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

Summary 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.