Emerging strategies in peripheral T-cell lymphoma

Abstract

Peripheral T-cell lymphomas (PTCLs) are a heterogenous group of aggressive non-Hodgkin lymphomas that are less chemosensitive than their B-cell counterparts. Until recently, standard therapy did not distinguish between subtypes, and deeper understanding of the biology of these diseases was lacking. The availability of targeted therapy and more sophisticated subtype classification has translated into the development of novel treatment options for these rare diseases. This includes the development of a brentuximab vedotin-based upfront chemotherapy regimen that confers an overall survival benefit for a subset of patients. Clinical trials of targeted agents, as well as development of better preclinical models of PTCL, are leading to therapeutic advances in the field, including the development of phosphoinositide-3-kinase inhibitors, histone deacetylase inhibitor-based strategies, CD30-directed strategies, Janus kinase inhibitors, and spleen-associated tyrosine kinase inhibitors. Better understanding of the biology of these diseases based on gene expression profiling, minimal residual disease evaluation, and modeling in patient-derived xenografts should help define mechanisms of response and resistance to therapy. Given the complex biology of these heterogeneous lymphomas, well-tolerated combination strategies targeted toward specific subtypes of PTCL can lead to advances in the field. Similar to the story of brentuximab vedotin, development of effective therapies in the salvage setting will likely lead to improved upfront strategies in PTCLs, and ultimately a more personalized approach.

Circulating tumor DNA by high‐throughput sequencing of T cell receptor monitored treatment response and predicted treatment failure in T cell lymphomas

“…Other techniques such as the Cancer Personalized Profiling by Deep Sequencing (CAPP‐seq) 29 could also be applied in further study to learn the genotyping and clone evolution of TCLs. As there have already been several novel agents proven to be effective in TCL, such as ALK inhibitors, PI3 kinase inhibitors, JAK inhibitors, and hypomethylating agents, personalized and target therapy with the help of ctDNA will be in the near future 30 …”

T follicular helper phenotype predicts response to histone deacetylase inhibitors in relapsed/refractory peripheral T-cell lymphoma

“…This phenotype was defined as having strong expression by immunohistochemistry and/or flow cytometry of at least 2 TFH markers, among CD10, CD279 (PD1), CXCL13, ICOS, SAP, CCR5, and BCL6. 2 Pathology review was performed locally at each institution. Cases of PTCL-NOS in which the tissue could not be reviewed and a minimum of at least 2 markers for TFH were not included in the report were excluded from this analysis.…”

“…Patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) have poor prognosis, with a median survival of 6 to 10 months. 1,2 Romidepsin and other histone deacetylase inhibitors (HDACi) are active agents for relapsed/refractory PTCL, achieving overall responses in around 25% of patients and median duration of response of 13 For the original deidentified data, proposal for access should be e-mailed to the corresponding author, Paola Ghione (paola.ghione@roswellpark.org). Individual participant data will not be shared.…”

“…HDACi increase the histone acetylation, which is thought to reduce the expression of tumor suppressor genes and oncogenes. 2 The recent World Health Organization (WHO) classification of lymphoid malignancies, refined the PTCL-not otherwise specified (NOS) category, introducing a subtype of PTCL defined as nodal PTCL with T follicular helper phenotype (TFH). 6 TFH-PTCL is thought to share the same cell of origin as angioimmunoblastic T-cell lymphoma (AITL), 7 because it carries a similar mutational pattern and gene expression profile that are believed to confer sensitivity to HDACi via epigenetic regulation and other different mechanism.…”

Updates in the Treatment of Peripheral T-Cell Lymphomas

“…In a phase II study involving 45 patients with PTCL and 25 with cutaneous T cell lymphoma, the ORR was 35%. 69 These early studies demonstrate that targeting the JAK/STAT pathway can be clinically beneficial for those patients. Apoptotic inhibitors.…”