MRD‑guided BCMA CAR-T with optional GPRC5D/CD3 BiTE consolidation for transplant‑ineligible newly diagnosed multiple myeloma

A Prospective, Open-Label, Single-Center Clinical Study of a Fully Immunotherapy-Based Strategy Driven by MRD-Guided Dynamic Risk Stratification in Transplant-Ineligible Newly Diagnosed Multiple Myeloma

This trial will try MRD‑guided immunotherapy using BCMA CAR‑T for adults newly diagnosed with multiple myeloma who cannot have a transplant, adding a GPRC5D/CD3 bispecific antibody for those at very high risk.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, immunotherapy
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07106736 on ClinicalTrials.gov

What this trial studies

All participants receive up to four cycles of standard induction therapy, followed by response assessment and enrollment if they meet eligibility. Patients are stratified by predefined clinical and molecular features into standard‑risk and ultra‑high‑risk groups. Both groups receive BCMA‑directed CAR‑T; standard‑risk patients proceed to standard consolidation and maintenance while ultra‑high‑risk patients receive additional GPRC5D/CD3 bispecific antibody consolidation and maintenance. Those who achieve and sustain MRD negativity and stringent complete response may enter a treatment‑free observation phase, and any MRD resurgence prompts resumption of maintenance.

Who should consider this trial

Good fit: Adults 18–75 years with newly diagnosed, measurable multiple myeloma who are ineligible for autologous stem cell transplant and whose tumor cells express BCMA and GPRC5D, with adequate liver and kidney function, are the intended participants.

Not a fit: Patients who are eligible for transplant, have inadequate organ function, lack BCMA or GPRC5D expression, or cannot tolerate immunotherapy are unlikely to benefit from this approach.

Why it matters

Potential benefit: If successful, this approach could produce deeper, longer remissions and allow some transplant‑ineligible patients to have prolonged treatment‑free periods.

How similar studies have performed: BCMA‑targeted CAR‑T therapies have shown high response rates in relapsed/refractory myeloma, but using MRD‑adaptive CAR‑T frontline and sequencing with a GPRC5D/CD3 bispecific antibody in transplant‑ineligible newly diagnosed patients is relatively novel and not yet proven.

Eligibility criteria

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.

Where this trial is running

Tianjin, Tianjin Municipality

• Institute of Hematology and Blood Diseases Hospital Chinese Academy of Medical Sciences — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Study coordinator: Gang An, PhD&MD

Conditions Multiple Myeloma, Newly Diagnosed; Multiple myeloma; MRD; CAR-T; BiTEs