CAR T-Cells in Multiple Myeloma Are Ready for Prime Time

被引:19
作者
Rodriguez-Otero, Paula [1 ]
Prosper, Felipe [1 ]
Alfonso, Ana [1 ]
Paiva, Bruno [1 ]
San Miguel, Jesus F. [1 ]
机构
[1] Clin Univ Navarra, Ctr Invest Med Aplicada Cima, CIBERONC, IDISNA, Pamplona 31008, Spain
关键词
relapse and refractory multiple myeloma; B-cell maturation antigen; chimeric antigen receptor T cell (CAR T-cell) therapy; immunotherapy; MATURATION ANTIGEN; RECEPTOR; THERAPY; TARGET; BCMA; SURVIVAL; MEMBER; CD19;
D O I
10.3390/jcm9113577
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The survival of patients with multiple myeloma (MM) has been dramatically improved in the last decade thanks to the incorporation of second-generation proteasome inhibitors (PI), immunomodulatory drugs (IMID), and, more recently, anti-CD38 monoclonal antibodies (MoAb). Nevertheless, still, a major proportion of MM patients will relapse, underscoring the need for new therapies in this disease. Moreover, survival in patients failing the current standard of care regimens (including PI, IMIDs, and anti-CD38 MoAb), which is now defined as triple-class refractory, remains dismal, and new drugs with different mechanism of action are needed. B-cell maturation antigen (BCMA)-targeted therapies and in particular chimeric antigen receptor T cell (CAR T-cell) treatment have emerged as promising platforms to overcome refractoriness to conventional drugs. In this manuscript, we review the current available data regarding CAR T-cell therapy for MM, with a special focus on target selection, clinical results, limitations, and future strategies.
引用
收藏
页码:1 / 16
页数:16
相关论文
共 48 条
[1]   Remissions of Multiple Myeloma during a First-in-Humans Clinical Trial of T Cells Expressing an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor [J].
Ali, Syed Abbas ;
Shi, Victoria ;
Wang, Michael ;
Stroncek, David ;
Maric, Irina ;
Brudno, Jennifer N. ;
Stetler-Stevenson, Maryalice ;
Rose, Jeremy J. ;
Feldman, Steven ;
Hansen, Brenna ;
Hakim, Frances T. ;
Gress, Ronald E. ;
Kochenderfer, James N. .
BLOOD, 2015, 126 (23)
[2]  
[Anonymous], 2019, BLOOD S1, DOI DOI 10.1182/blood-2019-126660
[3]   Phase I Trial of Autologous CAR T Cells Targeting NKG2D Ligands in Patients with AML/MDS and Multiple Myeloma [J].
Baumeister, Susanne H. ;
Murad, Joana ;
Werner, Lillian ;
Daley, Heather ;
Trebeden-Negre, Helene ;
Gicobi, Joanina K. ;
Schmucker, Adam ;
Reder, Jake ;
Sentman, Charles L. ;
Gilham, David E. ;
Lehmann, Frederic F. ;
Galinsky, Ilene ;
DiPietro, Heidi ;
Cummings, Kristen ;
Munshi, Nikhil C. ;
Stone, Richard M. ;
Neuberg, Donna S. ;
Soiffer, Robert ;
Dranoff, Glenn ;
Ritz, Jerome ;
Nikiforow, Sarah .
CANCER IMMUNOLOGY RESEARCH, 2019, 7 (01) :100-112
[4]   T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma [J].
Brudno, Jennifer N. ;
Maric, Irina ;
Hartman, Steven D. ;
Rose, Jeremy J. ;
Wang, Michael ;
Lam, Norris ;
Stetler-Stevenson, Maryalice ;
Salem, Dalia ;
Yuan, Constance ;
Pavletic, Steven ;
Kanakry, Jennifer A. ;
Ali, Syed Abbas ;
Mikkilineni, Lekha ;
Feldman, Steven A. ;
Stroncek, David F. ;
Hansen, Brenna G. ;
Lawrence, Judith ;
Patel, Rashmika ;
Hakim, Frances ;
Gress, Ronald E. ;
Kochenderfer, James N. .
JOURNAL OF CLINICAL ONCOLOGY, 2018, 36 (22) :2267-+
[5]   Chimeric Antigen Receptor-T Cell Therapy Practical Considerations for Implementation in Europe [J].
Buechner, Jochen ;
Kersten, Marie Jose ;
Fuchs, Miriam ;
Salmon, Florence ;
Jager, Ulrich .
HEMASPHERE, 2018, 2 (01)
[6]   Updated Phase 1 Results of a First-in-Human Open-Label Study of Lcar-B38M, a Structurally Differentiated Chimeric Antigen Receptor T (CAR- T) Cell Therapy Targeting B-Cell Maturation Antigen (Bcma) [J].
Chen, Lijuan ;
Xu, Jie ;
Fu, Weijun ;
Jin, Shiwei ;
Yang, Shuangshuang ;
Yan, Sun ;
Wu, Wen ;
Liu, Yuanfang ;
Zhang, Wu ;
Weng, Xiangqin ;
Wang, Yan ;
Wang, Jin ;
Ding, Xiaoyi ;
Li, Biao ;
Zhu, Jiang ;
Chen, Zhu ;
Fan, Frank Xiao-Hu ;
Li, Jianyong ;
Hou, Jian ;
Chen, Sai-Juan ;
Mi, Jian-Qing .
BLOOD, 2019, 134
[7]   Targeting B Cell Maturation Antigen (BCMA) in Multiple Myeloma: Potential Uses of BCMA-Based Immunotherapy [J].
Cho, Shih-Feng ;
Anderson, Kenneth C. ;
Tai, Yu-Tzu .
FRONTIERS IN IMMUNOLOGY, 2018, 9
[8]   B cell maturation antigen-specific CAR T cells are clinically active in multiple myeloma [J].
Cohen, Adam D. ;
Garfall, Alfred L. ;
Stadtmauer, Edward A. ;
Melenhorst, J. Joseph ;
Lacey, Simon F. ;
Lancaster, Eric ;
Vogl, Dan T. ;
Weiss, Brendan M. ;
Dengel, Karen ;
Nelson, Annemarie ;
Plesa, Gabriela ;
Chen, Fang ;
Davis, Megan M. ;
Hwang, Wei-Ting ;
Young, Regina M. ;
Brogdon, Jennifer L. ;
Isaacs, Randi ;
Pruteanu-Malinici, Iulian ;
Siegel, Don L. ;
Levine, Bruce L. ;
June, Carl H. ;
Milone, Michael C. .
JOURNAL OF CLINICAL INVESTIGATION, 2019, 129 (06) :2210-2221
[9]   Phase 2 Study of the Response and Safety of P-Bcma-101 CAR-T Cells in Patients with Relapsed/Refractory (r/r) Multiple Myeloma (MM) (PRIME) [J].
Costello, Caitlin L. ;
Gregory, Tara K. ;
Ali, Syed Abbas ;
Berdeja, Jesus G. ;
Patel, Krina K. ;
Shah, Nina D. ;
Ostertag, Eric ;
Martin, Chris ;
Ghoddusi, Majid ;
Shedlock, Devon J. ;
Spear, Matthew A. ;
Orlowski, Robert Z. ;
Cohen, Adam D. .
BLOOD, 2019, 134
[10]  
COWAN AJ, 2019, BLOOD S, V134, DOI DOI 10.1182/BLOOD-2019-129405