Emerging combination therapies for the management of multiple myeloma: the role of elotuzumab
Wei-Chih Chen,1 Abraham S Kanate,2,3 Michael Craig,2,3 William P Petros,1,3 Lori A Hazlehurst1–3 1Department of Pharmaceutical Sciences, School of Pharmacy, 2Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, 3West Virginia University Cancer Institute, M...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2017-07-01
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| Series: | Cancer Management and Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/emerging-combination-therapies-for-the-management-of-multiple-myeloma--peer-reviewed-article-CMAR |
| _version_ | 1818278292992557056 |
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| author | Chen WC Kanate AS Craig M Petros WP Hazlehurst LA |
| author_facet | Chen WC Kanate AS Craig M Petros WP Hazlehurst LA |
| author_sort | Chen WC |
| collection | DOAJ |
| description | Wei-Chih Chen,1 Abraham S Kanate,2,3 Michael Craig,2,3 William P Petros,1,3 Lori A Hazlehurst1–3 1Department of Pharmaceutical Sciences, School of Pharmacy, 2Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, 3West Virginia University Cancer Institute, Morgantown, WV, USA Abstract: Treatment options for patients with multiple myeloma (MM) have increased during the past decade. Despite the significant advances, challenges remain on which combination strategies will provide the optimal response for any given patient. Defining optimal combination strategies and corresponding companion diagnostics, that will guide clinical decisions are required to target relapsed or refractory multiple myeloma (RRMM) in order to improve disease progression, survival and quality of life for patients with MM. Elotuzumab is a humanized monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7), approved by the US Food and Drug Administration (FDA) in 2015 and the European Medicines Agency in 2016 for the treatment of MM. SLAMF7 is expressed in normal and malignant plasma cells and has lower expression on natural killer (NK) cells. Experimental evidence indicates that elotuzumab exhibits anti-myeloma activity through 1) antibody-dependent cell-mediated cytotoxicity, 2) enhancing NK cells cytotoxicity and 3) interfering with adhesion of MM cells to bone marrow stem cells (BMSCs). Although elotuzumab has no single agent activity in patients with RRMM who have received one to three prior therapies, the combination of elotuzumab with anti-myeloma agents, such as immunomodulatory drugs-lenalidomide, or proteasome inhibitors (PIs)-bortezomib, remarkably improved the overall response rates and progression-free survival in MM patients with only minimal incremental toxicity. In brief, the clinical data for elotuzumab indicate that targeting SLAMF7 in combination with the use of conventional therapies is feasible and effective with a tolerable safety profile for the treatment of RRMM. Keywords: elotuzumab, SLAMF7, relapsed/refractory multiple myeloma (RRMM) |
| first_indexed | 2024-12-12T23:15:08Z |
| format | Article |
| id | doaj.art-6cd06de8f02243ba905f444029e8ff5f |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-12T23:15:08Z |
| publishDate | 2017-07-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-6cd06de8f02243ba905f444029e8ff5f2022-12-22T00:08:28ZengDove Medical PressCancer Management and Research1179-13222017-07-01Volume 930731433719Emerging combination therapies for the management of multiple myeloma: the role of elotuzumabChen WCKanate ASCraig MPetros WPHazlehurst LAWei-Chih Chen,1 Abraham S Kanate,2,3 Michael Craig,2,3 William P Petros,1,3 Lori A Hazlehurst1–3 1Department of Pharmaceutical Sciences, School of Pharmacy, 2Osborn Hematopoietic Malignancy and Transplantation Program, West Virginia University, 3West Virginia University Cancer Institute, Morgantown, WV, USA Abstract: Treatment options for patients with multiple myeloma (MM) have increased during the past decade. Despite the significant advances, challenges remain on which combination strategies will provide the optimal response for any given patient. Defining optimal combination strategies and corresponding companion diagnostics, that will guide clinical decisions are required to target relapsed or refractory multiple myeloma (RRMM) in order to improve disease progression, survival and quality of life for patients with MM. Elotuzumab is a humanized monoclonal antibody that targets signaling lymphocytic activation molecule F7 (SLAMF7), approved by the US Food and Drug Administration (FDA) in 2015 and the European Medicines Agency in 2016 for the treatment of MM. SLAMF7 is expressed in normal and malignant plasma cells and has lower expression on natural killer (NK) cells. Experimental evidence indicates that elotuzumab exhibits anti-myeloma activity through 1) antibody-dependent cell-mediated cytotoxicity, 2) enhancing NK cells cytotoxicity and 3) interfering with adhesion of MM cells to bone marrow stem cells (BMSCs). Although elotuzumab has no single agent activity in patients with RRMM who have received one to three prior therapies, the combination of elotuzumab with anti-myeloma agents, such as immunomodulatory drugs-lenalidomide, or proteasome inhibitors (PIs)-bortezomib, remarkably improved the overall response rates and progression-free survival in MM patients with only minimal incremental toxicity. In brief, the clinical data for elotuzumab indicate that targeting SLAMF7 in combination with the use of conventional therapies is feasible and effective with a tolerable safety profile for the treatment of RRMM. Keywords: elotuzumab, SLAMF7, relapsed/refractory multiple myeloma (RRMM)https://www.dovepress.com/emerging-combination-therapies-for-the-management-of-multiple-myeloma--peer-reviewed-article-CMARelotuzumabSLAMF7relapsed/refractory multiple myeloma (RRMM) |
| spellingShingle | Chen WC Kanate AS Craig M Petros WP Hazlehurst LA Emerging combination therapies for the management of multiple myeloma: the role of elotuzumab Cancer Management and Research elotuzumab SLAMF7 relapsed/refractory multiple myeloma (RRMM) |
| title | Emerging combination therapies for the management of multiple myeloma: the role of elotuzumab |
| title_full | Emerging combination therapies for the management of multiple myeloma: the role of elotuzumab |
| title_fullStr | Emerging combination therapies for the management of multiple myeloma: the role of elotuzumab |
| title_full_unstemmed | Emerging combination therapies for the management of multiple myeloma: the role of elotuzumab |
| title_short | Emerging combination therapies for the management of multiple myeloma: the role of elotuzumab |
| title_sort | emerging combination therapies for the management of multiple myeloma the role of elotuzumab |
| topic | elotuzumab SLAMF7 relapsed/refractory multiple myeloma (RRMM) |
| url | https://www.dovepress.com/emerging-combination-therapies-for-the-management-of-multiple-myeloma--peer-reviewed-article-CMAR |
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