{"entity":{"id":"bcma-then-gprc5d","kind":"pairing","name":"BCMA-directed therapy → GPRC5D-directed therapy","aka":[],"tldr":"When a BCMA drug stops working, switching to a drug against a different myeloma protein still produces responses in about two-thirds of patients.","summary":"When a BCMA-directed therapy such as teclistamab stops working in multiple myeloma, switching to the GPRC5D-directed bispecific talquetamab is a sequence pairing that still produces responses in a majority of patients. GPRC5D is an independent antigen with different escape mechanisms, so antigen loss through TNFRSF17 deletion, which drives resistance to BCMA agents, does not affect it; T-cell fitness is the limitation the two share. The evidence comes from the cohort of MonumenTAL-1 that enrolled patients previously treated with T-cell redirection, and the RedirecTT-1 combination of teclistamab with talquetamab has shown high response rates including in extramedullary disease. The data are phase 1/2 and phase 3 combination trials are ongoing; the MajesTEC-1 paper on teclistamab links here.","asOf":"2026-09-07","links":[{"label":"ClinicalTrials.gov NCT04634552: MonumenTAL-1","url":"https://clinicaltrials.gov/study/NCT04634552"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":[],"technologies":[],"targets":["bcma","gprc5d"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":["monumental-1"],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"a":"teclistamab","b":"talquetamab","rationale":"Independent antigen; different escape mechanisms; T-cell fitness is the shared limitation.","evidence":"Phase 1/2 cohorts; phase 3 combinations ongoing.","pairingType":"sequence"},"route":"/pairings/bcma-then-gprc5d/","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/"}],"target":[{"id":"bcma","kind":"target","name":"BCMA","route":"/targets/bcma/"},{"id":"gprc5d","kind":"target","name":"GPRC5D","route":"/targets/gprc5d/"}],"trial":[{"id":"monumental-1","kind":"trial","name":"MonumenTAL-1","route":"/trials/monumental-1/"}],"drug":[{"id":"talquetamab","kind":"drug","name":"Talquetamab","route":"/drugs/talquetamab/"},{"id":"teclistamab","kind":"drug","name":"Teclistamab","route":"/drugs/teclistamab/"}],"paper":[{"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/"}]}}