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      Management of belantamab mafodotin-associated corneal events in patients with relapsed or refractory multiple myeloma (RRMM)

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          Abstract

          Belantamab mafodotin (belamaf) demonstrated deep and durable responses in patients with heavily pretreated relapsed or refractory multiple myeloma (RRMM) in DREAMM-2 (NCT03525678). Corneal events, specifically keratopathy (including superficial punctate keratopathy and/or microcyst-like epithelial changes (MECs), eye examination findings with/without symptoms), were common, consistent with reports from other antibody–drug conjugates. Given the novel nature of corneal events in RRMM management, guidelines are required for their prompt identification and appropriate management. Eye examination findings from DREAMM-2 and insights from hematology/oncology investigators and ophthalmologists, including corneal specialists, were collated and used to develop corneal event management guidelines. The following recommendations were formulated: close collaboration among hematologist/oncologists and eye care professionals is needed, in part, to provide optimal care in relation to the belamaf benefit–risk profile. Patients receiving belamaf should undergo eye examinations before and during every treatment cycle and promptly upon worsening of symptoms. Severity of corneal events should be determined based on corneal examination findings and changes in best-corrected visual acuity. Treatment decisions, including dose modifications, should be based on the most severe finding present. These guidelines are recommended for the assessment and management of belamaf-associated ocular events to help mitigate ocular risk and enable patients to continue to experience a clinical benefit with belamaf.

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          Most cited references33

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          Belantamab mafodotin for relapsed or refractory multiple myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study

          Belantamab mafodotin (GSK2857916), an immunoconjugate targeting B-cell maturation antigen, showed single-agent activity in the phase 1 DREAMM-1 study in heavily pre-treated patients with relapsed or refractory multiple myeloma. We further investigated the safety and activity of belantamab mafodotin in the DREAMM-2 study.
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            Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy

            The introduction of CD38-targeting monoclonal antibodies (CD38 MoABs), daratumumab and isatuximab, has significantly impacted the management of patients with multiple myeloma (MM). Outcomes of patients with MM refractory to CD38 MoABs have not been described. We analyzed outcomes of 275 MM patients at 14 academic centers with disease refractory to CD38 MoABs. Median interval between MM diagnosis and refractoriness to CD38 MoAB (T 0 ) was 50.1 months. The median overall survival (OS) from T 0 for the entire cohort was 8.6 [95% C.I. 7.5–9.9] months, ranging from 11.2 months for patients not simultaneously refractory to an immunomodulatory (IMiD) agent and a proteasome inhibitor (PI) to 5.6 months for “penta-refractory” patients (refractory to CD38 MoAB, 2 PIs and 2 IMiDs). At least one subsequent treatment regimen was employed after T 0 in 249 (90%) patients. Overall response rate to first regimen after T 0 was 31% with median progression-free survival (PFS) and OS of 3.4 and 9.3 months, respectively. PFS was best achieved with combinations of carfilzomib and alkylator (median 5.7 months), and daratumumab and IMiD (median 4.5 months). Patients with MM refractory to CD38 MoAB have poor prognosis and this study provides benchmark for new therapies to be tested in this population.
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              Oral Selinexor–Dexamethasone for Triple-Class Refractory Multiple Myeloma

              Selinexor, a selective inhibitor of nuclear export compound that blocks exportin 1 (XPO1) and forces nuclear accumulation and activation of tumor suppressor proteins, inhibits nuclear factor κB, and reduces oncoprotein messenger RNA translation, is a potential novel treatment for myeloma that is refractory to current therapeutic options.
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                Author and article information

                Contributors
                sloni01@emory.edu
                Journal
                Blood Cancer J
                Blood Cancer J
                Blood Cancer Journal
                Nature Publishing Group UK (London )
                2044-5385
                26 May 2021
                26 May 2021
                May 2021
                : 11
                : 5
                : 103
                Affiliations
                [1 ]GRID grid.189967.8, ISNI 0000 0001 0941 6502, Emory University, Winship Cancer Institute, ; Atlanta, GA USA
                [2 ]GRID grid.418814.0, ISNI 0000 0004 0613 718X, Emory Eye Center, Emory University, ; Atlanta, GA USA
                [3 ]GRID grid.411024.2, ISNI 0000 0001 2175 4264, University of Maryland School of Medicine, ; Baltimore, MD USA
                [4 ]GRID grid.411024.2, ISNI 0000 0001 2175 4264, Department of Ophthalmology and Visual Sciences, , University of Maryland School of Medicine, ; Baltimore, MD USA
                [5 ]GRID grid.412647.2, ISNI 0000 0000 9209 0955, University of Wisconsin, Carbone Cancer Center, ; Madison, WI USA
                [6 ]GRID grid.28803.31, ISNI 0000 0001 0701 8607, University of Wisconsin, ; Madison, WI USA
                [7 ]GRID grid.223827.e, ISNI 0000 0001 2193 0096, Huntsman Cancer Institute, , University of Utah, ; Salt Lake City, UT USA
                [8 ]GRID grid.223827.e, ISNI 0000 0001 2193 0096, Moran Eye Center, , University of Utah, ; Salt Lake City, UT USA
                [9 ]GRID grid.52996.31, ISNI 0000 0000 8937 2257, University College London Hospitals, NHS Foundation Trust, ; London, UK
                [10 ]GRID grid.451056.3, ISNI 0000 0001 2116 3923, NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, ; London, UK
                [11 ]GRID grid.418019.5, ISNI 0000 0004 0393 4335, GlaxoSmithKline, ; Upper Providence, PA USA
                [12 ]GRID grid.38142.3c, ISNI 000000041936754X, Massachusetts Eye and Ear, Harvard Medical School, ; Boston, MA USA
                [13 ]GRID grid.412578.d, ISNI 0000 0000 8736 9513, University of Chicago Medical Center, ; Chicago, IL USA
                [14 ]GRID grid.137628.9, ISNI 0000 0004 1936 8753, New York University Grossman School of Medicine, ; New York, NY USA
                Author information
                http://orcid.org/0000-0002-8322-9323
                http://orcid.org/0000-0003-4165-6869
                http://orcid.org/0000-0002-6975-1086
                http://orcid.org/0000-0002-2597-6822
                Article
                494
                10.1038/s41408-021-00494-4
                8155129
                34039952
                c4353d58-1c5d-4048-8ca0-694e127a67e5
                © The Author(s) 2021

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 23 December 2020
                : 31 March 2021
                : 26 April 2021
                Categories
                Article
                Custom metadata
                © The Author(s) 2021

                Oncology & Radiotherapy
                cancer,haematological cancer
                Oncology & Radiotherapy
                cancer, haematological cancer

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