Safety and Efficacy of Anti-GPRC5D CAR-T Cells Therapy in the Treatment of r/r MM

Inclusion Criteria:

1. The patient understands and voluntarily signs the informed consent, and is expected tocomplete the follow-up examination and treatment of the study procedure.
2. Age 18 to 75 years old, gender is not limited.
3. Diagnosed with multiple myeloma according to IMWG diagnostic criteria.
4. Have received third-line or above treatment.
5. Have measurable lesions at screening period, defined as any of the following : (1)serum monoclonal immunoglobulin (M-protein) level ≥1.0 g/dL. (2) urine M protein level ≥200 mg/ 24h. (3) Light chain multiple myeloma diagnosed with no measurable lesion inserum or urine: serum immunoglobulin free light chain is ≥10 mg/dL and serumimmunoglobulin κ/γ free light chain ratio is abnormal.
6. The patient has recovered from the toxicity of the previous treatment, that is, theCTCAE toxicity grade is less than 2 (unless the abnormality is related to the tumor oris in a stable state as judged by the investigator, which has little effect on safetyor efficacy).
7. Eastern cooperative oncology group (ECOG) score is 0-2, and survival is expected to begreater than 3 months.
8. Has proper organ function: (1) Alanine aminotransferase (ALT) ≤3 times the upper limitof normal (ULN). (2) Aspartate aminotransferase (AST) ≤3 times ULN. (3) Totalbilirubin ≤1.5 ULN. (4) Serum creatinine ≤1.5 ULN, or creatinine clearance ≥60 mL/min. (5) Indoor oxygen saturation ≥92%. (6) Left ventricular ejection fraction (LVEF) ≥45%,echocardiography confirmed no pericardial effusion, no ECG findings with clinicalsense. (6) There was no clinically significant pleural effusion.
9. The venous access required for collection can be established, and there are nocontraindications to leukocyte collection.

Exclusion Criteria:

1. Have been diagnosed with or treated for aggressive malignancies other than multiplemyeloma within 3 years.
2. Subjects who have received the following therapies before blood collection: havereceived targeted therapy, epigenetic therapy, or investigational drug therapy orinvasive investigational medical device within 14 days or at least five half-lives,whichever is shorter, or have treated with monoclonal antibodies within 21 days, orhave received cytotoxic therapy within 14 days, or have treated with a proteasomeinhibitor within 14 days, or have treated with an immunomodulatory agent within 7days, or have received radiotherapy within 14 days (except bone marrow reserve withfield coverage ≤ 5%).
3. It is suspected that MM has involved the central nervous system or meninges and hasbeen confirmed by MRI or CT, or there are other active central nervous systemdiseases.
4. Patients with macroglobulinemia, POEMS syndrome (polyneuropathy, organ enlargement,endocrine disease, monoclonal proteinosis, and skin changes) or primary AL amyloidosisat the time of screening.
5. Hepatitis B surface antigen (HBsAg) is positive, or Hepatitis B core antibody (HBcAb)positive while HBV DNA titer in peripheral blood higher than the lower limit ofdetection. Hepatitis C virus (HCV) antibody positive and the peripheral blood HCV RNAalso positive. Human immunodeficiency virus (HIV) antibody positive. Cytomegalovirus (CMV) DNA test results ≥500 copies /mL. Syphilis test positive.
6. Those with a history of severe allergies or known any of the active ingredients,excipients or mouse-derived products contained in the drug, or those allergic toxenogeneic proteins in this trial, including lymphocyte depletion regimens. Severeallergy history is defined as an allergic reaction of grade two or above, and any ofthe following clinical manifestations occur when an allergic reaction occurs: airwayobstruction (runny nose, cough, wheezing, dyspnea), hypercardia tachycardia,hypotension, arrhythmia, gastrointestinal symptoms (nausea, vomiting), incontinence,laryngeal edema, bronchospasm, cyanosis, shock, respiration, cardiac arrest.
7. Severe heart disease, including but not limited to severe arrhythmia, unstable angina,massive myocardial infarction, New York Heart Association class III or IV cardiacinsufficiency, refractory hypertension (refractory Hypertension is defined as: on thebasis of improving lifestyle, a reasonable tolerable and sufficient amount of ≥3 kindsof antihypertensive drugs (including diuretics) has been used for > 1 month and theblood pressure has not reached the standard, or the blood pressure can only beachieved effective control after taking ≥4 kinds of antihypertensive drugs.
8. Systemic diseases judged by investigators to be unstable, including but not limited tosevere liver, kidney or metabolic diseases requiring drug treatment.
9. Patients with acute/chronic graft-versus-host disease (GVHD) within 6 months prior toscreening, or requiring immunosuppressive therapy for GVHD.
10. Active autoimmune or inflammatory diseases of the nervous system (eg, Guillain-Barresyndrome (GBS), amyotrophic lateral sclerosis (ALS)) and clinically significant activecerebrovascular disease (eg, cerebral edema) , Posterior Reversible EncephalopathySyndrome (PRES)).
11. Those who have tumor emergencies (such as spinal cord compression, intestinalobstruction, leukostasis, tumor lysis syndrome, etc.) before screening or reinfusionand need emergency treatment.
12. The presence of an uncontrolled bacterial, fungal, viral or other infection requiringantibiotic treatment.
13. Those who have undergone major surgical operations (except diagnostic surgery andbiopsy) within 4 weeks before clearing the lymph cells, or those who plan to undergomajor surgery during the study period, or those whose surgical wounds have not healedcompletely before enrollment.
14. Those who have received (attenuated) live virus vaccine within 4 weeks beforescreening.
15. Persons with severe mental illness.
16. Those who are alcoholics or have a history of drug abuse.
17. Pregnant or lactating women, female subjects who plan to have a pregnancy within 2years after cell infusion, and male subjects whose partners plan to have a pregnancywithin 2 years after cell infusion.
18. Patients who are contraindicated with any study procedure or have other medicalconditions that may expose them to unacceptable risks in accordance with theinvestigator's judgment and/or clinical standards. 19. Patients who, in the judgmentof the investigator and/or clinical standards, are contraindicated with any studyprocedure or have other medical conditions that may expose them to unacceptable risks.