Novel CD19/BCMA Dual-Targeted CAR-T Cell Therapy for the Treatment of Relapsed/Refractory Multiple Myeloma

Prior treatment

• Received bendamustine-containing regimens within 6 months prior to treatment.
• Active infection within 72 hours prior to treatment initiation; subjects on ongoing prophylactic antibiotics, antifungals, or antivirals are not excluded provided there is no evidence of active infection and the antibiotics are not on the prohibited drug list.
• Current systemic use of cyclosporine or steroids such as dexamethasone; recent or current use of inhaled steroids is not exclusionary.

Other illness

• Other serious conditions that may preclude participation in this trial (e.g., central nervous system disorders, severe heart failure, myocardial infarction within the past 6 months, unstable arrhythmia or unstable angina, gastric ulcer, active autoimmune disease, etc.).

Lab values

• Received systemic therapy such as cyclophosphamide and fludarabine for lymphoma clearance within 2 weeks prior to enrollment or single-cell collection; prior CD19/BCMA CAR-T therapy; or cell or bispecific antibody therapy within 8 weeks prior to treatment.
• Hepatitis C virus (HCV) or Human Immunodeficiency Virus (HIV) positive status; any uncontrolled active infection, including active tuberculosis or Hepatitis B virus (HBV) DNA levels ≥1×10³ copies/mL.
• Renal impairment with serum creatinine \>1.5 times the upper limit of normal (ULN).
• Hepatic impairment with AST and/or ALT \>2.5 times ULN and direct bilirubin \>1.5 times ULN.
• Hyponatremia, serum sodium \< 125 mmol/L.
• Baseline serum potassium \< 3.5 mmol/L (exclusion not applied if potassium supplementation prior to study enrollment restores levels above this threshold).

Other

• Pregnant or lactating women.

• Relapsed/refractory multiple myeloma.
• Confirmed by immunohistochemistry (IHC) or flow cytometry of bone marrow samples: plasma cell membrane expression of BCMA is positive (≥30%); no requirement for CD19 positivity rate. All sites must centrally submit bone marrow or plasmacytoma biopsy specimens to the lead site's pathology department or bone marrow/liquid specimens to KingMed Diagnostics (third-party laboratory) for BCMA expression verification.
• Relapsed/refractory patients must meet the following criteria:
  • No response or disease progression after 3 cycles of bortezomib (proteasome inhibitor) or lenalidomide therapy No response or disease progression after 3 cycles of prior treatment regimen Interval between last treatment and disease progression \>30 days No current indication for hematopoietic stem cell transplantation (HSCT), or patient refusal of HSCT
  • Definition of disease progression follows the 2021 International Myeloma Working Group (IMWG) criteria, meeting at least one of the following:
  • Serum M protein ≥ 5 g/L Urine M protein ≥ 200 mg/24 h If serum free light chain (FLC) ratio is abnormal, patient FLC level ≥ 100 mg/L Biopsy-confirmed evaluable plasmacytoma Increased myeloplasmacytic percentage ≥25% (absolute increase ≥10%) Myeloplasm cells constitute ≥30% of total bone marrow cells
• Expected survival \>12 weeks;
• Disease status is evaluable and meets at least one of the following:
  • Serum M-protein ≥10 g/L, 24-hour urine M-protein ≥ 200 mg, Serum FLC ≥ 50 mg/L, Plasmacytoma evaluable by imaging or laboratory testing, Bone marrow plasma cell percentage ≥ 30%
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1;
• Sufficient venous access for apheresis or venipuncture, with no other contraindications to blood cell separation;
• white blood cell (WBC) ≥ 1.5 × 10⁹/L; platelet (PLT) ≥ 45 × 10⁹/L.
• Serum creatinine ≤ 1.5 times the upper limit of normal (ULN).
• Alanine Aminotransferase (ALT) ≤ 2.5 ULN, Aspartate Aminotransferase (AST) ≤ 2.5 ULN.
  • All laboratory values within the above ranges must be achieved without ongoing supportive therapy.