Search

Introduction: Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL), with an incidence in Europe of 3.8/100.000/year. A multi-drugs chemoimmunotherapy regimen, containing rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone (R-CHOP) administrated every 21 days, is the standard therapy for DLBCL patients. The discovery of several biological features of DLBCL has encouraged the introduction of novel drugs in the treatment. Areas covered: In this article, the use of standard therapies will be reviewed and will be investigated adoption of novel drugs such as Bortezomib, Bruton's tyrosine kinase, IMiDs, Venetoclax, mTOR inhibitors and other biological agents. Expert commentary: A better knowledge of the biology of DLBCL is mandatory to tailor treatment and to ameliorate the poor prognosis of DLBCL. The addition of novel drugs to standard RCHOP should represent a modern approach in the treatment of DLBCL. Ibrutinib and lenalidomide showed important results in DLBCL and the integration of these drugs in first line treatment is under investigation. Despite encouraging results using novel drugs in the setting of relapsed/refractory DLBCL, the rate of failures still remains at 40%; for these reason, continued participation in clinical trials should be encouraged.

Mattia Novo,1 Elisa Santambrogio,2 Pio Manlio Mirko Frascione,3,4 Delia Rota-Scalabrini,1 Umberto Vitolo1 1Multidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, Torino, Italy; 2Hematology Unit, Santa Croce e Carle Hospital, Cuneo, Italy; 3Medical Oncology, Candiolo Cancer Institute, FPO-IRCCS, Torino, Italy; 4Department of Oncology, University of Turin, Torino, ItalyCorrespondence: Mattia NovoMultidisciplinary Oncology Outpatient Clinic, Candiolo Cancer Institute, FPO-IRCCS, Strada Provinciale 142 km 3.95, Candiolo, 10060, ItalyTel +39 011-993-3250Fax +39 011-9333275Email mattia.novo@ircc.itAbstract: Large B-cell lymphomas (LBCLs) constitute a subgroup of aggressive but highly curable lymphoproliferative diseases. Treatment of relapsed/refractory (R/R) patients still represents an unmet clinical need, and novel drugs and combinations are in continuous development. The pan–B cell panel of surface antigens that characterizes LBCL leads to a large umbrella of druggable targets. Monoclonal antibodies (mAbs) express their activity against lymphoma by targeting multiple tumor-specific antigens. This category consists of a number of molecules with different mechanisms of action, including naked mAbs, radioimmunoconjugates, antibody-drug conjugates, checkpoint inhibitors, and bispecific antibodies. In the last decade, apart from the well-known role of the anti-CD20 mAb rituximab, novel mAbs have led to remarkable steps forward in the treatment of R/R LBCL in monotherapy and combined with chemotherapy. Multiple studies are in development trying to bring these novel compounds into the frontline setting to empower the RCHOP effect or as alternative chemotherapy-free options for elderly/unfit patients. This review provides insight into antilymphoma mAbs, focused on the efficacy and safety of the main molecules approved or in development for LBCL andperspectives on the treatment of this disease.Keywords: diffuse large B-cell lymphoma, immunotherapy, targeted therapy, monoclonal antibodies, checkpoint inhibitors, bispecific antibodies