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      The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of multiple myeloma

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          Abstract

          Outcomes in multiple myeloma (MM) have improved dramatically in the last two decades with the advent of novel therapies including immunomodulatory agents (IMiDs), proteasome inhibitors and monoclonal antibodies. In recent years, immunotherapy for the treatment of MM has advanced rapidly, with the approval of new targeted agents and monoclonal antibodies directed against myeloma cell-surface antigens, as well as maturing data from late stage trials of chimeric antigen receptor CAR T cells. Therapies that engage the immune system to treat myeloma offer significant clinical benefits with durable responses and manageable toxicity profiles, however, the appropriate use of these immunotherapy agents can present unique challenges for practicing physicians. Therefore, the Society for Immunotherapy of Cancer convened an expert panel, which met to consider the current role of approved and emerging immunotherapy agents in MM and provide guidance to the oncology community by developing consensus recommendations. As immunotherapy evolves as a therapeutic option for the treatment of MM, these guidelines will be updated.

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          Most cited references143

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          Early and late hematologic toxicity following CD19 CAR-T cells

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            γ-secretase directly sheds the survival receptor BCMA from plasma cells

            Survival of plasma cells is regulated by B-cell maturation antigen (BCMA), a membrane-bound receptor activated by its agonist ligands BAFF and APRIL. Here we report that γ-secretase directly cleaves BCMA, without prior truncation by another protease. This direct shedding is facilitated by the short length of BCMA's extracellular domain. In vitro, γ-secretase reduces BCMA-mediated NF-κB activation. In addition, γ-secretase releases soluble BCMA (sBCMA) that acts as a decoy neutralizing APRIL. In vivo, inhibition of γ-secretase enhances BCMA surface expression in plasma cells and increases their number in the bone marrow. Furthermore, in multiple sclerosis, sBCMA levels in spinal fluid are elevated and associated with intracerebral IgG production; in systemic lupus erythematosus, sBCMA levels in serum are elevated and correlate with disease activity. Together, shedding of BCMA by γ-secretase controls plasma cells in the bone marrow and yields a potential biomarker for B-cell involvement in human autoimmune diseases.
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              FDA Approval: Blinatumomab.

              On December 3, 2014, the FDA granted accelerated approval of blinatumomab (Blincyto; Amgen, Inc.) for treatment of Philadelphia chromosome-negative relapsed or refractory precursor B-cell acute lymphoblastic leukemia (R/R ALL). Blinatumomab is a recombinant murine protein that acts as a bispecific CD19-directed CD3 T-cell engager. The basis for the approval was a single-arm trial with 185 evaluable adults with R/R ALL. The complete remission (CR) rate was 32% [95% confidence interval (CI), 26%-40%], and the median duration of response was 6.7 months. A minimal residual disease response was achieved by 31% (95% CI, 25%-39%) of all patients. Cytokine release syndrome and neurologic events were serious toxicities that occurred. Other common (>20%) adverse reactions were pyrexia, headache, edema, febrile neutropenia, nausea, tremor, and rash. Neutropenia, thrombocytopenia, and elevated transaminases were the most common (>10%) laboratory abnormalities related to blinatumomab. A randomized trial is required in order to confirm clinical benefit.
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                Author and article information

                Journal
                J Immunother Cancer
                J Immunother Cancer
                jitc
                jitc
                Journal for Immunotherapy of Cancer
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2051-1426
                2020
                12 July 2020
                : 8
                : 2
                : e000734
                Affiliations
                [1 ] departmentDivision of Hematology-Oncology, Department of Medicine , University of California San Francisco , San Francisco, California, USA
                [2 ] Patient Empowerment Network , San Jose, California, USA
                [3 ] departmentDivision of Hematology and Hematologic Malignancies , Beth Israel Deaconess Medical Center , Boston, Massachusetts, USA
                [4 ] departmentDepartment of Medicine , Sarah Cannon Research Institute , Nashville, Tennessee, USA
                [5 ] departmentDepartment of Oncology , The Sidney Kimmel Comprehensive Cancer Center of Johns Hopkins , Baltimore, Maryland, USA
                [6 ] departmentHematology and Medical Oncology , Icahn School of Medicine at Mount Sinai , New York, New York, USA
                [7 ] departmentDepartment of Medicine , Abramson Cancer Center at the University of Pennsylvania , Philadelphia, Pennsylvania, USA
                [8 ] departmentDepartment of Laboratory Medicine , University of California San Francisco , San Francisco, California, USA
                [9 ] University of California San Francisco , San Francisco, CA, USA
                [10 ] departmentClinical Research Division , Fred Hutchinson Cancer Research Center , Seattle, Washington, USA
                [11 ] departmentDepartment of Hematology and Hematopoietic Cell Transplantation , Judy and Bernard Briskin Multiple Myeloma Center for Clinical Research, City of Hope Comprehensive Cancer Center , Duarte, California, USA
                [12 ] departmentDivision of Hematology, Department of Internal Medicine , Mayo Clinic , Rochester, Minnesota, USA
                [13 ] departmentDivision of Experimental Pathology, Department of Laboratory Medicine and Pathology , Mayo Clinic , Rochester, Minnesota, USA
                [14 ] departmentDepartment of Lymphoma/Myeloma , The University of Texas MD Anderson Cancer Center , Houston, Texas, USA
                [15 ] departmentJerome Lipper Multiple Myeloma Disease Center , Dana-Farber Cancer Institute, Harvard Medical School , Boston, Massachusetts, USA
                [16 ] departmentDepartment of Hematology/Oncology , Emory University , Atlanta, Georgia, USA
                [17 ] University of Maryland Greenebaum Comprehensive Cancer Center , Baltimore, Maryland, USA
                [18 ] departmentMyeloma Service and Cellular Therapeutics Center, Department of Medicine , Memorial Sloan Kettering Cancer Center , New York, New York, USA
                [19 ] departmentDivision of Medical Oncology, Siteman Cancer Center , Washington University in Saint Louis School of Medicine , Saint Louis, Missouri, USA
                [20 ] departmentSchool of Medicine, Department of Hematology and Medical Oncology, Winship Cancer Institute , Emory University , Atlanta, Georgia, USA
                Author notes
                [Correspondence to ] Dr Madhav Dhodapkar; madhav.v.dhodapkar@ 123456emory.edu
                Article
                jitc-2020-000734
                10.1136/jitc-2020-000734
                7359060
                32661116
                5999abe2-4f99-409e-8628-26472d522af8
                © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 01 June 2020
                Categories
                Position Article and Guidelines
                1506
                2446
                Custom metadata
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                guidelines as topic,immunotherapy,hematological neoplasms,receptors, chimeric antigen,antineoplastic protocols

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