Literature DB >> 27493709

Elotuzumab: the first approved monoclonal antibody for multiple myeloma treatment.

Hila Magen1, Eli Muchtar2.   

Abstract

Elotuzumab is a monoclonal antibody directed against the SLAMF7 receptor, expressed on normal and malignant plasma cells with a lower expression on other lymphoid cells such as natural killer (NK) cells. Elotuzumab has no significant antimyeloma activity when given as a single agent to patients with relapsed or refractory multiple myeloma (RRMM). However, when combined with other antimyeloma agents, it results in improved response and outcome. Owing to the results from the landmark ELOQUENT-2 phase III clinical trial, which compared lenalidomide and dexamethasone with or without elotuzumab in patients with RRMM, elotuzumab in combination with lenalidomide and dexamethasone was approved by the American Food and Drug Administration (FDA) in November 2015 for multiple myeloma (MM) patients who received one to three prior lines of therapy. This review will give a brief description of the signaling lymphocytic activation molecule (SLAM) family receptors, the unique SLAMF7 receptor and the mechanism of action of elotuzumab. Thereafter, we will give an overview on its antimyeloma activity in preclinical and clinical trials, including its toxicity profile and management thereof.

Entities:  

Keywords:  combined therapy; elotuzumab; immunomodulatory drugs; multiple myeloma; proteasome inhibitors; relapse

Year:  2016        PMID: 27493709      PMCID: PMC4959642          DOI: 10.1177/2040620716652862

Source DB:  PubMed          Journal:  Ther Adv Hematol        ISSN: 2040-6207


  28 in total

1.  Elotuzumab in combination with lenalidomide and dexamethasone in patients with relapsed multiple myeloma: final phase 2 results from the randomised, open-label, phase 1b-2 dose-escalation study.

Authors:  Paul G Richardson; Sundar Jagannath; Philippe Moreau; Andrzej J Jakubowiak; Marc S Raab; Thierry Facon; Ravi Vij; Darrell White; Donna E Reece; Lotfi Benboubker; Jeffrey Zonder; L Claire Tsao; Kenneth C Anderson; Eric Bleickardt; Anil K Singhal; Sagar Lonial
Journal:  Lancet Haematol       Date:  2015-11-16       Impact factor: 18.959

2.  Influence of CRACC, a SLAM family receptor coupled to the adaptor EAT-2, on natural killer cell function.

Authors:  Mario-Ernesto Cruz-Munoz; Zhongjun Dong; Xiaochu Shi; Shaohua Zhang; André Veillette
Journal:  Nat Immunol       Date:  2009-01-18       Impact factor: 25.606

3.  Negative regulation of natural killer cell function by EAT-2, a SAP-related adaptor.

Authors:  Romain Roncagalli; James E R Taylor; Shaohua Zhang; Xiaochu Shi; Riyan Chen; Mario-Ernesto Cruz-Munoz; Luo Yin; Sylvain Latour; André Veillette
Journal:  Nat Immunol       Date:  2005-08-28       Impact factor: 25.606

Review 4.  CS1, a SLAM family receptor involved in immune regulation, is a therapeutic target in multiple myeloma.

Authors:  André Veillette; Huaijian Guo
Journal:  Crit Rev Oncol Hematol       Date:  2013-06-02       Impact factor: 6.312

5.  Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu.

Authors:  Yu-Tzu Tai; Myles Dillon; Weihua Song; Merav Leiba; Xian-Feng Li; Peter Burger; Alfred I Lee; Klaus Podar; Teru Hideshima; Audie G Rice; Anne van Abbema; Lynne Jesaitis; Ingrid Caras; Debbie Law; Edie Weller; Wanling Xie; Paul Richardson; Nikhil C Munshi; Claire Mathiot; Hervé Avet-Loiseau; Daniel E H Afar; Kenneth C Anderson
Journal:  Blood       Date:  2007-09-28       Impact factor: 22.113

6.  Inhibition and activation by CD244 depends on CD2 and phospholipase C-gamma1.

Authors:  Nicholas G Clarkson; Marion H Brown
Journal:  J Biol Chem       Date:  2009-07-08       Impact factor: 5.157

7.  Combinatorial efficacy of anti-CS1 monoclonal antibody elotuzumab (HuLuc63) and bortezomib against multiple myeloma.

Authors:  Frits van Rhee; Susann M Szmania; Myles Dillon; Anne M van Abbema; Xin Li; Mary K Stone; Tarun K Garg; JuMei Shi; Amberly M Moreno-Bost; Rui Yun; Balaji Balasa; Bishwa Ganguly; Debra Chao; Audie G Rice; Fenghuang Zhan; John D Shaughnessy; Bart Barlogie; Shmuel Yaccoby; Daniel E H Afar
Journal:  Mol Cancer Ther       Date:  2009-09-01       Impact factor: 6.261

8.  Profile of elotuzumab and its potential in the treatment of multiple myeloma.

Authors:  Yi-Chang Liu; Susann Szmania; Frits van Rhee
Journal:  Blood Lymphat Cancer       Date:  2014-06

9.  EAT-2, a SAP-like adaptor, controls NK cell activation through phospholipase Cγ, Ca++, and Erk, leading to granule polarization.

Authors:  Luis-Alberto Pérez-Quintero; Romain Roncagalli; Huaijian Guo; Sylvain Latour; Dominique Davidson; André Veillette
Journal:  J Exp Med       Date:  2014-03-31       Impact factor: 14.307

10.  Elotuzumab enhances natural killer cell activation and myeloma cell killing through interleukin-2 and TNF-α pathways.

Authors:  Balaji Balasa; Rui Yun; Nicole A Belmar; Melvin Fox; Debra T Chao; Michael D Robbins; Gary C Starling; Audie G Rice
Journal:  Cancer Immunol Immunother       Date:  2014-10-07       Impact factor: 6.968

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Authors:  Antonia Rotolo; Anastasios Karadimitris; Marco Ruella
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Review 3.  Infectious Complications of Biological and Small Molecule Targeted Immunomodulatory Therapies.

Authors:  Joshua S Davis; David Ferreira; Emma Paige; Craig Gedye; Michael Boyle
Journal:  Clin Microbiol Rev       Date:  2020-06-10       Impact factor: 26.132

Review 4.  Practical guidance for new multiple myeloma treatment regimens: A nursing perspective.

Authors:  Monica Epstein; Candis Morrison
Journal:  Semin Oncol       Date:  2022-02-10       Impact factor: 5.385

5.  Elotuzumab, a potential therapeutic humanized anti-SLAMF7 monoclonal antibody, enhances natural killer cell-mediated killing of primary effusion lymphoma cells.

Authors:  Jutatip Panaampon; Ryusho Kariya; Seiji Okada
Journal:  Cancer Immunol Immunother       Date:  2022-03-09       Impact factor: 6.630

Review 6.  Recombinant Antibodies to Arm Cytotoxic Lymphocytes in Cancer Immunotherapy.

Authors:  Joachim Koch; Michael Tesar
Journal:  Transfus Med Hemother       Date:  2017-09-11       Impact factor: 3.747

Review 7.  Chimeric Antigen Receptor T Cells for Multiple Myeloma: The Journey So Far-And the Road Ahead.

Authors:  Andrew J Cowan; Sherilyn A Tuazon; Andrew J Portuguese; Damian J Green
Journal:  Cancer J       Date:  2021 Mar-Apr 01       Impact factor: 2.074

Review 8.  New Strategies Using Antibody Combinations to Increase Cancer Treatment Effectiveness.

Authors:  Isabel Corraliza-Gorjón; Beatriz Somovilla-Crespo; Silvia Santamaria; Jose A Garcia-Sanz; Leonor Kremer
Journal:  Front Immunol       Date:  2017-12-21       Impact factor: 7.561

Review 9.  Restoring Natural Killer Cell Immunity against Multiple Myeloma in the Era of New Drugs.

Authors:  Gianfranco Pittari; Luca Vago; Moreno Festuccia; Chiara Bonini; Deena Mudawi; Luisa Giaccone; Benedetto Bruno
Journal:  Front Immunol       Date:  2017-11-07       Impact factor: 7.561

Review 10.  The future of myeloma precision medicine: integrating the compendium of known drug resistance mechanisms with emerging tumor profiling technologies.

Authors:  Taylor Harding; Linda Baughn; Shaji Kumar; Brian Van Ness
Journal:  Leukemia       Date:  2019-01-25       Impact factor: 11.528

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