Autologous transplant with BCMA CAR-T followed by GPRC5D/CD3 bispecific antibody maintenance for transplant‑eligible primary plasma cell leukemia

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 Primary Plasma Cell Leukemia

This plan will try combining high‑dose autologous stem cell transplant and BCMA CAR‑T followed by GPRC5D/CD3 bispecific antibody maintenance to see if it improves remission and disease control in transplant‑eligible primary plasma cell leukemia.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 20 (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: NCT07106684 on ClinicalTrials.gov

What this trial studies

This is a prospective, single‑arm Phase II protocol enrolling newly diagnosed, transplant‑eligible primary plasma cell leukemia patients whose tumors express BCMA and GPRC5D. Patients receive up to four cycles of standard induction, then undergo high‑dose chemotherapy with autologous stem cell transplantation combined with BCMA CAR‑T cell infusion. After transplant and CAR‑T, patients receive GPRC5D/CD3 bispecific antibody therapy as maintenance; those achieving stringent complete response with sustained MRD negativity (≥12 months) receive 24 months of maintenance then enter observation, while others continue maintenance until progression or unacceptable toxicity. MRD resurgence during observation triggers resumption of maintenance therapy. The trial is conducted at the Institute of Hematology & Blood Diseases Hospital in Tianjin, China.

Who should consider this trial

Good fit: Adults 18–70 years with newly diagnosed primary plasma cell leukemia who are eligible for high‑dose chemotherapy/ASCT, have measurable disease, adequate organ function, and BCMA and GPRC5D positive tumor expression are the intended candidates.

Not a fit: Patients with prior BCMA‑targeted or CAR‑T therapy, active central nervous system involvement, active amyloidosis, uncontrolled viral hepatitis, non‑expressing BCMA/GPRC5D tumors, or who are not fit for transplant are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this combined approach could deepen remissions, prolong MRD‑negative intervals, and increase the chance of durable, treatment‑free remission for a high‑risk patient group.

How similar studies have performed: BCMA CAR‑T therapies and GPRC5D‑targeting bispecific antibodies have shown promising activity in multiple myeloma, but the specific sequence of ASCT plus CAR‑T followed by BiTE maintenance is a novel combination with limited prior evidence.

Eligibility criteria

Inclusion Criteria:

1. Age ≥ 18 years and ≤ 70 years.
2. Participants with documented newly-diagnosed primary plasma cell leukemia 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. 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, Plasma Cell Leukemia; Plasma cell leukemia; CAR-T; ASCT; BiTEs