# BCMA-directed therapy → GPRC5D-directed therapy

Source: https://onco.cc/pairings/bcma-then-gprc5d/  
OnCo record `bcma-then-gprc5d` (Pairing). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Pairing
- Last checked: 2026-09-07
- Pairs: Teclistamab + Talquetamab
- Type: sequence
- Rationale: Independent antigen; different escape mechanisms; T-cell fitness is the shared limitation.
- Evidence: Phase 1/2 cohorts; phase 3 combinations ongoing.

## Sources

- ClinicalTrials.gov NCT04634552: MonumenTAL-1: https://clinicaltrials.gov/study/NCT04634552

## Connected records

- cancers: [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Relapsed or refractory multiple myeloma](https://onco.cc/cancers/myeloma-relapsed-refractory/)
- targets: [BCMA](https://onco.cc/targets/bcma/), [GPRC5D](https://onco.cc/targets/gprc5d/)
- trials: [MonumenTAL-1](https://onco.cc/trials/monumental-1/)
- drugs: [Talquetamab](https://onco.cc/drugs/talquetamab/), [Teclistamab](https://onco.cc/drugs/teclistamab/)
- key papers: [MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma](https://onco.cc/key-papers/paper-majestec-1-teclistamab-nejm-2022/)

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