TY - JOUR
T1 - Clinical response and pathway-specific correlates following TIGIT–LAG3 blockade in myeloma
T2 - the MyCheckpoint randomized clinical trial
AU - Richard, Shambavi
AU - Lesokhin, Alexander M.
AU - Paul, Barry
AU - Kaufman, Jonathan L.
AU - Pianko, Matthew
AU - Biran, Noa
AU - Vij, Ravi
AU - Doxie, Deon B.
AU - Azeem, Maryam I.
AU - Martillo, Mercedes
AU - Wozniak, Katie
AU - Cho, Hearn J.
AU - Dhodapkar, Kavita M.
AU - Dhodapkar, Madhav V.
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.
PY - 2024/10
Y1 - 2024/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85202046154&partnerID=8YFLogxK
U2 - 10.1038/s43018-024-00818-w
DO - 10.1038/s43018-024-00818-w
M3 - Article
C2 - 39187595
AN - SCOPUS:85202046154
SN - 2662-1347
VL - 5
SP - 1459
EP - 1464
JO - Nature Cancer
JF - Nature Cancer
IS - 10
ER -