Caution: T-cell redirectors and infections
Myeloma bispecifics and CAR-T suppress antibody production so profoundly that infections, not the cancer, became a leading cause of death in early trials.
MajesTEC-1: grade 3+ infections ~45% with several fatal COVID-19 and pneumonia cases; hypogammaglobulinaemia near-universal. IVIG replacement, antiviral and PJP prophylaxis, vaccination, and response-adapted dose de-intensification (every 2-4 weeks) are now standard.
Elranatamab confirmed that BCMA bispecifics are a class, not a one-off, and its protocol-built dose reduction after response set a precedent for lowering the immunosuppressive burden of T-cell engagers. Patients now have two approved BCMA bispecifics and one against GPRC5D (talquetamab). Choosing between them, and sequencing them with CAR-T, remains guided by availability and toxicity profile rather than head-to-head data.
Teclistamab showed that an off-the-shelf bispecific can approach CAR-T-like response rates in late myeloma, giving patients who cannot wait for or access cell therapy a real option. It also exposed the price: prolonged T-cell engagement causes profound immunosuppression, so infection prophylaxis and immunoglobulin replacement are now routine. Less frequent dosing after response is being adopted to reduce this burden.