A Single-arm Prospective Study of the Treatment in High-risk Newly Diagnosed Multiple Myeloma With Minimal Residual Disease Detection
The goal of this study is to evaluate sustained MRD negativity for one year in DKRD induction \& consolidation therapy +/- ASCT in newly diagnosed high-risk multiple myeloma patients. It aims to evaluate the efficacy and safety of the combination regimen of Daratumumab in combination with carfilzomib, lenalidomide, and dexamethasone (DKRD) +/- ASCT for the treatment of patients with newly diagnosed high-risk multiple myeloma. Participants will receive bortezomib based induction therapy for one cycle, and then DKRD induction for 3 cycles(+ASCT), DKRD consolidation for 2-4 cycles, and DKR maintenance treatment(adjusted according to MRD negativity after consolidation therapy)
• patients with newly diagnosed multiple myeloma（may receive up to one course of a bortezomib-containing regimen for the urgent relief of bone pain, renal insufficiency, and hypercalcemia）;
• age ≥ 18 years;
• have an evaluable lesion; serum M protein ≥ 10 g/L, or urinary light chain ≥ 200 mg/24h, or involved serum free light chain (FLC) ≥ 100 mg/L, and an extramedullary measurable tumor SPD: The diameter of cutaneous nodules can be measured with a manual tape, and extramedullary tumor SPD of extramedullary tumors is measured on a CT scan as the product of the largest dimension of the largest pendulous diameter of the lesion (minimum diameter of 5mm or more), parosteal lesions need to be in soft tissue outside the bone cavity to meet the above criteria. MRI measures the size of an extramedullary tumor as the product of the maximum pendulous diameter at the level of the largest area of the tumor (minimum diameter of 5mm or more)
• ECOG physical status score ≤ 2
• or have a high-risk karyotype abnormality recognized in mSMART or NCCN guidelines: t(4;14), t(14;16), t(14;20), Del(17p) or -17 and/or TP53 mutation, Del(1p32), 1q21 gain(amp), the coexistence of two adverse karyotypes as a double hit,and triple hit similarly defined
• or R-ISS stage 3
• or combined plasma cell leukemia (defined as peripheral blood sorted clonal plasma cells ≥ 5%)
• bone marrow function: neutrophils ≥ 1.0 x 109 /L, platelets ≥ 70 x 109 /L (if bone marrow plasma cells ≥ 50%, platelets ≥ 50 x 109 /L)
• AST, ALT, ALP ≤ 3 × upper limit of normal value, serum bilirubin ≤ 2 times upper limit of normal value;
⁃ serum creatinine clearance ≥ 40mL/min
⁃ negative pregnancy test for women of childbearing age; patients and their spouses must agree to use effective contraception during the treatment period and the following one-year period;
⁃ Signed informed consent for chemotherapy. A legal representative will sign the informed consent form if the subject is unable to sign it due to impaired consciousness, paralysis of the subject's upper limbs, or inability to write.