Biomarkers and novel therapeutic approaches for diffuse large B-cell lymphoma in the era of precision medicine

Abstract

Despite the great efforts for better treatment options for diffuse large B-cell lymphoma (DLBCL) (most common form of non-Hodgkin lymphoma, NHL) to treat and prevent relapse, it continues to be a challenge. Here, we present an overview of DLBCL and address the diagnostic assays and molecular techniques used in its diagnosis, role of biomarkers in detection, treatment of early and advanced stage DLBCL, and novel drug regimens. We discuss the significant biomarkers that have emerged as essential tools for stratifying patients according to risk factors and for providing insights into the use of more targeted and individualized therapeutics. We discuss techniques such as gene expression studies, including next-generation sequencing, which have enabled a more understanding of the complex pathogenesis of DLBCL and have helped determine molecular targets for novel therapeutic agents. We examine current treatment approaches, outline the findings of completed clinical trials, and provide updates for ongoing clinical trials. We highlight clinical trials relevant to the significant fraction of DLBCL patients who present with complex cases marked by high relapse rates. Supported by an increased understanding of targetable pathways in DLBCL, clinical trials involving specialized combination therapies are bringing us within reach the promise of an effective cure to DLBCL using precision medicine. Optimization of therapy remains a crucial objective, with the end goal being a balance between high survival rates through targeted and personalized treatment while reducing adverse effects in DLBCL patients of all subsets.

Diagnostic Performance of PD-L1 versus PD-1 Expression in Circulating CD20 Cells in Diffuse Large B-Cell Lymphoma

“…Diffuse large B-cell lymphoma (DLBCL) is the prevalent type of non-Hodgkin lymphoma (NHL), representing about 37% of NHL patients [1][2][3]. DLBCL is an aggressive type of lymphoma accompanied by significant heterogeneity in molecular genetics and clinicopathological features [4]. DLBCL is categorized into two types: germinal center B-cell (GCB type) and non-GCB type [1,5,6].…”

LAG3 and PD1 Regulate CD8+ T Cell in Diffuse Large B-cell Lymphoma Patients

“…Diffuse large B-cell lymphomas (DLBCL) account for approximately 30-40% of non-Hodgkin lymphomas (NHL) [1]. DLBCL is an aggressive lymphoma with significant heterogeneity in clinicopathological and molecular genetic features [2]. Many of the genetic mutations that occur in DLBCL affect genes involved in chromatin remodeling as well as other epigenetic functions [3].…”

“…Systemic chemotherapy with R-CDOP (rituximab, cyclophosphamide, vindesine, doxorubicin liposome, and prednisone) could reportedly achieve complete remission [8]. R-DA-EPOCH (rituximab, doxorubicin, etoposide, prednisone, vincristine, cyclophosphamide) was commonly used for relapsed DLBCL patients [2]. However, existing methods maynot accurately or effectively predict therapeutic efficacy before treatment of DLBCL [9].…”

Novel Immune-Based treatments for Diffuse Large B-Cell Lymphoma: The Post-CAR T Cell Era

“…While multiple targets are currently evaluated in clinical trials for treatment of DLBCL such as NF-κB and PI3K/AKT/mTORC pathways, Bruton’s tyrosine kinase (BTK), Spleen tyrosine kinase (SYK), enhancer of zeste hormone 2 (EZH2), phosphoinositide-3-kinase (PI3K), Janus Kinases (JAK), and anti-apoptotic proteins (e.g. BCL2, MCL1) ( 27 , 28 ), we will mainly focus on immune-based therapeutic interventions. Immunotherapy is a promising cancer treatment that relies on the identification of suitable cell surface molecules ( 29 ).…”