Concurrent administration of BCMA and GPRC5D CAR T cells for advanced multiple myeloma.
Sham Mailankody, Sneha Mitra, Kevin Herrera et al.
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In 30 seconds
This phase 1 dose-escalation trial evaluated BCMA-directed CAR T-cell therapy MCARH125 alone or infused concurrently with GPRC5D-directed MCARH109 in patients with relapsed or refractory multiple myeloma. Fifteen patients were treated: 6 received MCARH125 alone and 9 received the dual-cell infusion. The primary objective was to assess the safety of concurrent infusion. Among patients receiving both CAR T-cell products, the overall response was 78%, and median progression-free survival was 18.2 months. No grade ≥3 cytokine release syndrome or immune effector cell-associated neurologic syndrome occurred.
Key findings
- Among 9 patients receiving concurrent MCARH125 and MCARH109, the overall response was 78%, with median progression-free survival of 18.2 months.
- One patient in each treatment group developed immune effector cell-associated hemophagocytic syndrome; no grade ≥3 cytokine release syndrome or neurologic syndrome occurred.
- Dual-CAR recipients had significantly less BCMA CAR expansion than patients receiving BCMA CAR alone, despite equivalent BCMA CAR T-cell doses at infusion.
- Correlative analyses suggested antigen loss may contribute to resistance despite targeting two antigens.
Why it matters
The trial provides early clinical evidence on the feasibility and activity of concurrently targeting BCMA and GPRC5D in relapsed or refractory myeloma. Its findings also highlight that dual-antigen targeting may not prevent antigen-loss resistance and that expansion of one CAR population could affect the other, considerations relevant to interpreting efficacy and designing further studies.
What to keep in mind
This was a phase 1 dose-escalation trial with 15 patients overall, including 9 treated with concurrent CAR T cells; the small sample limits the precision and generalisability of efficacy and safety findings.