Tazemetostat: a treatment option for relapsed/refractory follicular lymphoma

被引:9
作者
Mondello, Patrizia [1 ]
Ansell, Stephen M. [1 ]
机构
[1] Mayo Clin, Div Hematol & Internal Med, Rochester, MN USA
关键词
EZH2; epigenetics; follicular lymphoma; precision therapy; tazemetostat; NON-HODGKIN-LYMPHOMA; CHRONIC LYMPHOCYTIC-LEUKEMIA; SELECTIVE-INHIBITION; GERMINAL-CENTERS; EZH2; MUTATIONS; OPEN-LABEL; HIGH-RISK; MULTICENTER; PROGRESSION; FREQUENT;
D O I
10.1080/14656566.2021.2014815
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Introduction Follicular lymphoma (FL) is the second most common form of B cell lymphoma and generally presents as an indolent and relatively slow-growing tumor. However, most FLs are incurable with a shortening of subsequent responses. Therefore, novel and more effective treatments are desperately needed. Tazemetostat is a first-in-class, selective, oral inhibitor of EZH2, a lysine methyltransferase that is mutated in about 25% of FL. Tazemetostat has been recently approved for relapsed/refractory FL after two or more lines of therapy in the presence of an EZH2 mutation or independent of an EZH2 mutation in the absence of other options. Areas covered Here, the authors provide a review focusing on the molecular mechanisms of EZH2, clinical development of tazemetostat and other EZH2 inhibitors (EZH2i), as single-agent therapy and in combinatorial regimens. Finally, they provide a futuristic look at therapeutic approaches for this disease. Expert opinion Tazemetostat monotherapy showed clinically meaningful and durable responses with a favorable toxicity profile, especially in EZH2 mutant lymphoma. Future studies should explore mechanism-based combinatorial regimens to maximize and prolong the anti-lymphoma effect.
引用
收藏
页码:295 / 301
页数:7
相关论文
共 51 条
[1]  
Andorsky DJ, 2020, J CLIN ONCOL, V38
[2]   Germinal centres and B cell lymphomagenesis [J].
Basso, Katia ;
Dalla-Favera, Riccardo .
NATURE REVIEWS IMMUNOLOGY, 2015, 15 (03) :172-184
[3]   Follicular lymphoma in the modern era: survival, treatment outcomes, and identification of high-risk subgroups [J].
Batlevi, Connie L. ;
Sha, Fushen ;
Alperovich, Anna ;
Ni, Ai ;
Smith, Katy ;
Ying, Zhitao ;
Soumerai, Jacob D. ;
Caron, Philip C. ;
Falchi, Lorenzo ;
Hamilton, Audrey ;
Hamlin, Paul A. ;
Horwitz, Steven M. ;
Joffe, Erel ;
Kumar, Anita ;
Matasar, Matthew J. ;
Moskowitz, Alison J. ;
Moskowitz, Craig H. ;
Noy, Ariela ;
Owens, Colette ;
Palomba, Lia M. ;
Straus, David ;
von Keudell, Gottfried ;
Zelenetz, Andrew D. ;
Seshan, Venkatraman E. ;
Younes, Anas .
BLOOD CANCER JOURNAL, 2020, 10 (07)
[4]   Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response [J].
Beguelin, Wendy ;
Teater, Matt ;
Meydan, Cem ;
Hoehn, Kenneth B. ;
Phillip, Jude M. ;
Soshnev, Alexey A. ;
Venturutti, Leandro ;
Rivas, Martin A. ;
Calvo-Fernandez, Maria T. ;
Gutierrez, Johana ;
Camarillo, Jeannie M. ;
Takata, Katsuyoshi ;
Tarte, Karin ;
Kelleher, Neil L. ;
Steidl, Christian ;
Mason, Christopher E. ;
Elemento, Olivier ;
Allis, C. David ;
Kleinstein, Steven H. ;
Melnick, Ari M. .
CANCER CELL, 2020, 37 (05) :655-+
[5]   EZH2 enables germinal centre formation through epigenetic silencing of CDKN1A and an Rb-E2F1 feedback loop [J].
Beguelin, Wendy ;
Rivas, Martin A. ;
Fernandez, Maria T. Calvo ;
Teater, Matt ;
Purwada, Alberto ;
Redmond, David ;
Shen, Hao ;
Challman, Matt F. ;
Elemento, Olivier ;
Singh, Ankur ;
Melnick, Ari M. .
NATURE COMMUNICATIONS, 2017, 8
[6]   EZH2 Is Required for Germinal Center Formation and Somatic EZH2 Mutations Promote Lymphoid Transformation [J].
Beguelin, Wendy ;
Popovic, Relja ;
Teater, Matt ;
Jiang, Yanwen ;
Bunting, Karen L. ;
Rosen, Monica ;
Shen, Hao ;
Yang, Shao Ning ;
Wang, Ling ;
Ezponda, Teresa ;
Martinez-Garcia, Eva ;
Zhang, Haikuo ;
Zheng, Yupeng ;
Verma, Sharad K. ;
McCabe, Michael T. ;
Ott, Heidi M. ;
Van Aller, Glenn S. ;
Kruger, Ryan G. ;
Liu, Yan ;
McHugh, Charles F. ;
Scott, David W. ;
Chung, Young Rock ;
Kelleher, Neil ;
Shaknovich, Rita ;
Creasy, Caretha L. ;
Gascoyne, Randy D. ;
Wong, Kwok-Kin ;
Cerchietti, Leandro ;
Levine, Ross L. ;
Abdel-Wahab, Omar ;
Licht, Jonathan D. ;
Elemento, Olivier ;
Melnick, Ari M. .
CANCER CELL, 2013, 23 (05) :677-692
[7]   Phase I trial of low dose decitabine targeting DNA hypermethylation in patients with chronic lymphocytic leukaemia and non-Hodgkin lymphoma: dose-limiting myelosuppression without evidence of DNA hypomethylation [J].
Blum, Kristie A. ;
Liu, Zhongfa ;
Lucas, David M. ;
Chen, Ping ;
Xie, Zhiliang ;
Baiocchi, Robert ;
Benson, Donald M. ;
Devine, Steven M. ;
Jones, Jeffrey ;
Andritsos, Leslie ;
Flynn, Joseph ;
Plass, Christoph ;
Marcucci, Guido ;
Chan, Kenneth K. ;
Grever, Michael R. ;
Byrd, John C. .
BRITISH JOURNAL OF HAEMATOLOGY, 2010, 150 (02) :189-195
[8]   EZH2 mutations are frequent and represent an early event in follicular lymphoma [J].
Boedoer, Csaba ;
Grossmann, Vera ;
Popov, Nikolay ;
Okosun, Jessica ;
O'Riain, Ciaran ;
Tan, King ;
Marzec, Jacek ;
Araf, Shamzah ;
Wang, Jun ;
Lee, Abigail M. ;
Clear, Andrew ;
Montoto, Silvia ;
Matthews, Janet ;
Iqbal, Sameena ;
Rajnai, Hajnalka ;
Rosenwald, Andreas ;
Ott, German ;
Campo, Elias ;
Rimsza, Lisa M. ;
Smeland, Erlend B. ;
Chan, Wing C. ;
Braziel, Rita M. ;
Staudt, Louis M. ;
Wright, George ;
Lister, T. Andrew ;
Elemento, Olivier ;
Hills, Robert ;
Gribben, John G. ;
Chelala, Claude ;
Matolcsy, Andras ;
Kohlmann, Alexander ;
Haferlach, Torsten ;
Gascoyne, Randy D. ;
Fitzgibbon, Jude .
BLOOD, 2013, 122 (18) :3165-3168
[9]   Germinal center dysregulation by histone methyltransferase EZH2 promotes lymphomagenesis [J].
Caganova, Marieta ;
Carrisi, Chiara ;
Varano, Gabriele ;
Mainoldi, Federica ;
Zanardi, Federica ;
Germain, Pierre-Luc ;
George, Laura ;
Alberghini, Federica ;
Ferrarini, Luca ;
Talukder, Asoke K. ;
Ponzoni, Maurilio ;
Testa, Giuseppe ;
Nojima, Takuya ;
Doglioni, Claudio ;
Kitamura, Daisuke ;
Toellner, Kai-M. ;
Su, I-hsin ;
Casola, Stefano .
JOURNAL OF CLINICAL INVESTIGATION, 2013, 123 (12) :5009-5022
[10]   Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study [J].
Casulo, Carla ;
Byrtek, Michelle ;
Dawson, Keith L. ;
Zhou, Xiaolei ;
Farber, Charles M. ;
Flowers, Christopher R. ;
Hainsworth, John D. ;
Maurer, Matthew J. ;
Cerhan, James R. ;
Link, Brian K. ;
Zelenetz, Andrew D. ;
Friedberg, Jonathan W. .
JOURNAL OF CLINICAL ONCOLOGY, 2015, 33 (23) :2516-U55