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. 2023 Nov;4(11):1536-1543.
doi: 10.1038/s43018-023-00625-9. Epub 2023 Aug 31.

Acquired resistance to a GPRC5D-directed T-cell engager in multiple myeloma is mediated by genetic or epigenetic target inactivation

Jennifer Derrien #  1 , Sarah Gastineau #  1 , Antoine Frigout  1 , Nils Giordano  1 , Mia Cherkaoui  1 , Victor Gaborit  1   2 , Rémi Boinon  1 , Elise Douillard  1   2 , Magali Devic  1   2 , Florence Magrangeas  1   2 , Philippe Moreau  1   3 , Stéphane Minvielle  1   2 , Cyrille Touzeau  1   3 , Eric Letouzé  4   5
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Acquired resistance to a GPRC5D-directed T-cell engager in multiple myeloma is mediated by genetic or epigenetic target inactivation

Jennifer Derrien et al. Nat Cancer. 2023 Nov.

Erratum in

Abstract

Bispecific antibodies targeting GPRC5D demonstrated promising efficacy in multiple myeloma, but acquired resistance usually occurs within a few months. Using a single-nucleus multi-omic strategy in three patients from the MYRACLE cohort (ClinicalTrials.gov registration: NCT03807128 ), we identified two resistance mechanisms, by bi-allelic genetic inactivation of GPRC5D or by long-range epigenetic silencing of its promoter and enhancer regions. Molecular profiling of target genes may help to guide the choice of immunotherapy and early detection of resistance in multiple myeloma.

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References

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