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Myeloma bispecifics and CAR-T suppress antibody production so profoundly that infections, not the cancer, became a leading cause of death in early trials.
This caution pairing records that BCMA-directed T-cell redirectors in multiple myeloma, teclistamab, elranatamab and linvoseltamab, suppress antibody production so profoundly that infections rather than the cancer became a leading cause of death in early trials. BCMA is expressed on normal plasma cells, and continuous T-cell engagement causes T-cell exhaustion and deep humoral immunodeficiency; in MajesTEC-1 severe infections were frequent, including fatal COVID-19 and pneumonia, and hypogammaglobulinaemia was almost universal. The pattern held across MajesTEC-1, MagnetisMM-3 and LINKER-MM1 and is less marked with GPRC5D agents. Immunoglobulin replacement, antiviral and PJP prophylaxis, vaccination, and response-adapted dosing every two to four 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.
Shares Elranatamab, MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares Linvoseltamab, MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma, Teclistamab, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma, Teclistamab, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma, Teclistamab, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares Linvoseltamab, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares Linvoseltamab, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares Linvoseltamab, Elranatamab, Teclistamab, Relapsed or refractory multiple myeloma.