A Study of VRd-based Regimen Combined With CART-ASCT-CART2 Treatment in NDMM Patients With P53 Abnormalities

Inclusion Criteria:

1. Willing and able to give written informed consent (ICF) .
2. Age ≥ 18 years and ≤ 65 years.
3. Meet the internationally accepted Criteria for the diagnosis of newly diagnosedmultiple myeloma (Chinese guidelines for the diagnosis and management of multiplemyeloma (revised in 2022) criteria)
4. Patients have not received previous anti-multiple myeloma-related chemotherapy, havenot received previous extensive pelvic radiotherapy (more than half of the pelvicarea), and have not received previous anti-multiple myeloma hormone therapy, exceptfor those who have used hormones for no more than 14 days for symptom control.
5. The patient have one or more measurable multiple myeloma lesion, must include one ofthe following conditions:

• Serum M protein≥1.0 g/dL(10g/L)
• Urine M protein≥200 mg/24h
• Serum free light chain(sFLC): κ/λ FLC ratio is abnormal and affected FLC ≥10mg /dL

6. p53 gene abnormalities: Plasma cells were enriched by CD138 immunomagnetic and thendetected by FISH. Cut-off ≥20%., or P53 mutation by second-generation sequencing.
7. ECOG scores 0 - 1;
8. No active infection
9. All screening blood biochemistry: tests should be performed according to the protocoland within 14 days before enrollment. Screening laboratory values must meet thefollowing criteria： a.TBIL<1.5 x upper limit of normal (ULN) (<3 x ULN in patientswith Gilbert's syndrome); b.AST and ALT <3 x ULN.; c. Creatinine clearance ≥ 60mL/min (calculated using Cockroft-Gault formula).
10. normal pulmonary function and oxygen saturation ≥ 92% on room air.
11. Routine blood tests (performed within 7 days, no RBC transfusion, noG-CSF/GM-CSF/platelet agonists, no drug correction within 14 days before screening, noPLT transfusion within 7 days) : WBC ≥ 1.5 x 109/L, ANC ≥ 1.0 x 109/L, Hb ≥ 85 g/L PLY ≥ 75 x 109/L (if BMPC < 50%) or PLT ≥ 50 x 109/L (if BMPC ≥ 50%)
12. Patients must be able to take prophylactic anticoagulant therapy as recommended by thestudy.
13. The woman is not breastfeeding, is not pregnant and agrees not to be pregnant duringthe study period and for the following 12 months. Male patients agreed that theirspouse would not become pregnant during the study period and for 12 months thereafter.
14. Willing and able to complete the study procedures and follow-up examinations.

Exclusion Criteria:

1. Plasma cell leukemia.
2. Documented active amyloidosis.
3. Multiple myeloma with central nervous system (CNS) invasion
4. Unsuitable for autologous stem cell transplantation, such as severe cardiopulmonarydisorders
5. Patients with peripheral neuropathy greater than grade 2 or peripheral neuropathygreater than grade 2 with pain at baseline, regardless of whether they were currentlyreceiving medical therapy
6. Known intolerance, hypersensitivity, or contraindication to BCMA-CART cellularproducts.
7. Patients with unstable or active cardiovascular system disease, meeting any of thefollowing:
8. Unstable angina pectoris, symptomatic myocardial ischaemia, myocardial infarctionor coronary artery reconstruction within 180 days prior to the first dose.
9. Uncontrolled hypertension (>140/90 mmHg with blood pressure fluctuations of morethan 180/100 mmHg over a 6-month period).
10. Uncontrolled and clinically significant conduction abnormalities (e.g. patientswith ventricular arrhythmias controlled by antiarrhythmic medication), notexcluding patients with 1st degree atrioventricular (AV) block or asymptomaticleft anterior bundle branch block/right bundle branch block (LAFB/RBBB)).
11. Congestive heart failure (CHF) classification ≥ grade 3 as defined by the NewYork Heart Association (NYHA).
12. Left ventricular ejection fraction (LVEF) <50% on echocardiography.
13. History of stroke or intracranial haemorrhage within 12 months prior toscreening.
14. Presence of a serious thrombotic event prior to treatment.
15. Known positive serology for HIV or HIV seropositivity.
16. Active hepatitis B or C infection. Screening requires serologic testing for hepatitis.If hepatitis B surface antigen and hepatitis B core antibody were positive, a negativeDNA polymerase chain reaction (PCR) result was needed before enrollment (afteranti-hepatitis B therapy, a negative DNA polymerase PCR result was confirmed beforeenrollment). If the hepatitis C antibody was positive, the RNA PCR test should benegative prior to enrollment
17. Life expectancy of <3 months
18. Women who are pregnant or breastfeeding
19. Any active gastrointestinal dysfunction that affects the patient's ability to swallowtablets, or any active gastrointestinal dysfunction that may affect the absorption ofthe studied treatment medication
20. Subjects had major surgery within 2 weeks before randomization (for example, generalanesthesia), or is not fully recovered from the surgery, or surgery is arranged duringstudy period.
21. Received live attenuated vaccine within 4 weeks prior to study treatment.
22. According to the researcher's judgement, any condition including but not limited toserious mental illness, medical illness or other symptoms/conditions that may affectstudy treatment, compliance, or the capability of providing informed consent.
23. Necessary medication or supportive therapy is contraindicated with study treatment.
24. Any diseases or complications that may interfere with the study.
25. Patients are not willing to or cannot comply with study scheme.