VRd-based Regimen Combined With CART-ASCT-CART2 as First-line Therapy for Newly Diagnosed Multiple Myeloma Patients With P53 Abnormalities：a Prospective, One-arm, Single-center Phase II Study
This is a single-arm, open-label study to evaluate the efficacy and safety of VRD(Bortezomib, Lenalidomide and Dexamethasone)-based regimen combined with CART-ASCT-CART2 in patients with newly diagnosed multiple myeloma with p53 gene abnormalities.
• Willing and able to give written informed consent (ICF) .
• Age ≥ 18 years and ≤ 65 years.
• Meet the internationally accepted Criteria for the diagnosis of newly diagnosed multiple myeloma (Chinese guidelines for the diagnosis and management of multiple myeloma (revised in 2022) criteria)
• Patients have not received previous anti-multiple myeloma-related chemotherapy, have not received previous extensive pelvic radiotherapy (more than half of the pelvic area), and have not received previous anti-multiple myeloma hormone therapy, except for those who have used hormones for no more than 14 days for symptom control.
• The patient have one or more measurable multiple myeloma lesion, must include one of the 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
• p53 gene abnormalities: Plasma cells were enriched by CD138 immunomagnetic and then detected by FISH. Cut-off ≥20%., or P53 mutation by second-generation sequencing.
• ECOG scores 0 - 1;
• No active infection
• All screening blood biochemistry: tests should be performed according to the protocol and within 14 days before enrollment. Screening laboratory values must meet the following criteria： a.TBIL\<1.5 x upper limit of normal (ULN) (\<3 x ULN in patients with Gilbert's syndrome); b.AST and ALT \<3 x ULN.; c. Creatinine clearance ≥ 60mL/min (calculated using Cockroft-Gault formula).
⁃ normal pulmonary function and oxygen saturation ≥ 92% on room air.
⁃ Routine blood tests (performed within 7 days, no RBC transfusion, no G-CSF/GM-CSF/platelet agonists, no drug correction within 14 days before screening, no PLT 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%)
⁃ Patients must be able to take prophylactic anticoagulant therapy as recommended by the study.
⁃ The woman is not breastfeeding, is not pregnant and agrees not to be pregnant during the study period and for the following 12 months. Male patients agreed that their spouse would not become pregnant during the study period and for 12 months thereafter.
⁃ Willing and able to complete the study procedures and follow-up examinations.