Phase II Study of Single-Agent and Combination Everolimus and Panobinostat in Relapsed or Refractory Diffuse Large B-Cell Lymphoma

被引：8

作者：

Islam, Prioty ^{[1
]}

Rizzieri, David ^{[1
]}

Lin, Chenyu ^{[1
]}

de Castro, Carlos ^{[1
]}

Diehl, Louis ^{[1
]}

Li, Zhiguo ^{[2
]}

Moore, Joseph ^{[1
]}

Morris, Tod ^{[1
]}

Beaven, Anne ^{[1
,3
]}

机构：

[1] Duke Univ, Div Hematol Malignancies & Cellular Therapy, Med Ctr, Durham, NC USA

[2] Duke Univ, Duke Canc Inst, Biostat Shared Resources, Durham, NC USA

[3] Univ N Carolina, Div Hematol, Chapel Hill, NC 27599 USA

来源：

CANCER INVESTIGATION | 2021年 / 39卷 / 10期

关键词：

Diffuse large B cell lymphoma; panobinostat; everolimus; mTORi; HDACi; HISTONE DEACETYLASE INHIBITORS; MAMMALIAN TARGET; RITUXIMAB; SYNERGIZES; RAD001; TRIAL; I/II;

D O I：

10.1080/07357907.2021.1983584

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Novel therapeutics are needed for patients with relapsed or refractory diffuse large B-cell lymphoma (R/R DLBCL). Everolimus is an mTOR pathway inhibitor with synergistic anti-tumor activity when combined with histone deacetylase inhibitors, such as panobinostat, in preclinical lymphoma models. In this Phase II study, we evaluated overall response rate to single and combination everolimus and panobinostat in R/R DLBCL. Fifteen patients were enrolled to single-agent and 18 to combination. One patient responded to everolimus, while none responded to panobinostat. Though 25% of patients responded to combination therapy, responses were not durable with significant toxicity. We demonstrated minimal single-agent activity and prohibitive toxicity with combination therapy.

引用

页码：871 / 879

页数：9

共 24 条

[1] Clinical outcome following autologous and allogeneic blood and marrow transplantation for relapsed diffuse large-cell non-Hodgkin's lymphoma [J].

Aksentijevich, Ivan ;

Jones, Richard J. ;

Ambinder, Richard F. ;

Garrett-Mayer, Elizabeth ;

Flinn, Ian W. .

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION, 2006, 12 (09) :965-972

[2] An overview of investigational Histone deacetylase inhibitors (HDACis) for the treatment of non-Hodgkin's lymphoma [J].

Apuri, Susmitha ;

Sokol, Lubomir .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2016, 25 (06) :687-696

[3] Phase 2 study of panobinostat with or without rituximab in relapsed diffuse large B-cell lymphoma [J].

Assouline, Sarit E. ;

Nielsen, Torsten Holm ;

Yu, Stephen ;

Alcaide, Miguel ;

Chong, Lauren ;

MacDonald, David ;

Tosikyan, Axel ;

Kukreti, Vishal ;

Kezouh, Abbas ;

Petrogiannis-Haliotis, Tina ;

Albuquerque, Marco ;

Fornika, Daniel ;

Alamouti, Sepideh ;

Froment, Remi ;

Greenwood, Celia M. T. ;

Oros, Kathleen Klein ;

Camglioglu, Errol ;

Sharma, Ayushi ;

Christodoulopoulos, Rosa ;

Rousseau, Caroline ;

Johnson, Nathalie ;

Crump, Michael ;

Morin, Ryan D. ;

Mann, Koren K. .

BLOOD, 2016, 128 (02) :185-194

[4] Panobinostat in combination with rituximab in heavily pretreated diffuse large B-cell lymphoma: Results of a phase II study [J].

Barnes, Jeffrey A. ;

Redd, Robert ;

Fisher, David C. ;

Hochberg, Ephraim P. ;

Takvorian, Tak ;

Neuberg, Donna ;

Jacobsen, Eric ;

Abramson, Jeremy S. .

HEMATOLOGICAL ONCOLOGY, 2018, 36 (04) :633-637

[5] Everolimus in combination with rituximab induces complete responses in heavily pretreated diffuse large B-cell lymphoma [J].

Barnes, Jeffrey A. ;

Jacobsen, Eric ;

Feng, Yang ;

Freedman, Arnold ;

Hochberg, Ephraim P. ;

LaCasce, Ann S. ;

Armand, Philippe ;

Joyce, Robin ;

Sohani, Aliyah R. ;

Rodig, Scott J. ;

Neuberg, Donna ;

Fisher, David C. ;

Abramson, Jeremy S. .

HAEMATOLOGICA, 2013, 98 (04) :615-619

[6] A phase 2 study of mocetinostat, a histone deacetylase inhibitor, in relapsed or refractory lymphoma [J].

Batlevi, Connie L. ;

Crump, Michael ;

Andreadis, Charalambos ;

Rizzieri, David ;

Assouline, Sarit E. ;

Fox, Susan ;

van der Jagt, Richard H. C. ;

Copeland, Amanda ;

Potvin, Diane ;

Chao, Richard ;

Younes, Anas .

BRITISH JOURNAL OF HAEMATOLOGY, 2017, 178 (03) :434-441

[7] Distinct pharmacological properties of second generation HDAC inhibitors with the benzamide or hydroxamate head group [J].

Beckers, Thomas ;

Burkhardt, Carmen ;

Wieland, Heike ;

Gimmnich, Petra ;

Ciossek, Thomas ;

Maier, Thomas ;

Sanders, Karl .

INTERNATIONAL JOURNAL OF CANCER, 2007, 121 (05) :1138-1148

[8] m-TOR inhibitors and their potential role in haematological malignancies [J].

Calimeri, Teresa ;

Ferreri, Andres J. M. .

BRITISH JOURNAL OF HAEMATOLOGY, 2017, 177 (05) :684-702

[9] Revised response criteria for malignant lymphoma [J].

Cheson, Bruce D. ;

Pfistner, Beate ;

Juweid, Malik E. ;

Gascoyne, Randy D. ;

Specht, Lena ;

Horning, Sandra J. ;

Coiffier, Bertrand ;

Fisher, Richard I. ;

Hagenbeek, Anton ;

Zucca, Emanuele ;

Rosen, Steven T. ;

Stroobants, Sigrid ;

Lister, T. Andrew ;

Hoppe, Richard T. ;

Dreyling, Martin ;

Tobinai, Kensei ;

Vose, Julie M. ;

Connors, Joseph M. ;

Federico, Massimo ;

Diehl, Volker .

JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (05) :579-586

[10] Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d'Etudes des Lymphomes de l'Adulte [J].

Coiffier, Bertrand ;

Thieblemont, Catherine ;

Van Den Neste, Eric ;

Lepeu, Gerard ;

Plantier, Isabelle ;

Castaigne, Sylvie ;

Lefort, Sophie ;

Marit, Gerald ;

Macro, Margaret ;

Sebban, Catherine ;

Belhadj, Karim ;

Bordessoule, Dominique ;

Ferme, Christophe ;

Tilly, Herve .

BLOOD, 2010, 116 (12) :2040-2045

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