficacy was assessed by the International Uniform Response Criteria for Multiple Myeloma, and the toxicity was graded by CTCAE 4.03.

Results: As of July 6th, 2018, 17patients had been infused with this intended dose of the autologous BCMA CAR-T cells, and 14 patients had reached at least 1 month of follow-up. As of this data cut-off, the most common non-haematologicalgrade 3 adverse events were pneumonia, hypophosphatemiaand hypocalcemia(two[14%] of 14patients), and fever, cytokine release syndrome,and neurotoxicities (one[7%]of 14patients).All toxicities were fully reversible. The overall response rate (ORR) for the 14 evaluable patients was 79%, including 3 sCRs, 4 CRs and 2 MRD-negative responses (2 VGPR). The CAR-T cell expansion and persistence were consistently observed throughout these patients.The durable remission was observed for two early enrolled patients, with the ongoing objective response (1 sCR and 1 VGPR) lasting more than 15 months.

Conclusions: Our result demonstrates the high potential of this single CAR-T infusion therapy for RRMM, including 3 sCRs and ongoing durable clinical responses, with only mild and manageable CRS to date. These initial data provide strong evidence to support the further development of this anti-myeloma cellular immunotherapy.

Disclosures Liu: HRAIN Biotechnology: Employment. Fang: HRAIN Biotechnology: Employment. He: HRAIN Biotechnology: Employment. Xie: HRAIN Biotechnology: Employment. Chen: HRAIN Biotechnology: Employment. Wei: HRAIN Biotechnology: Employment. Tao: HRAIN Biotechnology: Employment. Wang: Immune Design: Equity Ownership; HRAIN Biotechnology: Consultancy, Equity Ownership.

  • * Asterisk with author names denotes non-ASH members.