Novelties in the management of B-cell malignancies: B-cell receptor signaling inhibitors and lenalidomide

Abstract

B-cell lymphoproliferative disorders comprise 85% of Non-Hodgkin's lymphomas. Despite successful chemoimmunotherapy regimens, responses are not durable and the outcome is fatal in a considerable portion of patients. There is an inevitable need for less toxic and more potent therapeutic agents. Over the recent years, a plethora of agents including monoclonal antibodies, Bcl-2 antagonists, tyrosine kinase inhibitors, cyclin-dependent kinase inhibitors, mTOR inhibitors and immunomudulatory drugs have been developed in B-cell malignancies. The aim of this paper is to focus on B-cell receptor signaling inhibitors and lenalidomide as an immunomodulatory drug and to provide insight on how and when to incorporate these agents into the treatment algorithms.

Keywords:

• B-cell malignancy
• B-cell receptor signaling pathway inhibitor
• duvelisib
• fostamatinib
• ibrutinib
• idelalisib
• immunomodulatory drugs
• lenalidomide
• non-Hodgkin’s lymphoma

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Enhanced understanding of disease mechanisms in B-cell malignancies brings out the critical role of BCR signaling pathway. BCR signaling pathway inhibitors and immunomodulatory agents have significant efficacy in relapsed/refractory and high-risk diseases and create a new promise for chemotherapy-free management of patients with B-cell malignancies.

• Correct assessment of therapy outcomes with these new agents necessitates the modification of the current response criteria.

• Specific side effects may be predictable for certain classes of novel agents.

• Understanding the resistance mechanisms is of enormous importance for appropriate treatment approaches.

• Future studies with these agents should focus on combination and maintenance strategies and on their role as a bridge to transplantation.

• Data from ongoing studies will define the status of signaling pathway inhibitors and immunomodulatory drugs better.

• Treatment costs are a very important issue and define accessibility to the novel agents, especially in resource-constrained countries. Patients who will mostly benefit from these agents should be identified carefully.

Notes