BCMA in Multiple Myeloma-A Promising Key to Therapy

被引:37
作者
Kleber, Martina [1 ,2 ]
Ntanasis-Stathopoulos, Ioannis [3 ]
Terpos, Evangelos [3 ]
机构
[1] Univ Hosp Zurich, Div Internal Med, CH-8091 Zurich, Switzerland
[2] Univ Basel, Fac Med, CH-4031 Basel, Switzerland
[3] Natl & Kapodistrian Univ Athens, Sch Med, Dept Clin Therapeut, Athens 11528, Greece
关键词
BCMA; multiple myeloma; antibody; conjugated; BiTE; ADC; CAR T cell; immunotherapy; CELL MATURATION ANTIGEN; ANTIBODY-DRUG CONJUGATE; RECEPTOR T-CELLS; BONE-MARROW; BELANTAMAB MAFODOTIN; BISPECIFIC ANTIBODY; PREDICT OUTCOMES; SURVIVAL; APRIL; CYTOTOXICITY;
D O I
10.3390/jcm10184088
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Despite the discoveries of numerous agents including next generation proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies, multiple myeloma (MM) remains an incurable disease. The field of myeloma treatment in refractory or relapsed patients after standard therapy entered a new era due to the B-cell maturation antigen (BMCA) targeted approach. BCMA is a member of the tumor necrosis factor receptor family with high expression in mature B-lymphocytes and plasma cells. Given the understanding of BCMA mechanism of action in MM, BCMA plays a promising role as a therapeutic target. Several clinical trials are underway to evolve the current BCMA targeted treatment concept such as antibody-drug conjugates (ADCs), bispecific T cell engagers (BITEs) and chimeric antigen receptor (CAR) T cell therapy. Current results of representative BCMA trials may close the gap of the unmet clinical need to further improve the outcome of heavily pretreated MM patients with the potency to change the paradigm in newly diagnosed and refractory MM. This comprehensive review will give an update on various BMCA targeted treatment modalities (ADCs, BITEs, CAR T cell therapy) and its existing results on efficacy and safety from preclinical and clinical trials.
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页数:17
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共 94 条
  • [1] T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma
    Ali, Syed Abbas
    Shi, Victoria
    Maric, Irina
    Wang, Michael
    Stroncek, David F.
    Rose, Jeremy J.
    Brudno, Jennifer N.
    Stetler-Stevenson, Maryalice
    Feldman, Steven A.
    Hansen, Brenna G.
    Fellowes, Vicki S.
    Hakim, Frances T.
    Gress, Ronald E.
    Kochenderfer, James N.
    [J]. BLOOD, 2016, 128 (13) : 1688 - 1700
  • [2] Osteoclasts promote immune suppressive microenvironment in multiple myeloma: therapeutic implication
    An, Gang
    Acharya, Chirag
    Feng, Xiaoyan
    Wen, Kenneth
    Zhong, Mike
    Zhang, Li
    Munshi, Nikhil C.
    Qiu, Lugui
    Tai, Yu-Tzu
    Anderson, Kenneth C.
    [J]. BLOOD, 2016, 128 (12) : 1590 - 1603
  • [3] [Anonymous], 2016, Blood, DOI DOI 10.1182/BLOOD.V128.22.383.383
  • [4] Overexpression of G protein-coupled receptor 5D in the bone marrow is associated with poor prognosis in patients with multiple myeloma
    Atamaniuk, Johanna
    Gleiss, Andreas
    Porpaczy, Edit
    Kainz, Birgit
    Grunt, Thomas W.
    Raderer, Markus
    Hilgarth, Bernadette
    Drach, Johannes
    Ludwig, Heinz
    Gisslinger, Heinz
    Jaeger, Ulrich
    Gaiger, Alexander
    [J]. EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 2012, 42 (09) : 953 - 960
  • [5] Berdeja JG, 2020, J CLIN ONCOL, V38
  • [6] A new decade: novel immunotherapies on the horizon for relapsed/refractory multiple myeloma
    Braunstein, Marc
    Weltz, Jonathan
    Davies, Faith
    [J]. EXPERT REVIEW OF HEMATOLOGY, 2021, 14 (04) : 377 - 389
  • [7] Pre-clinical development of TNB-383B, a fully human T-cell engaging bispecific antibody targeting BCMA for the treatment of multiple myeloma.
    Buelow, Ben
    Choudry, Priya
    Clarke, Starlynn
    Dang, Kevin
    Davison, Laura
    Aldred, Shelley Force
    Harris, Katherine
    Pratap, Payal
    Pham, Duy
    Rangaswamy, Udaya
    Schellenberger, Ute
    Shah, Nina
    Trinklein, Nathan
    Ugamraj, Harshad
    Wiita, Arun
    Van Schooten, Wim
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (15)
  • [8] Development of a fully human T cell engaging bispecific antibody for the treatment of multiple myeloma.
    Buelow, Ben
    Pham, Duy
    Clarke, Starlynn
    Aldred, Shelley Force
    Dang, Kevin
    Pratap, Payal
    Ugamraj, Harshad
    Harris, Katherine
    Trinklein, Nathan
    Schellenberger, Ute
    Wiita, Arun
    Van Schooten, Wim
    Buelow, Ben
    [J]. JOURNAL OF CLINICAL ONCOLOGY, 2017, 35
  • [9] B-cell Maturation Antigen Is a Promising Target for Adoptive T-cell Therapy of Multiple Myeloma
    Carpenter, Robert O.
    Evbuomwan, Moses O.
    Pittaluga, Stefania
    Rose, Jeremy J.
    Raffeld, Mark
    Yang, Shicheng
    Gress, Ronald E.
    Hakim, Frances T.
    Kochenderfer, James N.
    [J]. CLINICAL CANCER RESEARCH, 2013, 19 (08) : 2048 - 2060
  • [10] Management of relapsed and refractory multiple myeloma: novel agents, antibodies, immunotherapies and beyond
    Chim, C. S.
    Kumar, S. K.
    Orlowski, R. Z.
    Cook, G.
    Richardson, P. G.
    Gertz, M. A.
    Giralt, S.
    Mateos, M. V.
    Leleu, X.
    Anderson, K. C.
    [J]. LEUKEMIA, 2018, 32 (02) : 252 - 262