Evolving Strategies for the Treatment of T-Cell Lymphoma: A Systematic Review and Recent Patents

Laribi, Kamel; Alani, Mustapha; Truong, Catherine; Materre, Alix Baugier de

doi:10.2174/1574892813666180517102801

Cited by 3 publications

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“…Clinical trials are ongoing and should clarify the place of immune checkpoint in AITL treatment. In addition, further targeted therapies are being developed and tested in ongoing clinical trials and are reviewed by others 12,95,[113][114][115] .…”

Section: Therapeutic Optionsmentioning

confidence: 99%

New preclinical models for angioimmunoblastic T-cell lymphoma: filling the GAP

et al. 2020

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Mouse models are essential to study and comprehend normal and malignant hematopoiesis. The ideal preclinical model should mimic closely the human malignancy. This means that these mice should recapitulate the clinical behavior of the human diseases such as cancer and therapeutic responses with high reproducibility. In addition, the genetic mutational status, the cell phenotype, the microenvironment of the tumor and the time until tumor development occurs, should be mimicked in a preclinical model. This has been particularly challenging for human angioimmunoblastic lymphoma (AITL), one of the most prominent forms of peripheral T-cell lymphomas. A complex network of interactions between AITL tumor cells and the various cells of the tumor microenvironment has impeded the study of AITL pathogenesis in vitro. Very recently, new mouse models that recapitulate faithfully the major features of human AITL disease have been developed. Here, we provide a summary of the pathology, the transcriptional profile and genetic and immune-phenotypic features of human AITL. In addition, we give an overview of preclinical models that recapitulate more or less faithfully human AITL characteristics and pathology. These recently engineered mouse models were essential in the evaluation of novel therapeutic agents for possible treatment of AITL, a malignancy in urgent need of new treatment options. Angioimmunoblastic T-cell lymphoma: a challenging complex malignancy Clinical aspects Angioimmunoblastic T-cell lymphoma (AITL) belongs since 2016 after revision of the world health organization (WHO) classification to the nodal T-cell lymphomas with follicular helper T-cell (Tfh) phenotype 1. AITL is a rare, aggressive lymphoma with little treatment options. Overall survival is generally poor with a five-year median survival rate of 32% 2,3. It represents only 1-2% of the non-Hodgkin's lymphomas. However, AITL appears to be the most prevalent PTCL, representing up to 35% of the noncutaneous peripheral T-cell lymphomas 2,4-6. AITL pathology develops late in life with a median age at onset of 59-65 years and patients display a generalized lymphoadenopathy 7,8. Seventy percent of the patients have bone marrow involvement and unfortunately early stage detection of AITL is very uncommon (10%) 9. Disease symptoms resemble closely an infection inducing immunologic hyper-activation (fever, rash, loss of weight, hemolytic anemia 2,5) (Fig. 1). AITL has particular clinical and pathological features, associated with splenomegaly, hepatomegaly and enlarged lymph nodes showing effacement of normal architecture and appearance of endothelial venules 3 (Fig. 1). Other typical clinical manifestation of AITL are cutaneous lesions also called skin rash in 20-50% of the patients and accumulation of abdominal ascites 5,10-13. These patients often test positive for autoimmunity including detection of rheumatoid factor, anti-smooth muscle, and nuclear autoantibodies 14. They also present a general increase in immunoglobulins called hypergammaglobulemia (30%) 7,12 .

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Section: Therapeutic Optionsmentioning

confidence: 99%

New preclinical models for angioimmunoblastic T-cell lymphoma: filling the GAP

et al. 2020

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“…T-cell lymphomas represent a diverse group of non-Hodgkin lymphomas of mature T-cell origin that generally are associated with unfavorable prognosis [1]. However, recent breakthroughs have allowed a better understanding of pathogenetic mechanisms of T-cell lymphomagenesis and uncovered molecular alterations that can be assessed using new biomarker approaches and can be specifically targeted with documented improvements in outcomes [2]. A particularly promising area in which significant progress has been made is the role of epigenetic alterations, including dysregulation of DNA methylation and histone modifications, in T-cell lymphomagenesis.…”

Section: Introductionmentioning

confidence: 99%

Targeting epigenetic regulators in the treatment of T-cell lymphoma

Ahmed

Feldman

2020

Expert Review of Hematology

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Introduction:T-cell lymphomas represent a broad group of malignant T-cell neoplasms with marked molecular, clinical, and biologic heterogeneity. Survival rates after conventional chemotherapy regimens are poor for most subtypes and new therapies are needed. Rapidly expanding knowledge in the field of epigenomics and the development of an increasing number of epigenetic modifying agents have created new opportunities for epigenetic therapies for patients with this complex group of diseases. Areas covered:The present review summarizes current knowledge on epigenetic alterations in T-cell lymphomas, availability and mechanisms of action of epigenetic modifying agents, results of clinical trials of epigenetic therapies in T-cell lymphomas, status of FDA approval, and biomarker approaches to guide therapy. Promising future directions are discussed.Expert commentary: Mutations in epigenetic modifying genes are among the most common genetic alterations in T-cell lymphomas, highlighting the potential for epigenetic therapies to improve management of this group of diseases. Single-agent efficacy is well documented, leading to FDA approval for several indications, but overall response rates and durability of responses remain modest. Critical next steps for the field include optimizing combination therapies that incorporate epigenetic modifying agents and developing predictive biomarkers that help guide patient and drug selection.

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