B Cell Maturation Antigen（BMCA）-Targeted CAR-T for Refractory/Relapsed Multiple Myeloma

Inclusion Criteria:

* 1\. Age≥18，male or female;
* 2\. ECOG 0-3;
* 3\. Clearly diagnosed as multiple myeloma (MM) \[according to IMWG 2014 criteria\];
* 4\. Patients should have received 3 different regimens prior to enrollment (each regimen should last for at least one complete cycle, except for the case of disease progression);
* 5\. Previously received one PI and IMiD treatment;
* 6\. MM patients should fit one of the following: 1) disease progression; 2) relapsed after CR. The corresponding criteria is defined as follows: a, disease progression should satisfy at least 1 of the following: serum M protein ≥0.5g/dl, or urine M protein\>200mg/24h, or FLC increasement \>10mg/dl, or bone marrow plasma cell proportion \>10%, or with new bone disease/plasmacytoma/original focus increased by 50% or more, or hypercalcemia ( corrected serum calcium level \>11.5mg/dL(2.65mmol/L); b. relapse after CR, should satisfy one of the following: ①M protein in urine or blood; ②bone marrow plasma cell proportion≥5%; ③manifestation of disease progression, such as plasmacytoma, osteolytic lesions or hypercalcemia.
* 7\. Peripheral blood mononucleated cell separation should be at least 2 weeks from chemo/radiotherapy;
* 8\. Neutrophil count≥1000/ul, platelet count≥45000/ul, Hb\>60g/l;
* 9\. Cardiac, hepatic and renal function: Creatinin \<1.5 times of normal maximum；ALT/AST level \<2.5 times of the maximum of normal range; total bilirubin\<1.5 times of ULN；cardiac ejection fraction≥ 50%; no pericardial effusion within 6 weeks prior to enrollment;
* 10\. Being able to understand and willing to sign the written consent;
* 11\. Fertile patients should agree to take contraceptive measures during the process of this trial.

Exclusion Criteria:

* 1\. History of other tumors other than multiple myeloma, except for the following: malignant tumor after radical surgery, and have been inactive for ≥3 years prior to enrollment; skin cancer (not melanoma) after sufficient treatment, no evidence of disease at enrollment;
* 2\. History of the following treatment: received targeted therapy, epigenetic therapy or clinical trials, invasive operation within 14 days/5 half-time prior to enrollment. History of monoclonal antibody within 21 days prior to enrollment. History of cytotoxic medicine or proteasome treatment within 14 days prior to enrollment. History of immunomodulatory treatment within 7 days prior to enrollment;
* 3\. History of \>5mg/d systemic prednisone treatment (or other glucocorticoids of the equivalent dosage) within 2 weeks prior to peripheral mononucleated cell collection;
* 4\. With CNS involvement or clinical manifestation of meningeal myeloma;
* 5\. With active systemic infection;
* 6\. With active HBV infection or HCV infection, or history of type C hepatitis;
* 7\. With immunodeficiency, including HIV infection;
* 8\. With the following heart condition: NYHA level III or IV congestive heart failure; myocardial infarction or CABG within 6 months prior to enrollment; clinically meaningful ventricular arrythmia, or history of idiopathic syncope (not caused by vascular-vagal disorder or dehydration), history of non-ischemic myopathy;
* 9\. With active autoimmune disease;
* 10\. History of autologous stem cell transplantation within 6 weeks prior to enrollment;
* 11\. History of allogenic stem cell transplantation.