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