Anti-BCMA CAR T-Cell Therapy in Relapsed or Refractory Multiple Myeloma with Extramedullary Disease and Plasma Cell Leukemia

Abstract

Background: Extramedullary myeloma (EMM) and primary plasma cell leukemia (pPCL) remains a treatment challenge even in the era of new drugs. The prognosis of EMM is inferior, and the median overall survival of patients who experience an extramedullary relapse is < 6 months. Chimeric antigen receptor (CAR)- B-cell maturation antigen (BCMA) has the potential for the treatment of EMM and PCL. Methods: Between February 22, 2017 and June 25, 2018, twenty-eight R/R MM patients (including fourteen EMM patients) and 2 pPCL patients received median dose of 11.2 × 106 CAR+ cells/kg (range, 5.4 – 25.0 × 106 CAR+ cells/kg). Patients had a median of 4 (range, 3 – 11) prior lines of therapy, including a proteasome inhibitor and/or an immunomodulatory agent. A lymphodepleting chemotherapy with cyclophosphamide 20mg/kg and fludarabine 25 mg/m2 daily on days -4 to -2 was administered before infusion of CAR-BCMA T cells on day 0. Findings: Hematologic toxic effects were the most common events of grade 3 or higher, including neutropenia (in 96.7% of the patients), lymphopenia (in 100%), anemia (in 76.7%), and thrombocytopenia (in 80.0%). Grade 3 or higher cytokine release syndrome and neurologic events occurred in 16.7% and 3.3% of the patients, respectively. The objective response rate (ORR) was 90%, and the complete response (CR) rate was 43.3%. One of 2 primary Plasma cell leukemia achieved CR, and another achieved a very good partial response (VGPR). With a median follow-up of 385 days, relapse occurred in nine of the 13 patients who had a CR. The median progression-free survival (PFS) and overall survivals (OS) were 158 days and 427 days. The median OS of patients with EMM/PCL was 243 days. Interpretation: CAR-BCMA T cell treatment is safe and effective in heavily treated R/R Multiple Myeloma with Extramedullary disease. Trial Registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn. Number, ChiCTR OPC16009113). Funding Statement: This work is supported by the funding from the Key Program of the National Natural Science Foundation of China (81830008 and 81630006, to Dr. J.Z.), the Clinical research program of Huazhong University of Science and Technology affiliated Tongji Hospital (2019YBKY016, to Dr. J.Z.), the National Natural Science Foundation of China (81873452, to Dr. C.L.;81670152, to Dr. L.H.; 81600120, to Dr. N.W.). Declaration of Interests: The authors declare no competing financial interests. Ethics Approval Statement: This study was conducted in compliance with the Declaration of Helsinki. The study protocol was approved by the institutional review board of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology.