Emerging predictive biomarkers for novel therapeutics in peripheral T-cell and natural killer/T-cell lymphoma

Abstract

Peripheral T-cell lymphoma (PTCL) and natural killer/T-cell lymphoma (NKTCL) are rare subtypes of non-Hodgkin’s lymphoma that are typically associated with poor treatment outcomes. Contemporary first-line treatment strategies generally involve the use of combination chemoimmunotherapy, radiation and/or stem cell transplant. Salvage options incorporate a number of novel agents including epigenetic therapies (e.g. HDAC inhibitors, DNMT inhibitors) as well as immune checkpoint inhibitors. However, validated biomarkers to select patients for individualized precision therapy are presently lacking, resulting in high treatment failure rates, unnecessary exposure to drug toxicities, and missed treatment opportunities. Recent advances in research on the tumor and microenvironmental factors of PTCL and NKTCL, including alterations in specific molecular features and immune signatures, have improved our understanding of these diseases, though several issues continue to impede progress in clinical translation. In this Review, we summarize the progress and development of the current predictive biomarker landscape, highlight potential knowledge gaps, and discuss the implications on novel therapeutics development in PTCL and NKTCL.

Novel clinical risk stratification and treatment strategies in relapsed/refractory peripheral T-cell lymphoma

“…The more recently developed indices have allowed for better distribution of patients into the risk groups for a more accurate stratification of each patient’s risk. However, these clinical indices were based on patient populations who were not treated by brentuximab as per the ECHELON-2 study nor did they take into account new molecular prognostic indicators of PTCL and its subtypes (reviewed in [ 38 ]). Consequently, the patients who do relapse post induction treatment or are primary refractory remain a challenging group of patients and novel strategies are needed to address their dismal outcomes.…”

Precise diagnosis and treatment for peripheral T-cell lymphomas: From pathogenic mechanisms to innovative approaches

“…179 The panel should include "targetable" mutations (e.g., TET2, DNMT3A, and IDH2 R172), as well as other prognostic biomarkers (e.g., TP53, PRDM1, and CDKN2A/2B). 10 The detection of characteristic mutations, such as the RHOA G17V mutation in the angioimmunoblastic form of TFH lymphoma, can also aid the diagnosis of patients with atypical pathological features. 180 Despite this understanding, the clinical impact of genomic profiling in…”

“…2 However, few of them have been translated into biomark-ers, especially therapeutic targets. [10][11][12] To address this challenge, recent research has shifted its focus from large-scale sequencing to the pathogenic mechanisms of PTCLs, which facilitates better analysis of multi-omics data and identification of targetable biomarkers. 13 By modulating specific pathogenic pathways, genes, or molecules responsible, mechanism-based precision treatment aims to enhance therapeutic efficacy while minimizing harm to healthy tissues.…”

An evidence based immunohistochemical panel for diagnosing oral lymphoma along with a case series

“…The 2016 revised World Health Organization (WHO) classification of lymphoid neoplasms classifies these lesions based on cell biology. [ 2 ] To treat lymphoma, deciphering the cell of origin is imperative for chemotherapy, radiotherapy, biologic therapy, and immunotherapy. [ 1 2 ]…”

“…[ 2 ] To treat lymphoma, deciphering the cell of origin is imperative for chemotherapy, radiotherapy, biologic therapy, and immunotherapy. [ 1 2 ]…”