CELL INTELLIGENCE · 肿瘤细胞治疗研究

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 75 years.
2. Participants with documented newly-diagnosed multiple myeloma according to IMWG diagnostic criteria.
3. Measurable disease at screening, defined as: Serum M-protein level ≥1.0 g/dL or urine M-protein level ≥200 mg/24 hours; or Light chain MM without measurable disease in serum or urine: serum Ig free-light chain (FLC) ≥10 mg/dL and abnormal serum Ig kappa lambda FLC ratio.
4. Patients deemed ineligible for high-dose chemotherapy with ASCT due to any of the following: Age ≥65 years; Investigator assessment of ineligibility; ECOG performance status 3-4; Repeated failure of hematopoietic stem cell mobilization; Patient's decision to defer ASCT.
5. Tumor cells were BCMA and GPRC5D positive.
6. Serum total bilirubin \<2 x upper limit of normal (ULN), serum AST and ALT \<3 x ULN, creatinine clearance ≥ 30mL/min (Cockroft-Gault formula).
7. Informed Consent/Assent: All subjects have the ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

1. Active amyloidosis.
2. Central nervous system involvement.
3. Prior BCMA-targeted therapy or CAR-T therapy.
4. Active hepatitis B or hepatitis C virus infection.
5. Known HIV infection.
6. Life expectancy \<6 months.
7. Woman who are pregnant or breastfeeding.
8. Evidence of uncontrolled dysfunction of heart, lung, brain, and other important organs.
9. Any other conditions that are not eligible for the trial in the judgement of the principal investigator.

主要终点：Sustained MRD-negative rate · Rate of patients achieving sustained MRD negativity for more than 12 months · Up to 2 year；Progression free survival (PFS) · Progression free survival is defined as the time from the date of diagnosis to the date of first documented PD, as defined in the IMWG criteria, or death due to any cause, whichever occurs first · Up to 3 year
次要终点：Complete response rate (CRR)；MRD negativity rate；Overall survival (OS)

• Standard-risk · EXPERIMENTAL · Enrolled patients will be stratified into standard-risk group based on the absence of ultra-high-risk features, defined as: (1) double-hit cytogenetics, (2) presence of extramedullary disease, or (3) circulating tumor cells (CTCs) ≥2%. Patients in the standard-risk group will receive BCMA CAR-T therapy after standard induction, followed by standard consolidation and maintenance. Patients achieving sustained MRD negativity and stringent complete response (sCR) on two consecutive assessments may enter a treatment-free observation phase. Patients who experience MRD resurgence or loss of response will resume maintenance therapy.
• Ultra high risk · EXPERIMENTAL · Enrolled patients will be stratified into an ultra-high-risk group based on the presence of ultra-high-risk features, defined as: (1) double-hit cytogenetics, (2) presence of extramedullary disease, or (3) circulating tumor cells (CTCs) ≥2%. Patients in the ultra-high-risk group will also receive BCMA CAR-T therapy after induction, followed by GPRC5D/CD3 bispecific antibody consolidation and maintenance. Patients achieving sCR and sustained MRD negativity (≥12 months) may enter treatment-free observation, while those with MRD resurgence or loss of response will resume maintenance therapy.

This is a prospective, single-center, clinical study to evaluate the efficacy and safety of a fully immunotherapy-based strategy guided by MRD-driven dynamic risk stratification in transplant-ineligible patients with newly diagnosed multiple myeloma.