A Study of VRD-based Regimen Combined With CART-ASCT-CART2 Treatment in Patients With Primary Plasma Cell Leukemia

Inclusion Criteria:

1. Voluntary written informed consent before performance of any study-related procedurenot part of normal medical care, with the understanding that consent may be withdrawnby the subject at any time without prejudice to future medical care.
2. Age ≥ 18 years and ≤ 65 years.
3. Eastern Cooperative Oncology Group (ECOG) performance status 0, 1, or 2.
4. Life expectancy at least 3 months
5. Definitive diagnosis of pPCL: meet the diagnosis criteria of multiple myeloma (referto the Chinese guidelines for the diagnosis and management of multiple myeloma (revised 2022) criteria) and meeting any of the following:
6. the proportion of tumor plasma cells in peripheral blood leukocytes ≥ 5%;
7. absolute value of peripheral blood tumorigenic plasma cells exceeds 2×10^9/L.
8. Patients have not received previous anti-myeloma related therapy.
9. Measurable disease, as defined by at lease one of the following:
10. Serum monoclonal paraprotein (M-protein) level ≥5g/L.
11. urine M-protein level ≥200 mg/24 hours.
12. If the serum and urine M-protein are unmeasurable, abnormal serum free lightchain (FLC) ratio and affected FLC ≥10 mg/dL.
13. Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathologicalexamination.
14. 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) : ANC ≥ 1.0 x 10^9/L, PLT ≥ 50 x 10^9/L.
15. All screening blood biochemistry: tests should be performed according to the protocoland within 14 days before enrollment. Screening laboratory values must meet thefollowing criteria:
16. Total bilirubin<1.5 x upper limit of normal (ULN);
17. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST);
18. Creatinine clearance ≥ 50mL/min (calculated using Cockroft-Gault formula).
19. Patients must be able to take prophylactic anticoagulant therapy as recommended by thestudy.
20. 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.
21. Willing and able to complete the study procedures and follow-up examinations.

Exclusion Criteria:

1. Secondary plasma cell leukemia.
2. With central nervous system (CNS) involvement.
3. Ineligible for autologous stem cell transplantation, such as severe cardiopulmonarydisorders.
4. Known intolerant, allergic, or resistant to glucocorticoids, bortezomib, lenalidomide,Venetoclax, Selinexor and BCMA-CART cellular products.
5. Patients 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.
6. Patients with unstable or active cardiovascular system disease, meeting any of thefollowing:
7. Unstable angina pectoris, symptomatic myocardial ischaemia, myocardial infarctionor coronary artery reconstruction within 180 days prior to the first dose.
8. Uncontrolled hypertension (>140/90 mmHg with blood pressure fluctuations of morethan 180/100 mmHg over a 6-month period).
9. 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)).
10. Congestive heart failure (CHF) classification ≥ grade 3 as defined by the NewYork Heart Association (NYHA).
11. Left ventricular ejection fraction (LVEF) <50% on echocardiography.
12. History of stroke or intracranial haemorrhage within 12 months prior toscreening.
13. Presence of a serious thrombotic event prior to treatment.
14. Known positive serology for HIV or HIV seropositivity.
15. 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.
16. Ongoing active infection.
17. Prior history of malignancies, unless free of the disease for ≥ 5 years.
18. Pregnant or breast feeding females.
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. According to the researcher's judgment, 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.
21. Necessary medication or supportive therapy is contraindicated with study treatment.
22. Any other medical condition or comorbidity that might interfere with subject'sparticipation.
23. Patients undergoing other experimental therapies.
24. Patients are not willing to or cannot comply with study scheme.