Publicaciones científicas

A CD38/CD3xCD28 trispecific T-cell engager as a potentially active agent in multiple myeloma patients relapsed and/or refractory to anti-CD38 monoclonal antibodies

22-sep-2024 | Revista: British Journal of Haematology

Aintzane Zabaleta  1 , Laura Blanco  1 , Peter S Kim  2 , Kamlesh Bisht  2 , Hongfang Wang  2 , Helgi Van de Velde  2 , Marta Lasa  1 , Luis-Esteban Tamariz-Amador  1 , Paula Rodriguez-Otero  1 , Jesús San-Miguel  1 , Bruno Paiva  1 , Esperanza Martín-Sánchez  1


Abstract

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.

CITA DEL ARTÍCULO  Br J Haematol. 2024 Sep 22. doi: 10.1111/bjh.19784