Monoclonal Antibodies in Lymphoma

Dear Colleagues,

The introduction of monoclonal antibodies (MoAbs) into clinical practice has significantly improved the prognosis of many hematological malignancies, representing  a milestone in the field of precision medicine.

Used in monotherapy or, more often, in combination with chemotherapy, MoAbs are currently essential in the treatment of lymphoid neoplasms.

MoAbs are able to target specific cancer antigens, using direct or indirect immunological killing to address cytotoxic agents to neoplastic cells, to recruit and activate immune effector cells, and to antagonize cell exhaustion.      

In this Special Issue, we would like to provide an overview of the biological basis and the current clinical use of MoAbs and of the optimal combination regimens and sequential schemes, with a look towards future therapeutic perspectives.

Dr. Donato Mannina
Guest Editor

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• monoclonal antibodies
• immunotherapy
• drug immunoconiugates
• bispecific antibodies
• checkpoints inhibitors
• NHL
• HL
• CLL

Title: Bispecific Antibodies for Lymphoid Malignancies Treatment
Authors: Matteo Bisio; Luca Legato; Filippo Fasano; Corrado Benevolo Savelli; Carola Boccomini; Maura Nicolosi; Elisa Santambrogio; Roberto Freilone; Mattia Novo; Barbara Botto
Affiliation: Hematology Division, A.O.U. Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy
Abstract: The introduction of highly active immunotherapies has changed the outcome of B-cell non-Hodgkin lymphomas (B-NHL) in the last 2 decades. Since then, important progress was shown using newer and more active immunotherapeutics, including chimeric antigen receptor T-cell therapy (CAR-T) that currently plays a significant role in the treatment of diffuse large B cell (DLBCL), follicular (FL) and mantle cell (MCL) lymphoma. Bispecific antibodies (BsAbs) are a novel class of “off-the-shelf” T-cell redirecting drugs and are among the most promising therapeutic chance for lymphoma today. BsAbs may target various cell-surface antigens and exist in different formats. Anti-CD20xCD3 BsAbs have demonstrated significant single-agent activity in patients with heavily pretreated B-NHL with a manageable toxicity profile. New antigen targets are currently under investigation such as CD19xCD3 and CD30xCD3 or CD30xCD16 in different settings. In this review, we provide an updated overview of recently completed and ongoing BsAbs trials in patients with R/R B-NHL and Hodgkin’s disease, including single-agent results, emerging combinations, safety data and novel constructs.

Title: Next-generation therapies in Mantle cell Lymphoma (MCL): the evolving landscape in treatment of relapse/refractory after CAR-T cells
Authors: Lorenzo Comba; Rita Tavarozzi; Claudia Castellino; Elia Boccellato; Foglietta Myriam; Massaia Massimo; Alessia Castellino
Affiliation: 1. Hematology Unit, Santa Croce e Carle Hospital, Cuneo, Italy 2. University of Turin, Torino, Italy 3. Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy
Abstract: Mantle cell lymphoma (MCL) is a biological and clinical heterogeneous disease, with courses ranging from indolent cases to highly aggressive ones, with limited prognosis. Bruton Tyrosin Kynase Inhibitors (BTK-i), such as ibrutinib, ameliorated the outcome of relapse/refractory patients, but responses are usually quite short, requiring further treatments. In this setting, immunotherapy demonstrated to have a key role, first with chimeric antigen receptor (CAR)-T cells, which completely change prognosis of these patients, showing high rate and long-lasting responses. However, many cases still do not respond to CAR-T cells or relapse after the treatment or are not eligible to that kind of therapy. In this thought setting of MCL patients, next-generation therapies are emerging, such as new non-covalent BTK-i molecules, and novel monoclonal antibodies (MAB), which represent a heterogeneous group of agents, including naked antibodies, immunotoxins and T-cell engaging molecules. The impact of these agents is expected to be broad initially on R/R disease, but subsequently also in early treatment lines. The aims of this review are to explore the main therapeutic strategies emerging in the context of MCL patients, who failed or are not eligible to CAR-T cells treatment, focusing on the most relevant therapeutic drugs and above all on the different monoclonal antibodies.

Title: Bispecific Monoclonal Antibodies in Diffuse Large B-Cell Lymphoma: Dawn of a New Era in Targeted Therapy
Authors: Mattia Schipani; Matteo Bellia; Carola Sella; Mariangela Greco; Abdurraouf Mokhtar Mahmoud; Clara Deambrogi; Gianluca Gaidano; Riccardo Bruna
Affiliation: Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Azienda Ospedaliero-Universitaria Maggiore della Carità, 28100 Novara, Italy.
Abstract: Diffuse large B-cell lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL) worldwide. Currently, approximately sixty percent of patients are cured with R-CHOP as frontline treatment, while the remaining patients experience primary refractory or relapsed disease (R/R). Prognosis of R/R DLBCL patients is poor, particularly for those neither eligible for chimeric antigen receptor (CAR) T-cell therapy nor autologous stem cell transplantation (ASCT), representing a significant unmet need. The advent of bispecific monoclonal antibodies (BsMAbs), such as Bispecific T-cell engagers (BiTEs) and dual-affinity re-targeting (DART) molecules, offers a promising new therapeutic approach in the treatment of DLBCL, both as frontline treatment and in the R/R setting. BsMAbs simultaneously engage two different antigens, a tumor-associated antigen and an immune cell antigen, redirecting T-cells against lymphomatous cells and enhancing the immune response. BsMAbs represent a breakthrough therapy in the treatment of DLBCL, especially in refractory or relapsed diseases. The purpose of this article is to review the landscape of BsMAbs in DLBCL.