Selinexor for the treatment of patients with previously treated multiple myeloma

被引:8
作者
Mo, Clifton C. [1 ]
Jagannath, Sundar [2 ]
Chari, Ajai [2 ]
Nooka, Ajay K. [3 ,4 ]
Lonial, Sagar [3 ,4 ]
Siegel, David [5 ]
Biran, Noa [5 ]
Gasparetto, Cristina [6 ]
Bahlis, Nizar J. [7 ]
Richardson, Paul [1 ]
机构
[1] Harvard Med Sch, Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA
[2] Icahn Sch Med Mt Sinai, Tisch Canc Inst, Dept Hematol & Med Oncol, New York, NY 10029 USA
[3] Emory Univ, Dept Hematol & Med Oncol, Atlanta, GA 30322 USA
[4] Emory Univ, Winship Canc Inst, Atlanta, GA 30322 USA
[5] Hackensack Univ, John Theurer Canc Ctr, Hackensack, NJ USA
[6] Duke Univ, Canc Ctr, Durham, NC USA
[7] Charbonneau Canc Res Inst, Calgary, AB, Canada
关键词
Exportin; multiple myeloma; penta-refractory; high-risk; selinexor; XPO1; LOW-DOSE DEXAMETHASONE; NUCLEAR EXPORT; OPEN-LABEL; SELECTIVE-INHIBITION; ORAL SELINEXOR; PHASE-I; BORTEZOMIB; EFFICACY; LENALIDOMIDE; DARATUMUMAB;
D O I
10.1080/17474086.2021.1923473
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Introduction Multiple myeloma (MM) is an increasingly treatable but still incurable hematologic malignancy. Prognosis has improved significantly over recent years, although further advances remain urgently needed, especially for patients with heavily pre-treated and resistant disease for whom there are limited options. Selinexor is a first-in-class, oral, selective inhibitor of nuclear export (SINE) compound that triggers apoptosis in malignant cells by inducing nuclear retention of oncogene messenger RNAs (mRNAs) and reactivation of tumor suppressor proteins (TSPs). In clinical studies of patients with relapsed and/or refractory MM, selinexor has demonstrated both manageable toxicity and encouraging efficacy. Areas covered This review will provide an overview of the mechanism of action of selinexor as well as the efficacy and safety data from clinical studies using selinexor for the treatment of multiple myeloma. Expert opinion Long-term outcomes for patients with MM will continue to improve due to numerous recent and imminent therapeutic advances, although critical areas of unmet need remain. Oral selinexor is likely to contribute to the meeting of these needs and the further advancement of MM therapy in a meaningful way.
引用
收藏
页码:697 / 706
页数:10
相关论文
共 70 条
[21]  
GASPARETTO C, 2020, BLOOD, V136
[22]  
Gasparetto C., 2020, J CLIN ONCOL, V38, P8510, DOI 10.1200/JCO.2020.38.15_suppl.8510
[23]  
Gasparetto C, 2020, J CLIN ONCOL, V38
[24]   Integrated safety profile of selinexor in multiple myeloma: experience from 437 patients enrolled in clinical trials [J].
Gavriatopoulou, Maria ;
Chari, Ajai ;
Chen, Christine ;
Bahlis, Nizar ;
Vogl, Dan T. ;
Jakubowiak, Andrzej ;
Dingli, David ;
Cornell, Robert F. ;
Hofmeister, Craig C. ;
Siegel, David ;
Berdeja, Jesus G. ;
Reece, Donna ;
White, Darrell ;
Lentzsch, Suzanne ;
Gasparetto, Cristina ;
Huff, Carol Ann ;
Jagannath, Sundar ;
Baz, Rachid ;
Nooka, Ajay K. ;
Richter, Joshua ;
Abonour, Rafat ;
Parker, Terri L. ;
Yee, Andrew J. ;
Moreau, Philippe ;
Lonial, Sagar ;
Tuchman, Sascha ;
Weisel, Katja C. ;
Mohty, Mohamad ;
Choquet, Sylvain ;
Unger, T. J. ;
Li, Kai ;
Chai, Yi ;
Li, Lingling ;
Shah, Jatin ;
Shacham, Sharon ;
Kauffman, Michael G. ;
Dimopoulos, Meletios Athanasios .
LEUKEMIA, 2020, 34 (09) :2430-2440
[25]   Phase IB Study of Selinexor, a First-in-Class Inhibitor of Nuclear Export, in Patients With Advanced Refractory Bone or Soft Tissue Sarcoma [J].
Gounder, Mrinal M. ;
Zer, Alona ;
Tap, William D. ;
Salah, Samer ;
Dickson, Mark A. ;
Gupta, Abha A. ;
Keohan, Mary Louise ;
Loong, Herbert H. ;
D'Angelo, Sandra P. ;
Baker, Stephanie ;
Condy, Mercedes ;
Nyquist-Schultz, Kjirsten ;
Tanner, Lanier ;
Erinjeri, Joseph P. ;
Jasmine, Francis H. ;
Friedlander, Sharon ;
Carlson, Robert ;
Unger, Thaddeus J. ;
Saint-Martin, Jean-Richard ;
Rashal, Tami ;
Ellis, Joel ;
Kauffman, Michael ;
Shacham, Sharon ;
Schwartz, Gary K. ;
Razak, Albiruni Ryan Abdul .
JOURNAL OF CLINICAL ONCOLOGY, 2016, 34 (26) :3166-+
[26]   Nucleo-cytoplasmic transport as a therapeutic target of cancer [J].
Gravina, Giovanni Luca ;
Senapedis, William ;
McCauley, Dilara ;
Baloglu, Erkan ;
Shacham, Sharon ;
Festuccia, Claudio .
JOURNAL OF HEMATOLOGY & ONCOLOGY, 2014, 7
[27]   Preclinical antitumor efficacy of selective exportin 1 inhibitors in glioblastoma [J].
Green, Adam L. ;
Ramkissoon, Shakti H. ;
McCauley, Dilara ;
Jones, Kristen ;
Perry, Jennifer A. ;
Hsu, Jessie Hao-Ru ;
Ramkissoon, Lori A. ;
Maire, Cecile L. ;
Hubbell-Engler, Benjamin ;
Knoff, David S. ;
Shacham, Sharon ;
Ligon, Keith L. ;
Kung, Andrew L. .
NEURO-ONCOLOGY, 2015, 17 (05) :697-707
[28]   Immunomodulatory Drugs in Multiple Myeloma: Mechanisms of Action and Clinical Experience [J].
Holstein, Sarah A. ;
McCarthy, Philip L. .
DRUGS, 2017, 77 (05) :505-520
[29]   Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma [J].
Jakubowiak, Andrzej J. ;
Jasielec, Jagoda K. ;
Rosenbaum, Cara A. ;
Cole, Craig E. ;
Chari, Ajai ;
Mikhael, Joseph ;
Nam, Jennifer ;
McIver, Amanda ;
Severson, Erica ;
Stephens, Leonor A. ;
Tinari, Kathryn ;
Rosebeck, Shaun ;
Zimmerman, Todd M. ;
Hycner, Tyler ;
Turowski, Agata ;
Karrison, Theodore ;
Zonder, Jeffrey A. .
BRITISH JOURNAL OF HAEMATOLOGY, 2019, 186 (04) :549-560
[30]   Consensus Induced Fit Docking (cIFD): methodology, validation, and application to the discovery of novel Crm1 inhibitors [J].
Kalid, Ori ;
Warshaviak, Dora Toledo ;
Shechter, Sharon ;
Sherman, Woody ;
Shacham, Sharon .
JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN, 2012, 26 (11) :1217-1228