Isatuximab: A Review of Its Use in Multiple Myeloma

Frampton, James E.

doi:10.1007/s11523-021-00827-0

Cited by 23 publications

(19 citation statements)

References 52 publications

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“…Monoclonal antibodies (mAbs) exert their cytotoxic function through different mechanisms: antibody-dependent cellular cytotoxicity (ADCC) through the engagement of immune effector cells, complement activation, antibody-dependent phagocytosis, and direct effects on target cells acting through different signaling pathways. Several mAbs are currently approved for the treatment of MM: elotuzumab, an IgG1κ mAb with a specificity against SLAMF7, daratumumab and isatuximab, humanizeds IgG1 mAb that targets CD38 [ 125 , 126 ]. Resistance to daratumumab is probably associated with an alteration in the CDC mechanism mediated by the overexpression of the complement inhibitory proteins CD55 and CD59 [ 97 , 126 ].…”

Section: Roles Of Cytokines In Drug Resistance In Multiple Myelomamentioning

confidence: 99%

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

Melaccio

Reale

Saltarella

et al. 2022

JCM

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Multiple myeloma (MM) is the second most common hematological malignancy, and despite the introduction of innovative therapies, remains an incurable disease. Identifying early and minimally or non-invasive biomarkers for predicting clinical outcomes and therapeutic responses is an active field of investigation. Malignant plasma cells (PCs) reside in the bone marrow (BM) microenvironment (BMME) which comprises cells (e.g., tumour, immune, stromal cells), components of the extracellular matrix (ECM) and vesicular and non-vesicular (soluble) molecules, all factors that support PCs’ survival and proliferation. The interaction between PCs and BM stromal cells (BMSCs), a hallmark of MM progression, is based not only on intercellular interactions but also on autocrine and paracrine circuits mediated by soluble or vesicular components. In fact, PCs and BMSCs secrete various cytokines, including angiogenic cytokines, essential for the formation of specialized niches called “osteoblastic and vascular niches”, thus supporting neovascularization and bone disease, vital processes that modulate the pathophysiological PCs–BMME interactions, and ultimately promoting disease progression. Here, we aim to discuss the roles of cytokines and growth factors in pathogenetic pathways in MM and as prognostic and predictive biomarkers. We also discuss the potential of targeted drugs that simultaneously block PCs’ proliferation and survival, PCs–BMSCs interactions and BMSCs activity, which may represent the future goal of MM therapy.

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Section: Roles Of Cytokines In Drug Resistance In Multiple Myelomamentioning

confidence: 99%

Pathways of Angiogenic and Inflammatory Cytokines in Multiple Myeloma: Role in Plasma Cell Clonal Expansion and Drug Resistance

Melaccio

Reale

Saltarella

et al. 2022

JCM

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“…It was granted accelerated approval for marketing as treatment drug by the U.S. FDA in 2020 [ 59 ]. Isatuximab (Sarclisa®) is an anti-CD38 mAb [ 60 ] for use in the treatment of adults with multiple myeloma (MM) [ 61 , 62 ].…”

Section: Monoclonal Antibodies (Mabs)mentioning

confidence: 99%

Development of therapeutic antibodies for the treatment of diseases

Wang

et al. 2022

Mol Biomed

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Since the first monoclonal antibody drug, muromonab-CD3, was approved for marketing in 1986, 165 antibody drugs have been approved or are under regulatory review worldwide. With the approval of new drugs for treating a wide range of diseases, including cancer and autoimmune and metabolic disorders, the therapeutic antibody drug market has experienced explosive growth. Monoclonal antibodies have been sought after by many biopharmaceutical companies and scientific research institutes due to their high specificity, strong targeting abilities, low toxicity, side effects, and high development success rate. The related industries and markets are growing rapidly, and therapeutic antibodies are one of the most important research and development areas in the field of biology and medicine. In recent years, great progress has been made in the key technologies and theoretical innovations provided by therapeutic antibodies, including antibody–drug conjugates, antibody-conjugated nuclides, bispecific antibodies, nanobodies, and other antibody analogs. Additionally, therapeutic antibodies can be combined with technologies used in other fields to create new cross-fields, such as chimeric antigen receptor T cells (CAR-T), CAR-natural killer cells (CAR-NK), and other cell therapy. This review summarizes the latest approved or in regulatory review therapeutic antibodies that have been approved or that are under regulatory review worldwide, as well as clinical research on these approaches and their development, and outlines antibody discovery strategies that have emerged during the development of therapeutic antibodies, such as hybridoma technology, phage display, preparation of fully human antibody from transgenic mice, single B-cell antibody technology, and artificial intelligence-assisted antibody discovery.

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“…Based on two phase III clinical trials, the FDA has recently approved isatuximab in combination with dexamethasone and pomalidomide/carfilzomib in 2020 and 2021, respectively, for patients with RRMM that have previously received specific treatments ( Attal et al., 2019 ; Shah and Mailankody, 2020 ; Frampton, 2021 ; Moreau et al., 2021 ; Clinical Trials, 2022 ).…”

Section: Immunotherapy Strategies For Hematological Cancer Treatmentmentioning

confidence: 99%