Safety and Efficacy of Anti-BCMA/GPRC5D CAR-T Cell Therapy in Treating Relapsed and Refractory Multiple Myeloma(rr/MM)

Inclusion Criteria:

1. Age and gender: 18 years old <= age <= 70 years old, gender unlimited, signinginformed consent voluntarily;
2. According to the classification definition of IMWG standard, the diagnosis ofplasmacytoma is multiple myeloma, plasmacytic leukemia, poems syndrome, monoclonalIMMUNOGLOBULINEMIA, primary macroglobulinemia or primary amyloidosis which are invalidor relapsed after at least three-line treatment (including chemotherapy based onbortezomib and / or lenalidomide);
3. BCMA and GPRC5D were positive on the surface of plasma membrane;
4. The patients could not receive the treatment of HSCT, or the relapse after HSCT wasjudged to need treatment by researchers;
5. ECOG score is 0 or 1;
6. Expected survival time >= 12 weeks;
7. The subjects must have proper organ function and meet all the following laboratorytest results before entering the group
8. Blood routine test: neutrophil >= 1.0 x 10^9 / L; hemoglobin >= 70 g / L;platelet >= 50 x 10^9 / L;
9. Liver function: ALT and AST <= 2.5 x ULN; total bilirubin <= 1.5 x ULN;
10. Renal function: serum creatinine <= 2.5 x ULN; or creatinine clearance calculatedaccording to Cockcroft Gault formula Rate CrCl >= 60 ml / min.
11. Electrolyte: blood potassium >= 3.0 mmol / L; blood calcium >= 2.0 mmol / L;blood magnesium >= 0.5 mmol / L;
12. Coagulation function: fibrinogen >= 1.0g/l; activated partial thromboplastin time (APTT) <= Keywords ULN + 10s; prothrombin time (PT) < ULN + 3S;
13. The subjects should be willing to provide effective diagnosis evidence or bone marrowexamination before treatment, and bone marrow or effective examination aftertreatment;
14. Women of childbearing age and fertile male subjects must take one of the followingeffective contraceptive measures from signing informed consent until one year afteranti-BCMA/GPRC5D CAR-T cell transfusion: abstinence, double barrier contraceptivemethod, IUD, hormone contraceptive;
15. Male subjects were forbidden to donate sperm from signing the informed consent untilone year after anti-BCMA/GPRC5D CAR-T cell transfusion;
16. Sign informed consent
17. The subject must have informed consent to the test before the test, and bevoluntary by himself (or his legal representative) signed the written informedconsent;
18. The subjects or their legal representatives can communicate well with theresearchers and follow the protocol to complete the test.

Exclusion Criteria:

1. Previous treatment history
2. Received hematopoietic stem cell transplantation within 2 months before the startof administration, or within the screening period after transplantation,immunosuppressive therapy was used because of graft-versus-host disease;
3. Patients who had received chemotherapy, immunotherapy, radiotherapy and majorsurgery within 4 weeks before the start of administration;
4. Those who received the live vaccine within 4 weeks before the start ofadministration and / or planned to receive the live vaccine after the trial;
5. Those who have received clinical trial drug treatment or are participating inother clinical trials within 4 weeks before drug administration;
6. History of disease and operation
7. Patients with central nervous system invasion by plasmacytoma;
8. Hypertension and drug treatment can not get good control (blood pressure > 140 / 90 mmHg);
9. Doppler ultrasound evaluation: left ventricular ejection fraction (LVEF) < 50%;
10. Arrhythmia with NCI CTCAE 5.0 grade >= 2, or male QTc > 450 ms, female QTc > 470MS (QTc was calculated by the friderica correction formula QTc = QT / rr0.33);patients with a history of tip torsion or congenital QT prolongation syndrome;
11. Patients with any of the following diseases within 12 months beforeadministration: myocardial infarction, severe or unstable heart, patients withcolic, coronary artery bypass or peripheral artery bypass grafting, congestiveheart failure, cerebrovascular events (including transient ischemic attack), etc;
12. During the screening period, the researchers judged that there wereuncontrollable and active infectious diseases;
13. People infected with human immunodeficiency virus (HIV);
14. HBsAg was positive and in the active phase of hepatitis B (HBV DNA quantity >= 1.00 x 10^2 copies / ml);
15. Hepatitis C antibody (anti HCV) was positive and was in the active phase ofhepatitis C (hepatitis C RNA was not in the normal mode)Perimetric value);
16. The researchers judged patients with severe electrolyte disorder;
17. Patients with a clear tendency of gastrointestinal bleeding, including thefollowing: local active ulcer focus, and stool occult blood (>= + +); patientswith a history of black stool and hematemesis within 2 months; researchersbelieve that digestion may occur Patients with massive bleeding of the Tao;
18. Patients with a history of solid organ transplantation;
19. The investigator or sponsor thinks that he / she has other acute, serious orchronic medical or psychological diseases and is not suitable for participationAdd clinical trial;
20. Pregnant and nursing women
21. Prohibited treatment and / or medication
22. At the same time, other anti-tumor drugs, including traditional Chinese medicine,were used;
23. At the same time, take drugs that can prolong QT interval (including class IA andIII antiarrhythmic drugs);
24. Those who need to receive oxygen every day;
25. Long term use of corticosteroids (except for local inhalation);
26. others
27. Those who have a history of psychoactive drug abuse and are unable to give up orhave mental disorders;
28. Habitually drink grapefruit juice or excessive tea, coffee and / or caffeinatedbeverages during the trial Unable to give up;
29. According to the judgment of the researchers, there are serious concomitantdiseases endangering the safety of patients or affecting the completion of thetrialillnes.