CART therapy has showed good safety and efficacy in treatment of lymphoma and acute lymphoblastic leukemia. Researchers want to see if this helps people with high risk multiple myeloma after auto-HSCT.To test the safety and efficacy of giving targeting CD19 and BCMA T cells in treating high risk multiple myeloma followed with auto-HSCT.

Adults ages 18-75 with high risk Multiple Myelomas (R-ISS III stage or with extramedullary infiltration or with del(17p), t(4;14), t(14;16), t(14;20), 1q21+ or disease progression during treatment).

Design:

Participants may be screened with:

Medical history Physical exam Blood and urine tests Heart tests Bone marrow sample Multiple scans and X-rays Participants will have apheresis. Blood is removed through a needle in an arm. T cells are removed. The rest of the blood is returned through a needle in the other arm.

The cells will be changed in a laboratory. Participants will get auto-HSCT. Hematopoietic reconstitution after auto-HSCT, participants will get the T cells through the IV within 3 days. Maintenance therapy with IMiDs was received after combined CAR T infusion.

After this, participants will stay in the hospital for at least 9 days and stay nearby for 2 weeks. Then they will have blood tests and see a doctor.

Participants will visit the clinic 1, 2, 3, 6, 9 and 12 months after the infusion, then every 3-6 months until disease progression. A bone marrow sample will be taken at the 3-6 months visit.

Inclusion Criteria:

• Multiple myeloma patients eligible for auto-HSCT.
• High risk multiple myeloma (R-ISS III stage or with extramedullary infiltration or with del(17p), t(4;14), t(14;16), t(14;20), 1q21+ or disease progression during treatment).
• Expected survival ≥ 3 months.
• Creatinine < 2.0 mg/dl.
• Blood coagulation function: PT and APTT <2x normal.
• Arterial blood oxygen saturation>92%.
• ALT(alanine aminotransferase)/AST (aspartate aminotransferase)< 3x normal
• Karnofsky scores ≥ 60 and ECOG score≤2.
• Adequate venous access for apheresis, and no other contraindications for leukapheresis.
• Patients should not take immunotherapy in three months prior to CART cells infusion.
• Voluntary informed consent is given.

Exclusion Criteria:

• Pregnant or lactating women.
• Uncontrolled active infection.
• Active hepatitis B or hepatitis C infection.
• Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
• Previously treatment with any gene therapy products.
• Any uncontrolled active medical disorder that would preclude participation as outlined.
• HIV infection.
• History of myocardial infarction and severe arrhythmia in half a year.
• Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
• Patients with fever of unknown origin (T>38℃).