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

doi:10.1038/s43018-024-00818-w

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

School of Medicine

Icahn School of Medicine at Mount Sinai
Memorial Sloan-Kettering Cancer Center
Levine Cancer Institute
Emory University
University of Michigan, Ann Arbor
Washington University St. Louis
Multiple Myeloma Research Foundation

Research output: Contribution to journal › Article › peer-review

23 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 language	English
Pages (from-to)	1459-1464
Number of pages	6
Journal	Nature Cancer
Volume	5
Issue number	10
DOIs	https://doi.org/10.1038/s43018-024-00818-w
State	Published - Oct 2024

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SDG 3 Good Health and Well-being

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10.1038/s43018-024-00818-w

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Richard, S., Lesokhin, A. M., Paul, B., Kaufman, J. L., Pianko, M., Biran, N., Vij, R., Doxie, D. B., Azeem, M. I., Martillo, M., Wozniak, K., Cho, H. J., Dhodapkar, K. M., & Dhodapkar, M. V. (2024). Clinical response and pathway-specific correlates following TIGIT–LAG3 blockade in myeloma: the MyCheckpoint randomized clinical trial. Nature Cancer, 5(10), 1459-1464. https://doi.org/10.1038/s43018-024-00818-w

@article{8719b4bb693c4508a8c167348d8b09da,

title = "Clinical response and pathway-specific correlates following TIGIT{\textendash}LAG3 blockade in myeloma: the MyCheckpoint randomized clinical trial",

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{\textendash}LAG3 blockade and identify pathway-specific response correlates in myeloma.",

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

note = "Publisher Copyright: {\textcopyright} The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.",

year = "2024",

month = oct,

doi = "10.1038/s43018-024-00818-w",

language = "English",

volume = "5",

pages = "1459--1464",

journal = "Nature Cancer",

issn = "2662-1347",

publisher = "Nature Research",

number = "10",

}

Richard, S, Lesokhin, AM, Paul, B, Kaufman, JL, Pianko, M, Biran, N, Vij, R, Doxie, DB, Azeem, MI, Martillo, M, Wozniak, K, Cho, HJ, Dhodapkar, KM & Dhodapkar, MV 2024, 'Clinical response and pathway-specific correlates following TIGIT–LAG3 blockade in myeloma: the MyCheckpoint randomized clinical trial', Nature Cancer, vol. 5, no. 10, pp. 1459-1464. https://doi.org/10.1038/s43018-024-00818-w

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.

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 - https://www.scopus.com/pages/publications/85202046154

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AN - SCOPUS:85202046154

SN - 2662-1347

VL - 5

SP - 1459

EP - 1464

JO - Nature Cancer

JF - Nature Cancer

IS - 10

ER -

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

Abstract

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