Clinical response and pathway-specific correlates following TIGIT–LAG3 blockade in myeloma: The MyCheckpoint randomized clinical trial Journal Article
| Authors: | 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. |
| Article Title: | Clinical response and pathway-specific correlates following TIGIT–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–LAG3 blockade and identify pathway-specific response correlates in myeloma. © The Author(s), under exclusive licence to Springer Nature America, Inc. 2024. |
| Keywords: | adult; controlled study; treatment outcome; treatment response; aged; middle aged; unclassified drug; thalidomide; drug efficacy; drug safety; antineoplastic agent; cancer immunotherapy; multiple myeloma; randomized controlled trial; antineoplastic combined chemotherapy protocols; creatinine; dexamethasone; drug effect; alanine aminotransferase; aspartate aminotransferase; immunology; lymphocyte activation; cd4+ t lymphocyte; heparin; natural killer cell; killer cells, natural; antigens, cd; drug therapy; fluorescence activated cell sorting; leukocyte antigen; myeloma; receptors, immunologic; programmed death 1 receptor; t lymphocyte antigen; antigens, differentiation, t-lymphocyte; immunoglobulin receptor; lymphocyte activation gene 3 protein; pomalidomide; humans; human; male; female; article; elotuzumab; mass cytometry; tigit protein, human; lymphocyte activation gene 3 protein antibody; t cell immunoreceptor antibody; cd226 antigen; lag3 protein, human |
| Journal Title: | Nature Cancer |
| Volume: | 5 |
| Issue: | 10 |
| ISSN: | 2662-1347 |
| Publisher: | Nature Research |
| Date Published: | 2024-10-01 |
| Start Page: | 1459 |
| End Page: | 1464 |
| Language: | English |
| DOI: | 10.1038/s43018-024-00818-w |
| PUBMED: | 39187595 |
| PROVIDER: | scopus |
| PMCID: | PMC11875007 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Source: Scopus |
