Inclusion Criteria:
1. age 18-75 years old, gender is not limited;
2. Understand and know about this study and sign the informed consent voluntarily;
3. Patients diagnosed with recurrent/refractory plasma cell blood tumors must: a) have
received at least 3 kinds of anti-plasma cell blood tumor therapy, including at least
one proteasome inhibitor and one immunomodulator; b) documented progression within 12
months of treatment of the most recent antiplasmacytic blood tumor, or efficacy
assessed as SD or PD within 60 days of treatment of the most recent antiplasmacytic
blood tumor;
4. meet one of the following detection indicators: a) serum M protein ≥5g/L; b) Urine M
protein ≥200mg/24h; c) Affected serum free light chain ≥100mg/L and abnormal serum
free light chain ratio; d) Bone marrow plasma cell ratio ≥10%;
5. ECOG score is 0-2 points; 6, liver and kidney function, cardiopulmonary function meet
the following requirements: a) blood creatinine ≤150umol/L, or creatinine clearance
(estimated by Cockcroft Gaultra formula) ≥40ml/min (if the kidney function injury
caused by rapid progression of the primary disease, the inclusion criteria can be
appropriately relaxed, and the decision is made by the investigator); b) Total
bilirubin ≤2×ULN; ALT≤3 x ULN, AST≤3 x ULN; c) Echocardiography showed normal
diastolic function, left ventricular ejection fraction (LVEF) ≥50%, and no serious
arrhythmias; d) The subjects had no active pulmonary infection, and the blood oxygen
saturation of indoor air was > 90%;
7. The subjects had no contraindications for peripheral blood monopexy, hemoglobin ≥60g/L,
platelets ≥50×10^9/L, neutrophils ≥1×10^9/L; 8. Expected survival >12 weeks; 9. The urine
pregnancy test of female subjects of childbearing age should be negative and not in the
lactation period; Women or men of reproductive age were required to use effective
contraception throughout the study.
Exclusion Criteria:
1. Have had severe rapid hypersensitivity to any of the drugs to be used in this study;
2. History of central nervous system (CNS) diseases, such as seizures, paralysis,
aphasia, stroke, severe brain injury, dementia, Parkinson's disease, neuropathy; Known
active central nervous system (CNS) involvement or history of modification or clinical
signs of multiple myeloma meningeal/spinal meningeal involvement;
3. Accompanied by other uncontrolled malignancies (except adequately treated cervical
carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer
after radical surgery, ductal carcinoma in situ after radical surgery, and thyroid
cancer after radical surgery);
4. The presence of clinically significant cardiovascular disease, such as uncontrolled or
symptomatic arrhythmias, congestive heart failure, or any grade III (moderate) or
grade IV (severe) heart disease (according to the New York Heart Society Functional
Grading Method NYHA*); Patients with a history of myocardial infarction, angioplasty
or stenting, unstable angina pectoris, or other clinically significant heart disease
within 12 months prior to enrollment;
5. Previous patients with craniocerebral trauma, cerebrovascular accident, more serious
cerebral ischemia or cerebral hemorrhage diseases;
6. The investigator determines that there are serious complications or diseases that
increase the risk of the subject or affect the study, including but not limited to,
for example, cirrhosis of the liver, recent major trauma, etc.;
7. Allogeneic hematopoietic stem cell transplantation performed within six months prior
to screening, or hematopoietic stem cell transplantation performed during the
screening period for any immunosuppressive treatment due to graft-versus-host disease;
8. Patients with autoimmune diseases, immune deficiencies or other immunosuppressants
(other than low-dose glucocorticoids) are required;
9. Any uncontrolled active infection, including but not limited to active tuberculosis;
Suspected uncontrollable fungal, bacterial, viral, or other infection prior to
enrollment;
10. Received attenuated live vaccine within 4 weeks before anapheresis;
11. Subjects with active hepatitis (hepatitis B virus DNA >100IU/ml or hepatitis C virus
RNA [HCVRNA] positive), syphilis, and other acquired and congenital immunodeficiency
diseases, including but not limited to HIV-infected persons; People infected with CMV
virus (CMV DNA test positive);
12. The subject has a history of alcoholism, drug abuse or mental illness;
13. Failure to follow the following treatment requirements needs to be excluded:
A) Hormones: Subjects shall not receive more than 5mg of prednisone or other
equivalent doses of corticosteroids and other immunosuppressive drugs within 72 hours
prior to PBMC cell collection; B) Prior anti-tumor therapy (prior to PBMC monotherapy)
: targeted therapy, epigenetic therapy or investigational drug therapy, or use of
invasive investigational medical devices must have ended 14 days prior to PBMC cell
collection or at least 5 half-lives (whichever is longer); Treatment of multiple
myeloma with monoclonal antibodies ended at least 21 days before cell collection;
Cytotoxic therapy should be completed at least 14 days before cell collection.
Protease inhibitor treatment should end at least 14 days before cell collection. The
immunomodulator should end at least 7 days before cell collection; C) Radiotherapy:
must be completed no later than 4 weeks before PBMC cell collection, but if the
radiotherapy field covered ≤ 5% of bone marrow reserve, participants were eligible to
participate regardless of the radiotherapy end date; D) Anti-T cell antibody drugs
(such as alenzumab) must be terminated 8 weeks before cell collection;
14. Researchers consider it inappropriate to participate in this experiment.
