SOHO State of the Art Updates and Next Questions: Tailoring Upfront Therapy in Mantle Cell Lymphoma

In this article, we will review current strategies for the front-line management of mantle cell lymphoma, an uncommon and biologically and clinically heterogeneous subtype of non-Hodgkin lymphoma that remains incurable with current therapies. Patients invariably relapse with time, and as a result, treatment strategies involve persistent therapy over the course of months to years, including induction, consolidation, and maintenance. Topics discussed include the historical development of various chemoimmunotherapy backbones with continued modifications to maintain and improve efficacy while limiting off-target, off-tumor effects. Chemotherapy-free induction regimens were developed initially for elderly or less fit patients though are now being utilized for younger, transplant-eligible patients due to deeper, more prolonged remission durations with fewer toxicities. The historic paradigm of recommending autologous hematopoietic cell transplant for fit patients in complete or partial remission is now being challenged based in part on ongoing clinical trials in which minimal residual disease directed approaches influence the consolidation strategy for any particular individual. The addition of novel agents, namely first and second generation Bruton tyrosine kinase inhibitors as well as immunomodulatory drugs, BH3 mimetics, and type II glycoengineered anti-CD20 monoclonal antibodies have been tested in various combinations with or without immunochemotherapy. We will attempt to help the reader by systematically explaining and simplifying the various approaches for treating this complicated group of disorders.