A <scp>CD38</scp> / <scp>CD3xCD28</scp> trispecific T‐cell engager as a potentially active agent in multiple myeloma patients relapsed and/or refractory to anti‐ <scp>CD38</scp> monoclonal antibodies
There is accumulating evidence of BCMA and GPRC5D loss after treatment with T-cell redirecting therapies in patients with relapsed/refractory multiple myeloma (RRMM). While complete CD38 loss is not observed upon relapses after treatment with anti-CD38 monoclonal antibodies (mAb), there is downregulation of surface CD38 expression and decreased number and function of NK cells, which renders these patients resistant to retreatment with anti-CD38 mAb. Here, we provide preclinical evidence that RRMM patients previously exposed to anti-CD38 mAb could benefit from T-cell-based immunotherapy that depend less on CD38 antigen density and NK-cell activity, such as the novel CD38/CD3xCD28 trispecific T-cell engager, SAR442257.
Authors
- Jesús F. San Miguel (ORCID: https://orcid.org/0000-0002-9183-4857)
- Luis‐Esteban Tamariz‐Amador (ORCID: https://orcid.org/0000-0002-4088-0992)
- Marta Lasa (ORCID: https://orcid.org/0000-0002-2981-162X)
- Helgi van de Velde (ORCID: https://orcid.org/0009-0004-4126-8289)
- Bruno Paiva (ORCID: https://orcid.org/0000-0003-1977-3815)
- Laura Blanco (ORCID: https://orcid.org/0000-0002-1859-0884)
- Paula Rodríguez‐Otero (ORCID: https://orcid.org/0000-0001-5236-7785)
- Kamlesh Bisht (ORCID: https://orcid.org/0009-0003-3808-924X)
- Esperanza Martín‐Sánchez (ORCID: https://orcid.org/0000-0002-8155-9185)
- Aintzane Zabaleta (ORCID: https://orcid.org/0000-0003-3474-3040)
- Peter Kim (ORCID: https://orcid.org/0000-0003-4108-299X)
- Hongfang Wang (ORCID: https://orcid.org/0000-0002-1104-1540)
Institutions
- Sanofi (United States) (US)
- Navarre Institute of Health Research (ES)
- Clinica Universidad de Navarra (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
Publication Details
- Journal
- British Journal of Haematology
- Published
- 2024-09-22
- DOI
- https://doi.org/10.1111/bjh.19784
- Citations
- 9
- Primary Topic
- Multiple Myeloma Research and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 4.09
Funders
- Sanofi
- Cancer Research UK
- Universidad de Navarra
- Centro de Investigación Biomédica en Red de Cáncer
- Instituto de Salud Carlos III