Non-invasive Tumor Immunoglobulin Gene Next Generation Sequencing (IgNGS) in Diffuse Large B Cell Lymphoma (DLBCL)

Fundació Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau

Status

Unknown

Conditions

Lymphoma, Large B-Cell, Diffuse

Treatments

Diagnostic Test: IgNGS from circulating tumor DNA

Study type

Observational

Funder types

Other

Identifiers

NCT04237168

IIBSP-LIN-2019-83

Details and patient eligibility

About

This study will evaluate IgNGS at different time points in newly diagnosed DLBCL patients homogeneously treated (RCHOP) to address its correlation with conventional techniques (i.e., positron emission tomography/computed tomography imaging (PET/CT) and outcome.

Full description

In B-cell malignancies, every lymphocyte clone expresses a unique antigen receptor structure, therefore immunoglobulin gene rearrangements (the sequence of nucleotides at the V(D)J recombination site) serves as a specific marker for each clone. Methods of analysis have changed over time to improve the sensitivity and to allow its application in clinical settings.

Diffuse Large B-cell lymphoma (DLBCL) displays molecular heterogeneity. In this context, IgNGS allows for detection of tumor clonotype from plasma (ctDNA) (Liquid Biopsy-LB) of DLBCL patients with high sensitivity and specificity. ctDNA can be tracked with this methodology in the vast majority (>90%) of patients, in contrast to NGS-methods based on genotyping for specific DLBCL mutations, which have overall low frequency. Furthermore, most newly discovered neoantigens in lymphoma derive from immunoglobulin variable sequences, supporting the relevance of the analysis of this particular region in contrast to the use of specific B-cell mutations. Importantly, preliminary studies on clonotype detection by IgNGS at the end of treatment correlate with outcome (poorer progression-free survival) and the persistence or reemergence of the tumor clonotype by ctDNA studies may anticipate the clinical relapse. We propose to evaluate IgNGS at different time points in newly diagnosed DLBCL patients treated with RCHOP to address its correlation with conventional techniques (i.e., PET/CT imaging) and outcome.

Enrollment

30 estimated patients

Sex

All

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria: patients diagnosed with de novo DLBCL, all ages, treated with R-CHOP. Patients with DLBCL not otherwise specified (NOS) according to World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues (WHO) 2016 would be included. In addition, those with "high-grade B cell lymphoma (including both NOS and those with Myc and bcl2 and/or bcl6 alterations) will be also included.

Exclusion Criteria:

Primary mediastinal DLBCL.
Transformed DLBCL
Patients HIV+
Central Nervous System (CNS) DLBCL
All other DLBCL not included under "NOS" classification, according to WHO 2016 (except those specifically indicated in "inclusion criteria").