# MajesTEC-1: teclistamab, an off-the-shelf BCMA bispecific antibody, in heavily pretreated myeloma

Source: https://onco.cc/key-papers/paper-majestec-1-teclistamab-nejm-2022/  
OnCo record `paper-majestec-1-teclistamab-nejm-2022` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2022
- DOI: 10.1056/NEJMoa2203478
- Authors: Moreau P, Garfall AL, van de Donk NWCJ, et al.
- 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.
- What it means: 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.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa2203478
- ClinicalTrials.gov NCT04557098: https://clinicaltrials.gov/study/NCT04557098

## Connected records

- pairings: [BCMA-directed therapy → GPRC5D-directed therapy](https://onco.cc/pairings/bcma-then-gprc5d/), [Caution: T-cell redirectors and infections](https://onco.cc/pairings/bispecific-infection-prophylaxis/)
- key papers: [MagnetisMM-3: elranatamab, a second BCMA bispecific, with a switch to fortnightly dosing after response](https://onco.cc/key-papers/paper-magnetismm-3-elranatamab-natmed-2023/)
- cancers: [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Relapsed or refractory multiple myeloma](https://onco.cc/cancers/myeloma-relapsed-refractory/)
- technologies: [Bispecific antibodies](https://onco.cc/technologies/bispecific-antibody/), [T-cell engagers (bispecific)](https://onco.cc/technologies/t-cell-engager/)
- targets: [BCMA](https://onco.cc/targets/bcma/), [CD3](https://onco.cc/targets/cd3/)
- drugs: [Elranatamab](https://onco.cc/drugs/elranatamab/), [Talquetamab](https://onco.cc/drugs/talquetamab/), [Teclistamab](https://onco.cc/drugs/teclistamab/)
- companies: [Johnson & Johnson](https://onco.cc/companies/johnson-johnson/)
- terms: [Cytokine release syndrome (CRS)](https://onco.cc/terms/crs/), [Objective response rate (ORR)](https://onco.cc/terms/orr/)
- trials: [MajesTEC-1](https://onco.cc/trials/majestec-1/), [MajesTEC-3](https://onco.cc/trials/majestec-3/)
- bottlenecks: [Toxicity and quality of life are undervalued](https://onco.cc/bottlenecks/b-toxicity-qol/), [Wrong doses](https://onco.cc/bottlenecks/b-dose-optimisation/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- people: [Philippe Moreau](https://onco.cc/people/philippe-moreau/)

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