University Hospital Ospedale Of Circolo And Fondazione Macchi

Varese, Italy

University Hospital Ospedale Of Circolo And Fondazione Macchi

Varese, Italy
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Merli M.,University Hospital Ospedale Of Circolo And Fondazione Macchi | Ferrario A.,University Hospital Ospedale Of Circolo And Fondazione Macchi | Maffioli M.,University Hospital Ospedale Of Circolo And Fondazione Macchi | Arcaini L.,University of Pavia | Passamonti F.,University Hospital Ospedale Of Circolo And Fondazione Macchi
Expert Opinion on Investigational Drugs | Year: 2015

Introduction: The advent of the anti-CD20 mAb rituximab has opened a new era in the treatment of non-Hodgkin's lymphomas (NHL), markedly altering standard treatment strategies. Moreover, the proof-of-concept that targeting a specific lymphocyte surface antigen may induce a highly effective and safe targeted killing of malignant cells has opened the door to the development of a plethora of novel mAbs directed towards different B- and T-cell-specific antigens.Areas covered: This review discusses the recent available clinical data about new-generation anti-CD20 mAbs characterized by increased antibody- (obinutuzumab) or complement-dependent cyotoxicity (ofatumumab) as well as novel investigational agents targeting other lymphocyte antigens (e.g., CD19, CD22, CD30, CD40, CD52, CCR4), which are currently under investigation for B- and T-cell NHL treatment. In addition, antibody-drug conjugates (inotuzumab ozogamicin, brentuximab vedotin, polatuzumab vedotin), bispecific T-cell engagers (blinatumomab) and a new class of antibodies targeting cytotoxic T-lymphocyte-associated antigen 4, programmed death 1 or programmed death ligand 1 (immune checkpoint inhibitors) are specifically considered.Expert opinion: Among the novel mAbs challenging rituximab, obinutuzumab seems to be in the most advanced phase, with the results of randomized trials awaited shortly. Brentuximab vedotin is increasing its role in T-cell NHL. Furthermore, immune checkpoint inhibitors have the potential to acquire a great relevance in NHL therapy. © 2015 Informa UK, Ltd.


Merli M.,University Hospital Ospedale Of Circolo And Fondazione Macchi | Ferrario A.,University Hospital Ospedale Of Circolo And Fondazione Macchi | Maffioli M.,University Hospital Ospedale Of Circolo And Fondazione Macchi | Arcaini L.,University of Pavia | Passamonti F.,University Hospital Ospedale Of Circolo And Fondazione Macchi
Future Oncology | Year: 2015

Satisfactory treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) is not currently available and novel therapies are needed. mTOR is an intracellular kinase that is part of an aberrantly activated pathway in DLBCL. Preclinical studies in DLBCL cell lines demonstrated that everolimus, an oral selective mTOR inhibitor, induces cell cycle arrest and is synergistic with rituximab. Phase I studies indicated 10 mg daily to be the best dosing of everolimus in DLBCL. A large Phase II study in relapsed/refractory DLBCL confirmed the substantial activity (overall response rate: 30%) and good tolerability of everolimus in DLBCL, with thrombocytopenia being the main toxicity. The combination of everolimus and rituximab showed encouraging results (objective response rate: 38%; complete response: 13%), without increasing toxicity. Combination studies of everolimus with novel agents or with immunochemotherapy are underway. © 2015 Future Medicine Ltd.


PubMed | University Hospital Ospedale Of Circolo And Fondazione Macchi
Type: Journal Article | Journal: Expert opinion on investigational drugs | Year: 2015

The advent of the anti-CD20 mAb rituximab has opened a new era in the treatment of non-Hodgkins lymphomas (NHL), markedly altering standard treatment strategies. Moreover, the proof-of-concept that targeting a specific lymphocyte surface antigen may induce a highly effective and safe targeted killing of malignant cells has opened the door to the development of a plethora of novel mAbs directed towards different B- and T-cell-specific antigens.This review discusses the recent available clinical data about new-generation anti-CD20 mAbs characterized by increased antibody- (obinutuzumab) or complement-dependent cyotoxicity (ofatumumab) as well as novel investigational agents targeting other lymphocyte antigens (e.g., CD19, CD22, CD30, CD40, CD52, CCR4), which are currently under investigation for B- and T-cell NHL treatment. In addition, antibody-drug conjugates (inotuzumab ozogamicin, brentuximab vedotin, polatuzumab vedotin), bispecific T-cell engagers (blinatumomab) and a new class of antibodies targeting cytotoxic T-lymphocyte-associated antigen 4, programmed death 1 or programmed death ligand 1 (immune checkpoint inhibitors) are specifically considered.Among the novel mAbs challenging rituximab, obinutuzumab seems to be in the most advanced phase, with the results of randomized trials awaited shortly. Brentuximab vedotin is increasing its role in T-cell NHL. Furthermore, immune checkpoint inhibitors have the potential to acquire a great relevance in NHL therapy.

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