How I manage peripheral T‐cell lymphoma, not otherwise specified and angioimmunoblastic T‐cell lymphoma: current practice and a glimpse into the future

Abstract

Peripheral T-cell lymphoma (PTCL), not otherwise specified (NOS) and angioimmunoblastic T-cell lymphoma (AITL) are the most frequent of more than 20 mature PTCL entities featuring a broad spectrum of morphological, immunophenotypic, molecular and clinical characteristics. Unfortunately, recent progress in understanding the (epi)genetic background of PTCL has not been met with similar advances in treatment. Thus, CHO(E)P [cyclophosphamide, doxorubicin, vincristine, and prednisone (plus etoposide)] remains standard first-line therapy. Patients without comorbidities achieving complete or partial remission proceed to autologous stem cell transplantation. With this approach about 50% of patients survive long-term. Patients relapsing after or progressing during first-line therapy have a dismal prognosis. They receive salvage gemcitabine-therapy followed by allogeneic transplantation whenever possible. After allografting, approximately half of the patients survive long-term; any other treatment is palliative. New drugs investigated in phase II studies achieved response rates between 10% and 30%; long-term remissions are the exception to the rule. While most new drugs are not licensed and not readily available, a plethora of other innovative drugs targeting (epi-)genetic abnormalities are in early development. These, together with combinations of new and old drugs, will hopefully increase response to first-line therapy, bridge more patients to transplantation, and finally improve prognosis for all patients with PTCL.

Allogeneic hematopoietic stem cell transplantation for T-cell lymphomas

“…Although most if not all T-cell lymphomas harbor typical cytogenetic and molecular abnormalities, none of these markers has been used alone or in combination with clinical risk factors to improve on the International Prognostic Index. 13…”

“…Unfortunately, the rapidly increasing knowledge of genetic and epigenetic changes found in virtually all subtypes of T/NK-cell lymphomas 13 has not been paralleled by the pace of therapeutic innovation achieved. The cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, and prednisone (CHOP) regimen first described in 1976 14 remains the cornerstone of first-line therapy for most T-cell lymphoma patients.…”

“…New drugs such as lenalidomide, romidepsin, mogamulizumab, belinostat, or alisertib have also been investigated to improve the patient's remission status before transplant. 13 Unfortunately, except for BV in CD 30 1 disease and crizotinib in ALK 1 ALCL, survival rates have been somewhat disappointing and the search for better debulking agents before allogeneic HSCT continues. PD-1 or PD-1L antibodies show activity also in certain T-cell lymphoma entities.…”

The new biology of PTCL‐NOS and AITL: current status and future clinical impact

“…Current treatment strategies have been covered in detail by others (Dearden et al , ; Schmitz & de Leval, ) and only a summary will be presented here to provide context for the review. The lack of randomised clinical trial data demonstrating a clear standard of care has led to variations in clinic practice both nationally and internationally.…”

“…For example, multiple biopsies are sometimes necessary before a definitive diagnosis can be reached and secondly, poor concordance rates between pathologists have been described (Herrera et al, 2014;Bellei et al, 2017). Current treatment strategies have been covered in detail by others (Dearden et al, 2011;Schmitz & de Leval, 2017) and only a summary will be presented here to provide context for the review. The lack of randomised clinical trial data demonstrating a clear standard of care has led to variations in clinic practice both nationally and internationally.…”