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

Abstract

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.

Current Clinical Applications and Future Perspectives of Immune Checkpoint Inhibitors in Non-Hodgkin Lymphoma

“…Outcomes of patients with PTCL range from unsatisfactory to poor with current therapeutic approaches [ 143 ]; therefore, there is an unmet need for effective treatments. The variable upregulation of the PD-1/PD-L1 axis in tumor cells of many PTCL subtypes have led to studies testing the safety and efficacy of ICIs in these lymphomas.…”

All-oral metronomic DEVEC schedule in elderly patients with peripheral T cell lymphoma

“…In addition, this series reports on patients with heterogeneous entities of mature T cell lymphomas. Indeed, as recently underlined by Zain [20], there are over 27 different subtypes of peripheral T cell lymphoma and scientists are just beginning to understand the differences between the various subtypes beyond histologic variations. Thus, the clinical behaviours of PTCLs included into our study may be different.…”

Clinical Remission in a 72-Year-Old Patient with a Massive Primary Cutaneous Peripheral T-Cell Lymphoma-NOS of the Eyelid, Following Combination Chemotherapy with Etoposide Plus COP

“…As elderly patients are indicated to receive attenuated doses of chemotherapy, CHOP-based regimens represent viable options [ 4 , 5 ]. Still, considering that our patient had cardiac comorbidities, we chose to remove anthracyclines from the combination treatment and replaced it with etoposide.…”

“…Cutaneous lymphomas exhibit various clinical, histological, immunophenotypic, and genetic features. Moreover, they differ in prognosis and treatment from systemic lymphomas with similar histological features [ 5 , 6 , 7 , 8 ]. Up to 75–80% of cutaneous lymphomas originate from T-cells, and only 20–25% from B-cells [ 9 , 10 , 11 ].…”