Multiple myeloma and the potential of new checkpoint inhibitors for immunotherapy

Kamali, Ali N; Hamedifar, Haleh; Eisenhut , Michael; Bautista, Jose M

Multiple myeloma and the potential of new checkpoint inhibitors for immunotherapy

Authors

Kamali, Ali N

Hamedifar, Haleh

Eisenhut , Michael

Bautista, Jose M

Issue Date

2024

Type

Scientific Paper

Keywords

Research Subject Categories::MEDICINE::Dermatology and venerology,clinical genetics, internal medicine::Internal medicine::Paediatric medicine

Abstract

Abstract Multiple myeloma (MM), a cancer of the bone marrow, is categorized as the second most common hematological malignancy of adults in the Western world. Despite dramatic improvements in immunotherapies in the field of cancers, MM immunotherapy has not been promising until now. Recent clinical studies of immune checkpoint inhibitor therapy, either alone or in combination with anticancer drugs, showed excessive side effects or low efficacy, particularly in advanced MM patients. In this context, lymphocyte levels of exhaustion markers play a pivotal role in the MM tumor microenvironment (TME). Hence in the present review, the mechanisms relevant to MM of five inhibitory molecules including T-cell immunoreceptor with Ig and ITIM domains (TIGIT), T-cell immunoglobulin, and mucin domain 3 (Tim-3), lymphocyte activation gene-3 (LAG-3), V-domain Ig Suppressor of T-cell activation and killer immunoglobulin-like receptors along with bispecific T-cell antibodies (BsAbs) will be discussed. Further, we summarized the underlying biology of these checkpoints in cancer and their rapidly emerging role in pathways in MM along with presenting recent clinical trials in context. Keywords: Check point inhibitors; Immunotherapy; Multiple myeloma. © The Author(s), 2024. PubMed Disclaimer Similar articles Immune checkpoints and cancer immunotherapies: insights into newly potential receptors and ligands. Kamali AN, Bautista JM, Eisenhut M, Hamedifar H. Ther Adv Vaccines Immunother. 2023 Aug 30;11:25151355231192043. doi: 10.1177/25151355231192043. eCollection 2023. PMID: 37662491 Free PMC article. Review. Role of Next Generation Immune Checkpoint Inhibitor (ICI) Therapy in Philadelphia Negative Classic Myeloproliferative Neoplasm (MPN): Review of the Literature. Yadav R, Hakobyan N, Wang JC. Int J Mol Sci. 2023 Aug 7;24(15):12502. doi: 10.3390/ijms241512502. PMID: 37569880 Free PMC article. Review. The introduction of LAG-3 checkpoint blockade in melanoma: immunotherapy landscape beyond PD-1 and CTLA-4 inhibition. Kreidieh FY, Tawbi HA. Ther Adv Med Oncol. 2023 Jul 17;15:17588359231186027. doi: 10.1177/17588359231186027. eCollection 2023. PMID: 37484526 Free PMC article. Review. Role of Immunotherapy in Targeting the Bone Marrow Microenvironment in Multiple Myeloma: An Evolving Therapeutic Strategy. Chung C. Pharmacotherapy. 2017 Jan;37(1):129-143. doi: 10.1002/phar.1871. Epub 2017 Jan 6. PMID: 27870103 Review. Immune checkpoint inhibitors: breakthroughs in cancer treatment. Kong X, Zhang J, Chen S, Wang X, Xi Q, Shen H, Zhang R. Cancer Biol Med. 2024 May 24;21(6):451-72. doi: 10.20892/j.issn.2095-3941.2024.0055. PMID: 38801082 Free PMC article. Review. See all similar articles References Kumar SK, Rajkumar V, Kyle RA, et al.. Multiple myeloma. Nat Rev Dis Primers 2017; 3: 17046. - PubMed Romano A, Conticello C, Cavalli, et al.. Immunological dysregulation in multiple myeloma microenvironment. Biomed Res Int 2014; 2014: 198539. - PMC - PubMed Pratt G, Goodyear O, Moss P. Immunodeficiency and immunotherapy in multiple myeloma. Br J Haematol 2007; 138(5): 563–579. - PubMed Brocke-Heidrich K, Kretzschmar AK, Pfeifer G, et al.. Interleukin-6-dependent gene expression profiles in multiple myeloma INA-6 cells reveal a Bcl-2 family-independent survival pathway closely associated with Stat3 activation. Blood 2004; 103(1): 242–251. - PubMed Gu J, Huang X, Zhang Y, et al.. Cytokine profiles in patients with newly diagnosed multiple myeloma: survival is associated with IL-6 and IL-17A levels. Cytokine 2021; 138: 155358. - PubMed Show all 90 references Publication types Review Related information MedGen LinkOut - more resources Full Text Sources Atypon PubMed Central Research Materials NCI CPTC Antibody Characterization Program

Citation

Kamali AN, Hamedifar H, Eisenhut M, Bautista JM. Multiple myeloma and the potential of new checkpoint inhibitors for immunotherapy. Ther Adv Vaccines Immunother. 2024 Oct 9;12:25151355241288453. doi: 10.1177/25151355241288453. PMID: 39399301; PMCID: PMC11467827.