Therapeutic Advances in Relapsed and Refractory Peripheral T-Cell Lymphoma

SIMPLE SUMMARY: T-cell lymphomas are a rare, heterogeneous family of lymphomas derived from post-thymic T lymphocytes. For patients with relapsed or refractory disease, outcomes are generally poor, with overall survival usually less than one year in the absence of an allogeneic hematopoietic stem cell transplantation. The historic approach to relapsed or refractory disease has been the use of non-overlapping combination chemotherapy. However, tremendous progress has been made in understanding the pathogenesis of these diseases, leading to a plethora of novel, biologically rational therapies. In this review, we provide an updated evaluation of therapeutic advances in relapsed and refractory T-cell lymphomas, focusing on approved agents and promising investigational regimens with emerging data within the last five years. We provide a basic framework for the management of disease in this setting. ABSTRACT: Historic outcomes for patients with relapsed or refractory nodal-based T-cell lymphomas are poor, with survival generally measured in months in multiple reports from the late 20th and early 21st century. Until recently, salvage strategies have mostly been borrowed from other aggressive lymphomas. However, dedicated investigations into the pathogenesis of T-cell lymphomas have resulted in an outpouring of therapies that target these diseases in biologically rational strategies. In particular, an evolving appreciation of the multiple complex oncogenic pathways and epigenetic changes that underlie these diseases has led to numerous agents targeting these aberrancies. Moreover, large reports of salvage allogeneic stem cell transplants in T-cell lymphoma have now been published, showing that adaptive immunotherapy is a potentially curative strategy for patients with relapsed or refractory disease. This review highlights therapeutic advances for relapsed or refractory T-cell lymphomas, including cellular therapy and allogeneic stem cell transplant, and provides a framework for management.