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      Elotuzumab in the treatment of relapsed and refractory multiple myeloma

      1 , 1 , 2 , 3
      Future Oncology
      Future Medicine Ltd

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          Abstract

          Multiple myeloma (MM) is still considered an incurable disease. However, drugs with different mechanisms of action that can improve the efficiency of treatment offer hope. Still, there are concerns about an unacceptable increase in toxicity with such regimens. The results of recently published clinical studies of elotuzumab in combination with lenalidomide/dexamethasone or pomalidomide/dexamethasone confirm previous hopes to improve the effect of that treatment. Humanized monoclonal antibodies aimed at SLAMF7 stimulate natural killer cells to fight against MM cells. Elotuzumab used in combination with lenalidomide/dexamethasone or with pomalidomide/dexamethasone is approved by the US FDA to treat patients with relapsed and/or refractory MM. The article is a summary of the recent knowledge about the possibility of using elotuzumab in the treatment of relapsed and/or refractory MM and shows its potential uses in the future.

          Abstract

          Lay abstract

          Multiple myeloma remains an incurable cancer. The essential concerns are the high relapse rate and the developing resistance to treatment. In recent years, an increase in life expectancy and quality of life has been observed thanks to the introduction of drugs with new mechanisms of action and their use in therapeutic combinations. Monoclonal antibodies, including elotuzumab, have played a major role. Its combination with lenalidomide or pomalidomide and dexamethasone resulted in a significant improvement in the effectiveness of the treatment and did not increase the toxicity of the therapy. The article discusses the current knowledge about this drug, focusing mainly on the possibility of using this drug in the therapeutic process and prospects for the future.

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          Most cited references40

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          Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma.

          Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy.
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            The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody.

            T-cell expression of programmed death receptor-1 (PD-1) down-regulates the immune response against malignancy by interacting with cognate ligands (eg, PD-L1) on tumor cells; however, little is known regarding PD-1 and natural killer (NK) cells. NK cells exert cytotoxicity against multiple myeloma (MM), an effect enhanced through novel therapies. We show that NK cells from MM patients express PD-1 whereas normal NK cells do not and confirm PD-L1 on primary MM cells. Engagement of PD-1 with PD-L1 should down-modulate the NK-cell versus MM effect. We demonstrate that CT-011, a novel anti-PD-1 antibody, enhances human NK-cell function against autologous, primary MM cells, seemingly through effects on NK-cell trafficking, immune complex formation with MM cells, and cytotoxicity specifically toward PD-L1(+) MM tumor cells but not normal cells. We show that lenalidomide down-regulates PD-L1 on primary MM cells and may augment CT-011's enhancement of NK-cell function against MM. We demonstrate a role for the PD-1/PD-L1 signaling axis in the NK-cell immune response against MM and a role for CT-011 in enhancing the NK-cell versus MM effect. A phase 2 clinical trial of CT-011 in combination with lenalidomide for patients with MM should be considered.
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              Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma

              The combination of bortezomib, melphalan, and prednisone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. Daratumumab has shown efficacy in combination with standard-of-care regimens in patients with relapsed or refractory multiple myeloma.
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                Author and article information

                Contributors
                (View ORCID Profile)
                Journal
                Future Oncology
                Future Oncology
                Future Medicine Ltd
                1479-6694
                1744-8301
                May 2021
                May 2021
                : 17
                : 13
                : 1581-1591
                Affiliations
                [1 ]Department of Hematology & Cancer Prevention, Chorzow, Faculty of Health Sciences, Bytom, Medical University of Silesia, 40-055 Katowice, Poland
                [2 ]Clinical Department of Hematology & Cancer Prevention, Municipal Hospital, 41-500 Chorzow, Poland
                [3 ]Institute of Economics, Finance & Management, Faculty of Management & Social Communication, Jagiellonian University, 31-007 Cracow, Poland
                Article
                10.2217/fon-2020-1088
                543c99c7-3b8f-4817-8281-a9890416925c
                © 2021
                History

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