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

Nat Cancer. 2024 Oct;5(10):1459-1464. doi: 10.1038/s43018-024-00818-w. Epub 2024 Aug 26.

Authors

Shambavi Richard^#¹, Alexander M Lesokhin^#², Barry Paul^#³, Jonathan L Kaufman⁴, Matthew Pianko⁵, Noa Biran⁶, Ravi Vij⁷, Deon B Doxie⁴, Maryam I Azeem⁴, Mercedes Martillo⁸, Katie Wozniak⁸, Hearn J Cho^{1

8}, Kavita M Dhodapkar^{9

10}, Madhav V Dhodapkar¹¹

Affiliations

¹ Tisch Cancer Institute, Icahn School of Medicine, New York, NY, USA.
² Memorial Sloan Kettering Cancer Center, New York, NY, USA.
³ Levine Cancer Institute, Charlotte, NC, USA.
⁴ Winship Cancer Institute, Emory University, Atlanta, GA, USA.
⁵ University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA.
⁶ John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ, USA.
⁷ Washington University School of Medicine, St. Louis, MO, USA.
⁸ The Multiple Myeloma Research Foundation, Norwalk, CT, USA.
⁹ Winship Cancer Institute, Emory University, Atlanta, GA, USA. kavita.dhodapkar@emory.edu.
¹⁰ Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, and Department of Pediatric Hematology/Oncology, Emory University, Atlanta, GA, USA. kavita.dhodapkar@emory.edu.
¹¹ Winship Cancer Institute, Emory University, Atlanta, GA, USA. madhav.v.dhodapkar@emory.edu.

^# Contributed equally.

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.

Publication types

Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Adult
Aged
Antigens, CD*
Antigens, Differentiation, T-Lymphocyte
Antineoplastic Combined Chemotherapy Protocols / therapeutic use
Dexamethasone* / administration & dosage
Dexamethasone* / therapeutic use
Female
Humans
Killer Cells, Natural / drug effects
Killer Cells, Natural / immunology
Lymphocyte Activation / drug effects
Lymphocyte Activation Gene 3 Protein*
Male
Middle Aged
Multiple Myeloma* / drug therapy
Multiple Myeloma* / immunology
Receptors, Immunologic* / antagonists & inhibitors
T Lineage-Specific Activation Antigen 1
Thalidomide / administration & dosage
Thalidomide / analogs & derivatives
Thalidomide / therapeutic use
Treatment Outcome

Substances

TIGIT protein, human
Lymphocyte Activation Gene 3 Protein
Receptors, Immunologic
Lag3 protein, human
Dexamethasone
Antigens, CD
pomalidomide
Thalidomide
Antigens, Differentiation, T-Lymphocyte
T Lineage-Specific Activation Antigen 1

Associated data

ClinicalTrials.gov/NCT04150965

Abstract

Publication types

MeSH terms

Substances

Associated data

Grants and funding