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. 2024 Dec;205(6):2262-2267.
doi: 10.1111/bjh.19784. Epub 2024 Sep 22.

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

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
Affiliations

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

Aintzane Zabaleta et al. Br J Haematol. 2024 Dec.

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.

Keywords: CD38; T‐cell engager; antibody therapy; relapsed/refractory multiple myeloma; resistance to anti‐CD38 monoclonal antibodies.

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References

REFERENCES

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