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Therapeutic options in peripheral T cell lymphoma.

ABSTRACT: Peripheral T cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphomas with a very poor prognosis. The standard first-line treatments have resulted in unsatisfactory patient outcomes. With the exception of low-risk anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), the majority of patients relapse rapidly; the current 5-year overall survival rates are only 10-30%. Novel targeted therapies and combination chemotherapies are required for the treatment of patients with PTCL. In recent years, some retrospective and prospective studies have been performed concerning PTCL. Consequently, a number of novel agents and their relevant combination therapies have been identified, including histone deacetylase inhibitors, immunoconjugates, antifolates, monoclonal antibodies, immunomodulatory agents, nucleoside analogs, proteasome inhibitors, kinase inhibitors, bendamustine, L-asparaginase, and other targeted agents. It is hoped that these innovative approaches will finally improve outcomes in patients with PTCL. This review summarizes the currently available approaches for the treatment of PTCL with an emphasis on potential new agents, including the role of stem cell transplantation.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC4830033 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Therapeutic options in peripheral T cell lymphoma.

Zhang Yaping Y Xu Wei W Liu Hong H Li Jianyong J

Journal of hematology & oncology 20160412

Peripheral T cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphomas with a very poor prognosis. The standard first-line treatments have resulted in unsatisfactory patient outcomes. With the exception of low-risk anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), the majority of patients relapse rapidly; the current 5-year overall survival rates are only 10-30%. Novel targeted therapies and combination chemotherapies are required for the trea ...[more]

PMID: 27071634

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Project description:Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma with typically aggressive behavior. The genetic signature is the chromosomal translocation t(11;14)(q13;q32) resulting in overexpression of cyclin D1. Asymptomatic newly diagnosed MCL patients with low tumor burden can be closely observed, deferring therapy to the time of disease progression. Although MCL classically responds to upfront chemotherapy, it remains incurable with standard approaches. For patients in need of frontline therapy, the initial decision is whether to proceed with an intensive treatment strategy or a non-intensive treatment strategy. In general, given the unfavorable risk-benefit profile, older MCL patients should be spared intensive strategies, while younger and fit patients can be considered for intensive strategies. The bendamustine and rituximab (BR) regimen is becoming an increasingly popular treatment option among the elderly population, with improved progression-free survival (PFS) and acceptable side-effect profile. Although rituximab maintenance after R-CHOP improves survival outcomes in elderly patients, no clinical trial to date has shown statistical significance to support the use of rituximab maintenance after BR induction in older patients. In young and fit patients with MCL, an intensive strategy to maximize the length of first remission has emerged as a worldwide standard of care. With current high-dose cytarabine-containing immunochemotherapy regimens followed by autologous stem cell transplantation, the median PFS has exceeded 7 years. In the relapsed or refractory (R/R) setting, reduced intensity conditioning allogeneic hematopoietic stem cell transplantation may offer the highest likelihood of long-term survival in young R/R MCL patients, at the cost of increased risk of non-relapse mortality and chronic graft versus host disease. Novel agents targeting activated pathways in MCL cells, such as bortezomib, lenalidamide, ibrutinib and temsirolimus are now available for the management of R/R disease.

Project description:Extranodal NK/T-cell lymphoma (ENKTCL) is a highly aggressive mature NK/T-cell neoplasm marked by NK-cell phenotypic expression of CD3ε and CD56. While the disease is reported worldwide, there is a significant geographic variation with its highest incidence in East Asian countries possibly related to the frequent early childhood exposure of Epstein-Barr virus (EBV) and specific ethnic-genetical background, which contributes to the tumorigenesis. Historically, anthracycline-based chemotherapy such as CHOP (cyclophosphamide, adriamycin, vincristine, and prednisone) was used, but resulted in poor outcomes. This is due in part to intrinsic ENKTCL resistance to anthracycline caused by high expression levels of P-glycoprotein. The recent application of combined modality therapy with concurrent or sequential radiation therapy for early stage disease, along with non-anthracycline-based chemotherapy regimens consisting of drugs independent of P-glycoprotein have significantly improved clinical outcomes. Particularly, this neoplasm shows high sensitivity to l-asparaginase as NK-cells lack asparagine synthase activity. Even still, outcomes of patients with advanced stage disease or those with relapsed/recurrent disease are dismal with overall survival of generally a few months. Thus, novel therapies are needed for this population. Clinical activity of targeted antibodies along with antibody-drug conjugates, such as daratumumab (naked anti-CD38 antibody) and brentuximab vedotin (anti-CD30 antibody conjugated with auristatin E), have been reported. Further promising data have been shown with checkpoint inhibitors as high levels of programmed death-ligand 1 expression are observed in ENKTCL due to EBV-driven overexpression of the latent membrane proteins [latent membrane protein 1 (LMP1) and LMP2] with activation of the NF-κB/MAPK pathways. Initial case series with programmed death 1 inhibitors showed an overall response rate of 100% in seven relapsed patients including five with a complete response (CR). Furthermore, cellular immunotherapy with engineered cytotoxic T lymphocytes targeted against LMP1 and LMP2 have shown encouraging results with durable CRs as either maintenance therapy after initial induction chemotherapy or in the relapsed/refractory setting. In this paper, we review this exciting field of novel immunotherapy options against ENKTCL that hopefully will change the treatment paradigm in this deadly disease.

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Therapeutic options in peripheral T cell lymphoma.

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Therapeutic options in peripheral T cell lymphoma.

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