The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma

Friedberg, Jonathan W.; Vose, Julie M.; Kelly, Jennifer L.; Young, Faith; Bernstein, Steven H.; Peterson, Derick R.; Rich, Lynn; Blumel, Susan; Proia, Nicole K.; Liesveld, Jane L.; Fisher, Richard I.; Armitage, Jamés O.; Grant, Steven; Leonard, John P.

doi:10.1182/blood-2010-11-314708

Cited by 183 publications

(102 citation statements)

References 31 publications

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“…6 Preliminary clinical results suggest that bortezomib may have antitumor effects also in the GCB subtype. 6,9,10 The inhibition of proteasome may have sensitized the DLBCL cells to the cytotoxic action of the chemotherapy. Other- wise, bortezomib exhibits NF-B-independent cytotoxicity in a wide range of different tumor types 48,[51][52][53] and affects many additional pathways that may be differently used by ABC and GCB subtypes.…”

Section: Discussionmentioning

confidence: 99%

The Expression of the Endoplasmic Reticulum Stress Sensor BiP/GRP78 Predicts Response to Chemotherapy and Determines the Efficacy of Proteasome Inhibitors in Diffuse Large B-Cell Lymphoma

Mozos

Roué

López‐Guillermo

et al. 2011

The American Journal of Pathology

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Activation of the endoplasmic reticulum (ER) stress pathway is associated with poor response to doxorubicin-containing regimens, such as rituximab, cyclophosphamide, hydroxydaunorubicin (doxorubicin), vincristine and prednisone (R-CHOP), in patients with diffuse large B-cell lymphoma (DLBCL). Bortezomib, a proteasome inhibitor, interferes with ER responses and improves survival in patients with aggressive hematologic malignant tumors, although its use in DLBCL patients remains controversial. The 78-kDa glucose-regulated protein (GRP78), also known as immunoglobulin heavy chain binding protein (BiP), is an ER stress sensor involved in the resistance to doxorubicin and bortezomib, but its role in the response to chemotherapy in DLBCL has not been explored before. We show that high BiP/GRP78 expression is related to worse overall survival (median overall survival, 5.2 versus 3.4 years). Moreover, cell death after R-CHOP in DLCBL cell lines is associated with decreased BiP/GRP78 expression. Conversely, DLBCL cell lines are primarily resistant to bortezomib, probably owing to BiP/GRP78 overexpression. Small-interfering RNA silencing of BiP/GRP78 renders all cell lines sensitive to bortezomib. R-CHOP with bortezomib (R-CHOP-BZ) reduces BiP/GRP78 expression and overcomes bortezomib resistance, mimicking the small-interfering RNA silencing of BiP/ GRP78. Accordingly, R-CHOP-BZ is the most effective treatment, providing a rationale for the use of this combinational therapy to improve DLBCL patient survival. Moreover, this study provides preclinical evidence that the germinal center B-cell-like subtype DLBCL is sensitive to bortezomib combined with immunochemotherapy.

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Section: Discussionmentioning

confidence: 99%

The Expression of the Endoplasmic Reticulum Stress Sensor BiP/GRP78 Predicts Response to Chemotherapy and Determines the Efficacy of Proteasome Inhibitors in Diffuse Large B-Cell Lymphoma

Mozos

Roué

López‐Guillermo

et al. 2011

The American Journal of Pathology

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“…Recently, bortezomib [61][62][63] , lenalidomide [64][65][66] , bendamustine [67][68][69] , pixantrone 70 , azaepothilone ixabepilone 71 and mTOR inhibitor temsirolimus [72][73][74] has been shown to demonstrate activity alone and in combination with rituximab and mitoxantrone, and may induce complete responses in relapsed or refractory MCL 61,64,69,75,76 . Along with rituximab, these biotherapy agents can be used frontline or may also be introduced into post transplant maintenance to prevent or treat relapses 61,68,[77][78][79][80][81] .…”

Section: New Agentsmentioning

confidence: 99%

“…Along with rituximab, these biotherapy agents can be used frontline or may also be introduced into post transplant maintenance to prevent or treat relapses 61,68,[77][78][79][80][81] . There may be an advantage of combining rituximab with bendamustine compared to combining with the conventional CHOP regimen in terms of disease free survival 82 .…”

Section: New Agentsmentioning

confidence: 99%

Mantle Cell Lymphoma: Decision Making for Transplant

Koç¹,

Demirer²

2012

New Advances in Stem Cell Transplantation

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“…Median PFS rates are in the range of 12 months. The published combined regimens encompass both targeted approaches, such as rituximab or rituximab-dexamethasone [26,27], as well as immunochemotherapies such as rituximabdexamethasone-high dose-cytarabin (R-HAD), rituximab-prednisone-cyclophosphamide (R-CP), rituximab-bendamustine and gemcitabine [28][29][30][31]. The toxicity profile predominantly consists of polyneuropathy (sometimes marked and long lasting) and neutrothrombocytopenia (when associated with chemotherapy), challenging the long-term application, for example, as maintenance in relapsed MCL.…”

Section: Proteasome Inhibitorsmentioning

confidence: 99%

The current therapeutic scenario for relapsed mantle cell lymphoma

Ferrero

Dreyling

2013

Current Opinion in Oncology

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Purpose of reviewPatients with relapsing mantle cell lymphoma (MCL) still represent a demanding challenge for the hematooncologist. The dismal prognosis and the absence of generally accepted therapeutic standards hamper the clinical management of such cases. Moreover, the availability of many targeted approaches, in a field so far missing efficient salvage regimens, challenges current therapeutic algorithms in these patients. Recent findingsMolecular targeted drugs provide unprecedented response rates in relapsed and even chemorefractory MCL. Many phase II studies demonstrated impressive antilymphoma activity of compounds such as bortezomib, lenalidomide and temsirolimus, whereas ongoing phase III trials currently assess the 'real world' benefit and the impact on survival, both alone and in combination with chemotherapy or monoclonal antibodies. Recently, the Bruton's tyrosine kinase inhibitor ibrutinib, targeting the B-cell receptor cascade, showed impressive response rates and will be soon available in phase III trials. SummaryIn the present review we focus on the major therapeutic discoveries of the last few years to offer a practical algorithm to select the appropriate treatment in patients with relapsed MCL.

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The combination of bendamustine, bortezomib, and rituximab for patients with relapsed/refractory indolent and mantle cell non-Hodgkin lymphoma

Cited by 183 publications

References 31 publications

The Expression of the Endoplasmic Reticulum Stress Sensor BiP/GRP78 Predicts Response to Chemotherapy and Determines the Efficacy of Proteasome Inhibitors in Diffuse Large B-Cell Lymphoma

The Expression of the Endoplasmic Reticulum Stress Sensor BiP/GRP78 Predicts Response to Chemotherapy and Determines the Efficacy of Proteasome Inhibitors in Diffuse Large B-Cell Lymphoma

Mantle Cell Lymphoma: Decision Making for Transplant

The current therapeutic scenario for relapsed mantle cell lymphoma

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