Dual-Target BCMA-CD19 CAR-T Cell Therapy for Relapsed / Refractory Multiple Myeloma With Extramedullary Infiltration

Patients must have relapsed or refractory multiple myeloma per IMWG criteria, with measurable extramedullary lesions attributable to multiple myeloma. This is the defining eligibility requirement. Extramedullary disease may include soft-tissue plasmacytomas, organ infiltration, or lesions arising from bone but extending into surrounding soft tissue.

BCMA positivity must be confirmed either by flow cytometry of bone marrow or cerebrospinal fluid tumour cells, or by immunohistochemistry of tumour tissue. This is a hard eligibility requirement — BCMA-negative myeloma would not be expected to respond to the BCMA component of the dual CAR construct.

Per IMWG relapsed/refractory criteria, patients must have progressed after treatment with available standard therapies. Given the focus on heavily pre-treated RRMM with extramedullary disease, patients who have received prior proteasome inhibitors, immunomodulatory drugs, anti-CD38 antibodies, and potentially prior BCMA-targeted bispecific antibodies or single-target BCMA CAR-T are expected to be in this population.

Patients who have received a previous CAR-T product with the same vector structure as the product being used in this trial are excluded. Importantly, this exclusion specifies the same vector structure — not all prior CAR-T therapy. Patients who received prior BCMA CAR-T with a different vector structure (e.g., ide-cel vs. cilta-cel vs. investigational Chinese products) may remain eligible, subject to investigator assessment. ⚠ VERIFY: Confirm the specific vector identity with the trial team.

ECOG performance status of 0, 1, or 2 is required. Organ function thresholds: LVEF > 50% (echo within 2 weeks); ALT/AST < 3× ULN; creatinine clearance ≥ 40 mL/min; FEV1% predicted ≥ 50%; SpO₂ > 95%. Life expectancy > 3 months required.

Age range 18–75 years. Patients with active uncontrolled infections, active uncontrolled autoimmune disease, active GVHD (post-allogeneic transplant), or positive HBV/HCV/HIV/syphilis serology are excluded.

BCMA downregulation is one of the most common mechanisms of relapse after anti-BCMA CAR-T therapy. By simultaneously targeting CD19 — which is expressed on a different, precursor cell population not targeted by BCMA — the dual approach is designed to remain active even if BCMA expression decreases on myeloma cells.

The CD19 component targets B-cell precursors — the upstream reservoir that is believed to continuously seed new myeloma plasma cells. Eliminating this precursor pool alongside mature myeloma cells via the BCMA component may extend remission duration by addressing the source of relapse, not just the current disease.

KQ-2003 (ASH 2024) — a BCMA/CD19 dual-target CAR-T with similar dual-targeting rationale — demonstrated 100% hematological ORR and 88.9% CR/sCR rate in 18 evaluable RRMM patients, with 60.9% having EMD at baseline and described promising, persistent anti-EMD efficacy in the extramedullary subgroup.

GC012F, another BCMA/CD19 dual CAR-T product with next-day manufacturing, demonstrated 93% ORR with 89.6% achieving VGPR or better, and a median duration of response of 38 months — among the most durable responses published in the heavily pre-treated RRMM setting.

AZD0120 (DURGA-1, 2025) — a dual BCMA/CD19 CAR-T — demonstrated 100% ORR in 5 patients with prior BCMA-targeted CAR-T exposure, with 80% CR/sCR rate. This suggests dual-target BCMA-CD19 CAR-T may rescue patients who have progressed after single-target BCMA CAR-T — a critical clinical application.

The trial operates across Beijing GoBroad Hospital (China's highest-volume CAR-T centre) and two prestigious Shanghai institutions — Shanghai Liquan Hospital and Ruijin Hospital (affiliated with Shanghai Jiao Tong University School of Medicine). This provides access to a high-volume, experienced CAR-T team across multiple sites.