Elotuzumab in the Treatment of Relapsed and Refractory Multiple Myeloma

Grosicki, Sebastian; Bednarczyk, Martyna; Barchnicka, Agnieszka; Grosicka, Olga

doi:10.2217/fon-2020-1088

Cited by 6 publications

(6 citation statements)

References 41 publications

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“…At the same time, SLAMF7 is thought to play a role In BM stromal interactions with MMPCs to promote survival and is also highly expressed by all stages of MMPCs [294,295]. The landmark advancement in MM therapy was the development and approval of the monoclonal antibodies elotuzumab (anti-SLAMF7) and daratumumab (anti-CD38) in 2015 for both monotherapy and combination forms, particularly in the case of RRMM [296][297][298][299][300][301]. The first anti-BCMA CAR-T cells were made by lentiviral vector-mediated transfection in 2013 using a single-chain variable fragment from mouse anti-BCMA antibody combined with hinge and transmembrane regions of human CD8α, CD3ζ T-cell activation domain, and a costimulatory molecule (CD28), and the first clinical trial took place in 2016 to show potent cytotoxicity in refractory MM [302,303].…”

Section: Immunotherapy In Multiple Myelomamentioning

confidence: 99%

Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma

Sharma,

Choudhary

2023

Biomolecules

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Multiple myeloma (MM) is a dyscrasia of plasma cells (PCs) characterized by abnormal immunoglobulin (Ig) production. The disease remains incurable due to a multitude of mutations and structural abnormalities in MM cells, coupled with a favorable microenvironment and immune suppression that eventually contribute to the development of drug resistance. The bone marrow microenvironment (BMME) is composed of a cellular component comprising stromal cells, endothelial cells, osteoclasts, osteoblasts, and immune cells, and a non-cellular component made of the extracellular matrix (ECM) and the liquid milieu, which contains cytokines, growth factors, and chemokines. The bone marrow stromal cells (BMSCs) are involved in the adhesion of MM cells, promote the growth, proliferation, invasion, and drug resistance of MM cells, and are also crucial in angiogenesis and the formation of lytic bone lesions. Classical immunophenotyping in combination with advanced immune profiling using single-cell sequencing technologies has enabled immune cell-specific gene expression analysis in MM to further elucidate the roles of specific immune cell fractions from peripheral blood and bone marrow (BM) in myelomagenesis and progression, immune evasion and exhaustion mechanisms, and development of drug resistance and relapse. The review describes the role of BMME components in MM development and ongoing clinical trials using immunotherapeutic approaches.

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Section: Immunotherapy In Multiple Myelomamentioning

confidence: 99%

Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma

Sharma,

Choudhary

2023

Biomolecules

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“…Lenalidomide and pomalidomide are used in combination with dexamethasone for treating multiple myeloma. The anti-SLAMF7 monoclonal antibody elotuzumab, which was associated with safety signals for lens disorders, is also used with lenalidomide/dexamethasone for multiple myeloma (34). These drugs may cause cataract and other lens disorders.…”

Section: Ic Equationsmentioning

confidence: 99%

Analyses of Ocular Adverse Reactions Associated With Anticancer Drugs Based on the Japanese Pharmacovigilance Database

et al. 2022

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Background/Aim: The systemic administration of anticancer drugs may cause ocular adverse reactions (OARs). However, such adverse events are generally rare and occur with an unknown frequency. This study aimed to investigate the tendency of occurrence of OARs induced by systemic anticancer drugs using a large spontaneous pharmacovigilance database in Japan. Patients and Methods: The safety signals for eight OARs (periorbital and eyelid, conjunctival, corneal, scleral, lacrimal, lens, retinal, and optic nerve disorders) and their associations with anticancer drugs were evaluated by analyzing reporting odds ratios (RORs) and information components (ICs) based on data from the Japanese Adverse Drug Event Report (JADER). Results: Safety signals associated with anticancer drugs were detected for periorbital and eyelid disorders (imatinib), conjunctival disorders (imatinib and lapatinib), corneal disorders (S-1, erlotinib, capecitabine, cetuximab, gefitinib, vandetanib, trastuzumab emtansine, lapatinib), lacrimal disorders (S-1, pembrolizumab), lens disorders (lenalidomide, pomalidomide, elotuzumab, tamoxifen, bexarotene, venetoclax), retinal disorders (encorafenib, binimetinib, tamoxifen, nabpaclitaxel, trametinib, dabrafenib), and optic nerve disorders (tamoxifen and blinatumomab). Some anticancer drugs showed differences in safety signals based on sex and age. Conclusion: Safety signals indicative of the risk of occurrence of OARs were observed for several anticancer drugs, and several hitherto unreported ocular adverse events requiring caution were also detected. Our results will help predict the occurrence of OARs by oncologists, ophthalmologists, pharmacists, and other healthcare professionals.

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“…CD138 (syndecan-1) was the target of a CAR construct on NK-92 cells that were found to be more effective against MM xenografts than NK92 cells without this modification [ 140 ]. CS1 (CD319, CRACC, SLAMF7), the target for Elotuzumab [ 141 ], has also shown promise as a CAR-NK target in preclinical models [ 142 ]. An NKG2D-CAR is hoped to be effective for late-stage disease, which, through immunoediting, may no longer express classical antigens and thus, be capable of broad escape [ 143 ].…”

Section: Targeting Innate Lymphoid Cells For Multiple Myeloma Immunotherapymentioning

confidence: 99%

Therapeutic Potential of Innate Lymphoid Cells for Multiple Myeloma Therapy

Szudy‐Szczyrek

Ahern

Kozioł

et al. 2021

Cancers

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Innate lymphoid cells (ILCs) are a recently identified family of lymphocyte-like cells lacking a specific antigen receptor. They are part of the innate immune system. They play a key role in tissue homeostasis and also control inflammatory and neoplastic processes. In response to environmental stimuli, ILCs change their phenotype and functions, and influence the activity of other cells in the microenvironment. ILC dysfunction can lead to a wide variety of diseases, including cancer. ILC can be divided into three subgroups: ILC Group 1, comprising NK cells and ILC1; Group 2, including ILC2 alone; and Group 3, containing Lymphoid Tissue inducers (LTi) and ILC3 cells. While Group 1 ILCs mainly exert antitumour activity, Group 2 and Group 3 ILCs are protumorigenic in nature. A growing body of preclinical and clinical data support the role of ILCs in the pathogenesis of multiple myeloma (MM). Therefore, targeting ILCs may be of clinical benefit. In this manuscript, we review the available data on the role of ILCs in MM immunology and therapy.

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Elotuzumab in the Treatment of Relapsed and Refractory Multiple Myeloma

Cited by 6 publications

References 41 publications

Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma

Good Cop, Bad Cop: Profiling the Immune Landscape in Multiple Myeloma

Analyses of Ocular Adverse Reactions Associated With Anticancer Drugs Based on the Japanese Pharmacovigilance Database

Therapeutic Potential of Innate Lymphoid Cells for Multiple Myeloma Therapy

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