Clinical response and pathway-specific correlates following TIGIT–LAG3 blockade in myeloma: the MyCheckpoint randomized clinical trial

Shambavi Richard, Alexander M. Lesokhin, Barry Paul, Jonathan L. Kaufman, Matthew Pianko, Noa Biran, Ravi Vij, Deon B. Doxie, Maryam I. Azeem, Mercedes Martillo, Katie Wozniak, Hearn J. Cho, Kavita M. Dhodapkar, Madhav V. Dhodapkar

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Persons with myeloma were randomized to receive an anti-TIGIT (T cell immunoreceptor) or anti-LAG3 (lymphocyte activation gene) antibody followed by combination with pomalidomide and dexamethasone (NCT04150965). Primary and secondary endpoints were safety and efficacy, respectively. Therapy was well tolerated without dose-limiting toxicity. Durable clinical responses were observed in both the anti-TIGIT(three of six participants) and the anti-LAG3 (two of six participants) arms. Anti-LAG3 responders had higher naive cluster of differentiation 4 (CD4)-positive T cells and lower programmed cell death protein 1-positive effector T cells. Anti-TIGIT responders had higher CD226 expression, natural killer cell activation and lower CD112 expression. These data demonstrate the clinical activity of TIGIT–LAG3 blockade and identify pathway-specific response correlates in myeloma.

Original languageEnglish
Pages (from-to)1459-1464
Number of pages6
JournalNature Cancer
Volume5
Issue number10
DOIs
StatePublished - Oct 2024

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