{"entity":{"id":"paper-majestec-1-teclistamab-nejm-2022","kind":"paper","name":"MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma","aka":[],"tldr":"A ready-made antibody that pulls T cells onto myeloma cells produced responses in 63% of patients after a median of five prior therapies, without the wait for cell manufacturing.","summary":"MajesTEC-1 was a phase 1/2 single-arm study of teclistamab, a BCMA x CD3 bispecific T-cell engager given subcutaneously weekly after step-up dosing, in 165 patients with relapsed or refractory multiple myeloma who were triple-class exposed (median five prior lines). The overall response rate was 63%, with complete response or better in 39.4%; median duration of response was 18.4 months and median PFS 11.3 months. Cytokine release syndrome occurred in 72% (almost all grade 1-2) and neurotoxicity in about 14.5%, but infections were frequent (grade 3-4 in about 45%) and hypogammaglobulinaemia was near universal. Teclistamab received accelerated approval in 2022, the first bispecific for myeloma.","asOf":"2026-09-08","links":[{"label":"Full text (DOI)","url":"https://doi.org/10.1056/NEJMoa2203478"},{"label":"ClinicalTrials.gov NCT04557098","url":"https://clinicaltrials.gov/study/NCT04557098"}],"tags":[],"related":["bispecific-infection-prophylaxis","bcma-then-gprc5d","paper-magnetismm-3-elranatamab-natmed-2023"],"cancers":["multiple-myeloma"],"sections":[],"technologies":["bispecific-antibody","t-cell-engager"],"targets":["bcma","cd3"],"drugs":["teclistamab","talquetamab","elranatamab"],"companies":["johnson-johnson"],"institutions":[],"pathways":[],"terms":["crs","orr"],"trials":["majestec-1","majestec-3"],"people":[],"bottlenecks":["b-toxicity-qol","b-dose-optimisation"],"keyPapers":[],"journals":["nejm"],"dependsOn":[],"notes":[],"journal":"New England Journal of Medicine","year":2022,"doi":"10.1056/NEJMoa2203478","authors":"Moreau P, Garfall AL, van de Donk NWCJ, et al.","paperType":"translational","findings":["165 triple-class-exposed patients; median 5 prior lines.","Overall response 63.0%; complete response or better 39.4%; MRD-negativity in 26.7% of all patients.","Median duration of response 18.4 months; median PFS 11.3 months.","CRS 72.1% (grade 3 0.6%); neurotoxicity 14.5% (ICANS 3%).","Infections 76.4% (grade 3-4 44.8%); 5 COVID-19 deaths; hypogammaglobulinaemia common."],"whatItMeans":"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.","caveats":["Single-arm study; MajesTEC-3 later provided randomised evidence in earlier lines.","Continuous weekly dosing until progression in the original protocol; optimal duration and schedule still being defined.","Infection-related deaths were substantial; many patients were treated during the COVID-19 pandemic.","Responses are shorter than with cilta-cel, and BCMA-directed sequencing (CAR-T then bispecific or vice versa) reduces subsequent efficacy."],"changedPractice":true,"participants":165},"route":"/key-papers/paper-majestec-1-teclistamab-nejm-2022/","neighbours":{"pairing":[{"id":"bcma-then-gprc5d","kind":"pairing","name":"BCMA-directed therapy → GPRC5D-directed therapy","route":"/pairings/bcma-then-gprc5d/"},{"id":"bispecific-infection-prophylaxis","kind":"pairing","name":"Caution: T-cell redirectors and infections","route":"/pairings/bispecific-infection-prophylaxis/"}],"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/"}],"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/"}],"technology":[{"id":"bispecific-antibody","kind":"technology","name":"Bispecific antibodies","route":"/technologies/bispecific-antibody/"},{"id":"t-cell-engager","kind":"technology","name":"T-cell engagers (bispecific)","route":"/technologies/t-cell-engager/"}],"target":[{"id":"bcma","kind":"target","name":"BCMA","route":"/targets/bcma/"},{"id":"cd3","kind":"target","name":"CD3","route":"/targets/cd3/"}],"drug":[{"id":"elranatamab","kind":"drug","name":"Elranatamab","route":"/drugs/elranatamab/"},{"id":"talquetamab","kind":"drug","name":"Talquetamab","route":"/drugs/talquetamab/"},{"id":"teclistamab","kind":"drug","name":"Teclistamab","route":"/drugs/teclistamab/"}],"company":[{"id":"johnson-johnson","kind":"company","name":"Johnson & Johnson","route":"/companies/johnson-johnson/"}],"term":[{"id":"crs","kind":"term","name":"Cytokine release syndrome (CRS)","route":"/terms/crs/"},{"id":"orr","kind":"term","name":"Objective response rate (ORR)","route":"/terms/orr/"}],"trial":[{"id":"majestec-1","kind":"trial","name":"MajesTEC-1","route":"/trials/majestec-1/"},{"id":"majestec-3","kind":"trial","name":"MajesTEC-3","route":"/trials/majestec-3/"}],"bottleneck":[{"id":"b-toxicity-qol","kind":"bottleneck","name":"Toxicity and quality of life are undervalued","route":"/bottlenecks/b-toxicity-qol/"},{"id":"b-dose-optimisation","kind":"bottleneck","name":"Wrong doses","route":"/bottlenecks/b-dose-optimisation/"}],"journal":[{"id":"nejm","kind":"journal","name":"New England Journal of Medicine","route":"/journals/nejm/"}],"person":[{"id":"philippe-moreau","kind":"person","name":"Philippe Moreau","route":"/people/philippe-moreau/"}]}}