{"entity":{"id":"bispecific-infection-prophylaxis","kind":"pairing","name":"Caution: T-cell redirectors and infections","aka":[],"tldr":"Myeloma bispecifics and CAR-T suppress antibody production so profoundly that infections, not the cancer, became a leading cause of death in early trials.","summary":"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.","asOf":"2026-09-07","links":[{"label":"MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma (New England Journal of Medicine 2022)","url":"https://doi.org/10.1056/NEJMoa2203478"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":[],"technologies":[],"targets":[],"drugs":["teclistamab","elranatamab","linvoseltamab"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"teclistamab","b":"crs","rationale":"BCMA is expressed on normal plasma cells; continuous T-cell engagement causes T-cell exhaustion and profound humoral immunodeficiency.","evidence":"Consistent across MajesTEC-1, MagnetisMM-3, LINKER-MM1; lower with GPRC5D agents.","pairingType":"caution"},"route":"/pairings/bispecific-infection-prophylaxis/","neighbours":{"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"myeloma-relapsed-refractory","kind":"cancer","name":"Relapsed or refractory multiple myeloma","route":"/cancers/myeloma-relapsed-refractory/"}],"drug":[{"id":"elranatamab","kind":"drug","name":"Elranatamab","route":"/drugs/elranatamab/"},{"id":"linvoseltamab","kind":"drug","name":"Linvoseltamab","route":"/drugs/linvoseltamab/"},{"id":"teclistamab","kind":"drug","name":"Teclistamab","route":"/drugs/teclistamab/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"}],"paper":[{"id":"paper-magnetismm-3-elranatamab-natmed-2023","kind":"paper","name":"MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response","route":"/key-papers/paper-magnetismm-3-elranatamab-natmed-2023/"},{"id":"paper-majestec-1-teclistamab-nejm-2022","kind":"paper","name":"MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma","route":"/key-papers/paper-majestec-1-teclistamab-nejm-2022/"}]}}