Overview of targeted drugs for mature B-cell non-hodgkin lymphomas

The improved knowledge of pathogenetic mechanisms underlying lymphomagenesis
and the discovery of the critical role of tumor microenvironments have enabled the design
of new drugs against cell targets and pathways. The Food and Drug Administration
(FDA) has approved several monoclonal antibodies (mAbs) and small molecule inhibitors
(SMIs) for targeted therapy in hematology. This review focuses on the efficacy results
of the currently available targeted agents and recaps the main ongoing trials in the
setting of mature B-Cell non-Hodgkin lymphomas. The objective is to summarize the
different classes of novel agents approved for mature B-cell lymphomas, to describe
in synoptic tables the results they achieved and, finally, to draw future scenarios as
we glimpse through the ongoing clinical trials. Characteristics and therapeutic efficacy
are summarized for the currently approved mAbs [i.e., anti-Cluster of differentiation
(CD) mAbs, immune checkpoint inhibitors, chimeric antigen receptor (CAR) T-cell
therapy, and bispecific antibodies] as well as for SMIs i.e., inhibitors of B-cell receptor
signaling, proteasome, mTOR BCL-2 HDAC pathways. The biological disease profiling
of B-cell lymphoma subtypes may foster the discovery of innovative drug strategies for
improving survival outcome in lymphoid neoplasms, as well as the trade-offs between
efficacy and toxicity. The hope for clinical advantages should carefully be coupled with
mindful awareness of the potential pitfalls and the occurrence of uneven, sometimes
severe, toxicities.