Aggressive T-cell lymphomas: 2019 updates on diagnosis, risk stratification, and management.

INTRODUCTION: Aggressive T-cell lymphomas continue to have a poor prognosis. There are over 27 different subtypes of peripheral T-cell lymphoma (PTCL) and we are now beginning to understand the differences between the various subtypes beyond histologic variations. MOLECULAR PATHOGENESIS OF VARIOUS SUBTYPES OF PTCL: Gene expression profiling can help in diagnosis and prognostication of various subtypes including PTCL-nos and anaplastic large cell lymphoma. In addition, mutational analysis is now being incorporated in clinical trials of novel agents to evaluate various biomarkers of response to allow better therapeutic choices for patients. TARGETED THERAPIES: There are many targeted agents currently in various stages of clinical trials for PTCL that take advantage of the differential expression of specific proteins or receptors in PTCL tumors. The most promising is the CD30 directed antibody drug conjugate brentuximab vedotin. This has recently been approved by the Food and Drug Administration for the upfront treatment of CD30 expressing PTCLs in combination with cyclophosphamide, doxorubicin, and prednisone chemotherapy. Other notable targets are CD25, CCR4 tag, PI3kinase inhibitors, and JAK/STAT inhibitors. Anaplastic lymphoma kinase (ALK) inhibitors are promising for ALK expressing tumors. IMMUNOTHERAPIES: The use of checkpoint inhibitors in the treatment of PTCL is still controversial. The most promising results have been seen in cases of extranodal natural killer cell/T-cell lymphomas and cutaneous T-cell lymphomas. For all other subtypes, immune checkpoint inhibitors should be used with extreme caution and only in the context of a clinical trial. Allogeneic stem cell transplant continues to be the curative therapy for most aggressive subtypes of PTCL.