High‑dose transplant with BCMA CAR‑T followed by GPRC5D/CD3 bispecific antibody maintenance for ultra‑high‑risk newly diagnosed multiple myeloma

A Prospective, Single-Arm, Phase II Study of Autologous Stem Cell Transplantation Combined With BCMA CAR-T Therapy Followed by GPRC5D/CD3 Bispecific Antibody Maintenance in Transplant-Eligible Patients With Ultra-High-Risk Multiple Myeloma

This trial will test whether combining autologous stem‑cell transplant, BCMA CAR‑T cells, and GPRC5D/CD3 bispecific antibody maintenance helps people under 70 with newly diagnosed ultra‑high‑risk multiple myeloma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: Institute of Hematology & Blood Diseases Hospital, China (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT07106710 on ClinicalTrials.gov

What this trial studies

This is a prospective, single‑arm phase II protocol for transplant‑eligible adults with newly diagnosed ultra‑high‑risk multiple myeloma. After up to four cycles of standard induction and screening, enrolled patients receive high‑dose chemotherapy with autologous stem cell transplantation combined with BCMA‑targeted CAR‑T infusion, followed by GPRC5D/CD3 bispecific antibody maintenance. Maintenance duration is guided by depth of response and MRD: patients with sCR and sustained MRD negativity (≥12 months) receive 24 months of maintenance then observation, with reinitiation if MRD resurges, while others continue bispecific therapy until progression or unacceptable toxicity. The study is conducted at the Institute of Hematology & Blood Diseases Hospital in Tianjin, China, and requires on‑site procedures and follow‑up.

Who should consider this trial

Good fit: Adults 18–70 with newly diagnosed, transplant‑eligible multiple myeloma who meet ultra‑high‑risk criteria (eg, double‑hit cytogenetics, extramedullary disease, or ≥2% circulating plasma cells) and whose tumor cells express BCMA and GPRC5D are ideal candidates.

Not a fit: Patients older than 70, those ineligible for high‑dose chemotherapy, those whose tumors lack BCMA or GPRC5D expression, or those with severe organ dysfunction or uncontrolled comorbidities may not be suitable or likely to benefit.

Why it matters

Potential benefit: If successful, this approach could produce deeper, longer remissions and may allow some ultra‑high‑risk patients to achieve extended treatment‑free periods.

How similar studies have performed: BCMA CAR‑T therapies and GPRC5D‑targeting bispecific antibodies have shown promising activity in relapsed/refractory myeloma, but the sequential combination with ASCT followed by bispecific maintenance is a novel strategy with limited prior data.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 70 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 eligible for high-dose chemotherapy with ASCT.
5. Presence of at least one of the following ultra-high-risk features: a. Double-hit multiple myeloma, defined as the presence of at least two of the following high-risk cytogenetic abnormalities: t(4;14), t(14;16), deletion 1p, gain 1q, MYC rearrangement, deletion 17p, or TP53 mutation; b. Presence of extramedullary soft tissue plasmacytomas; c. Circulating plasma cells ≥2% in peripheral blood.
6. Tumor cells were BCMA and GPRC5D positive.
7. Serum total bilirubin \<2 x upper limit of normal (ULN), serum AST and ALT \<3 x ULN, creatinine clearance ≥ 30mL/min (Cockroft-Gault formula).
8. 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; Ultra-high-risk; CAR-T; BiTEs; ASCT