Novel Agents in the Treatment of Chronic Lymphocytic Leukemia: A Review About the Future

被引：15

作者：

Desai, Anjali Varma ^{[1
]}

El-Bakkar, Hassan ^{[1
]}

Abdul-Hay, Maher ^{[1
]}

机构：

[1] NYU, Langone Med Ctr, Inst Canc, Div Hematol & Med Oncol, New York, NY 10016 USA

来源：

CLINICAL LYMPHOMA MYELOMA & LEUKEMIA | 2015年 / 15卷 / 06期

关键词：

B cell lymphoma 2 inhibitors; Bruton tyrosine kinase inhibitors; CDK inhibitors; Immunomodulators; PI3K inhibitors; DEPENDENT KINASE INHIBITOR; BRUTONS TYROSINE KINASE; PHASE-II TRIAL; T-CELLS; B-CELLS; UNTREATED PATIENTS; INITIAL THERAPY; RITUXIMAB; LENALIDOMIDE; FLUDARABINE;

D O I：

10.1016/j.clml.2014.09.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Half of a century ago, physicians managing chronic lymphocytic leukemia (CLL) recognized some of its presenting features such as lymphocytosis, lymphadenopathy, and splenomegaly. Subsequently, an enhanced understanding of the disease mechanisms involved in CLL led to new, more targeted treatments. There is now a plethora of treatments available for CLL. In this review article we discuss in detail several of the novel agents that are being studied or approved for the treatment of CLL including: phosphatidylinositol 3-kinase inhibitors (idelalisib and IPI-145), Bruton tyrosine kinase inhibitors (ibrutinib), B cell lymphoma 2 inhibitors (ABT-263 and ABT-199), new anti-CD20 monoclonal antibodies (obinutuzumab), cyclin-dependent kinase inhibitors (flavopiridol and dinaciclib), immunomodulators (lenalidomide) and chimeric antigen receptor T-cell therapy.

引用

页码：314 / 322

页数：9

共 64 条

[21] Chemoimmunotherapy With Fludarabine (F), Cyclophosphamide (C), and Rituximab (R) (FCR) Versus Bendamustine and Rituximab (BR) In Previously Untreated and Physically Fit Patients (pts) With Advanced Chronic Lymphocytic Leukemia (CLL): Results Of a Planned Interim Trial, International, Randomized Study Of The German CLL Study Group (GCLLSG) [J].

Eichhorst, Barbara ;

Fink, Anna-Maria ;

Busch, Raymonde ;

Lange, Elisabeth ;

Koeppler, Hubert ;

Kiehl, Michael ;

Soekler, Martin ;

Schlag, Rudolf ;

Vehling-Kaiser, Ursula ;

Koechling, Georg ;

Ploeger, Christoph ;

Gregor, Michael ;

Plesner, Torben ;

Trneny, Marek ;

Fischer, Kirsten ;

Doehner, Hartmut ;

Kneba, Michael ;

Wendtner, Clemens ;

Klapper, Wolfram ;

Kreuzer, Karl-Anton ;

Stilgenbauer, Stephan ;

Boettcher, Sebastian ;

Hallek, Michael .

BLOOD, 2013, 122 (21)

[22] First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia [J].

Eichhorst, Barbara F. ;

Busch, Raymonde ;

Stilgenbauer, Stephan ;

Stauch, Martina ;

Bergmann, Manuela A. ;

Ritgen, Matthias ;

Kranzhoefer, Nicole ;

Rohrberg, Robert ;

Soeling, Ulrike ;

Burkhard, Oswald ;

Westermann, Anne ;

Goede, Valentin ;

Schweighofer, Carmen D. ;

Fischer, Kirsten ;

Fink, Anna-Maria ;

Wendtner, Clemens M. ;

Brittinger, Guenter ;

Doehner, Hartmut ;

Emmerich, Bertold ;

Hallek, Michael .

BLOOD, 2009, 114 (16) :3382-3391

[23] The PI3-Kinase Delta Inhibitor Idelalisib (GS-1101) Targets Integrin-Mediated Adhesion of Chronic Lymphocytic Leukemia (CLL) Cell to Endothelial and Marrow Stromal Cells [J].

Fiorcari, Stefania ;

Brown, Wells S. ;

McIntyre, Bradley W. ;

Estrov, Zeev ;

Maffei, Rossana ;

O'Brien, Susan ;

Sivina, Mariela ;

Hoellenriegel, Julia ;

Wierda, William G. ;

Keating, Michael J. ;

Ding, Wei ;

Kay, Neil E. ;

Lannutti, Brian J. ;

Marasca, Roberto ;

Burger, Jan A. .

PLOS ONE, 2013, 8 (12)

[24] Bendamustine in Combination With Rituximab for Previously Untreated Patients With Chronic Lymphocytic Leukemia: A Multicenter Phase II Trial of the German Chronic Lymphocytic Leukemia Study Group [J].

Fischer, Kirsten ;

Cramer, Paula ;

Busch, Raymonde ;

Boettcher, Sebastian ;

Bahlo, Jasmin ;

Schubert, Joeerg ;

Pflueger, Karl H. ;

Schott, Silke ;

Goede, Valentin ;

Isfort, Susanne ;

von Tresckow, Julia ;

Fink, Anna-Maria ;

Buehler, Andreas ;

Winkler, Dirk ;

Kreuzer, Karl-Anton ;

Staib, Peter ;

Ritgen, Matthias ;

Kneba, Michael ;

Doehner, Hartmut ;

Eichhorst, Barbara F. ;

Hallek, Michael ;

Stilgenbauer, Stephan ;

Wendtner, Clemens-Martin .

JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (26) :3209-3216

[25] Bendamustine Combined With Rituximab in Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia: A Multicenter Phase II Trial of the German Chronic Lymphocytic Leukemia Study Group [J].

Fischer, Kirsten ;

Cramer, Paula ;

Busch, Raymonde ;

Stilgenbauer, Stephan ;

Bahlo, Jasmin ;

Schweighofer, Carmen D. ;

Boettcher, Sebastian ;

Staib, Peter ;

Kiehl, Michael ;

Eckart, Michael J. ;

Kranz, Gabriele ;

Goede, Valentin ;

Elter, Thomas ;

Buehler, Andreas ;

Winkler, Dirk ;

Kneba, Michael ;

Doehner, Hartmut ;

Eichhorst, Barbara F. ;

Hallek, Michael ;

Wendtner, Clemens-Martin .

JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (26) :3559-3566

[26] Idelalisib and Rituximab in Relapsed Chronic Lymphocytic Leukemia [J].

Furman, Richard R. ;

Sharman, Jeff P. ;

Coutre, Steven E. ;

Cheson, Bruce D. ;

Pagel, John M. ;

Hillmen, Peter ;

Barrientos, Jacqueline C. ;

Zelenetz, Andrew D. ;

Kipps, Thomas J. ;

Flinn, Ian ;

Ghia, Paolo ;

Eradat, Herbert ;

Ervin, Thomas ;

Lamanna, Nicole ;

Coiffier, Bertrand ;

Pettitt, Andrew R. ;

Ma, Shuo ;

Stilgenbauer, Stephan ;

Cramer, Paula ;

Aiello, Maria ;

Johnson, Dave M. ;

Miller, Langdon L. ;

Li, Daniel ;

Jahn, Thomas M. ;

Dansey, Roger D. ;

Hallek, Michael ;

O'Brien, Susan M. .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (11) :997-1007

[27] Chemotherapy-induced augmentation of T cells expressing inhibitory receptors is reversed by treatment with lenalidomide in chronic lymphocytic leukemia [J].

Gassner, Franz J. ;

Zaborsky, Nadja ;

Neureiter, Daniel ;

Huemer, Michael ;

Melchardt, Thomas ;

Egle, Alexander ;

Rebhandl, Stefan ;

Catakovic, Kemal ;

Hartmann, Tanja N. ;

Greil, Richard ;

Geisberger, Roland .

HAEMATOLOGICA, 2014, 99 (05) :E67-E69

[28] Relevance of CD49d protein expression as overall survival and progressive disease prognosticator in chronic lymphocytic leukemia [J].

Gattei, Valter ;

Bulian, Pietro ;

Del Principe, Maria Ilaria ;

Zucchetto, Antonella ;

Maurillo, Luca ;

Buccisano, Francesco ;

Bomben, Riccardo ;

Dal-Bo, Michele ;

Luciano, Fabrizio ;

Rossi, Francesca M. ;

Degan, Massimo ;

Amadori, Sergio ;

Del Poeta, Giovanni .

BLOOD, 2008, 111 (02) :865-873

[29] Chemoimmunotherapy with GA101 plus chlorambucil in patients with chronic lymphocytic leukemia and comorbidity: results of the CLL11 (BO21004) safety run-in [J].

Goede, V. ;

Fischer, K. ;

Busch, R. ;

Jaeger, U. ;

Dilhuydy, M-S ;

Wickham, N. ;

De Guibert, S. ;

Ritgen, M. ;

Langerak, A. W. ;

Bieska, G. ;

Engelke, A. ;

Humphrey, K. ;

Wenger, M. ;

Hallek, M. .

LEUKEMIA, 2013, 27 (05) :1172-1174

[30] PI3Kδ Inhibition by Idelalisib in Patients with Relapsed Indolent Lymphoma [J].

Gopal, Ajay K. ;

Kahl, Brad S. ;

de Vos, Sven ;

Wagner-Johnston, Nina D. ;

Schuster, Stephen J. ;

Jurczak, Wojciech J. ;

Flinn, Ian W. ;

Flowers, Christopher R. ;

Martin, Peter ;

Viardot, Andreas ;

Blum, Kristie A. ;

Goy, Andre H. ;

Davies, Andrew J. ;

Zinzani, Pier Luigi ;

Dreyling, Martin ;

Johnson, Dave ;

Miller, Langdon L. ;

Holes, Leanne ;

Li, Daniel ;

Dansey, Roger D. ;

Godfrey, Wayne R. ;

Salles, Gilles A. .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 370 (11) :1008-1018

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