The Use of Biomarkers to Predict CNS Involvement in Diffuse Large B-Cell Lymphoma: a Danish Nationwide Registry Study

NCT05169203 | Completed

• 1 other identifier: Biomarkers CNS
• Study Type: observational
• Target: 2,969
• Locations: 0 countries
• Sites: N/A

Brief Summary

Diffuse Large B-cell Lymphoma (DLBCL) is a malignant, aggressive lymphoid cancer. The incidence in Denmark is approximately 450 cases per year. In 2/3 of the cases, complete remission is achieved with immunochemotherapy. The remaining 30% will experience relapse and in 5 % of the patients, this will occur in the central nervous system (CNS). CNS relapse has a very poor prognosis with an overall survival of 3-6 months. In order to identify patients at risk of CNS relapse, the CNS-IPI score is used to stratify the patients into three risk groups according to number of risk factors (low 0-1, middle 2-3 and high risk 4-6 which corresponds to 2-year CNS relapse rates of 0,6%, 3,4% and 10,2% respectively). DLBCL can be subdivided by gene expression analysis into three different types based on the cell of origin (ie the stage of the equivalent normal cell development from which the disease arises): the germinal center B-cell (GCB)-like subtype, the activated B-cell (ABC)-like subtype and unclassifiable. The subdivision is of prognostic importance as patients with GCB-like subtype have a 5-year OS of 76% vs 34% in the non-GCB group. Furthermore, studies have found a higher risk of CNS relapse in the ABC-like subtype compared to the GCB subtype0. Other gene rearrangements of potential importance to the risk of CNS relapse is "double hit" (DHL) (5-10% of newly diagnosed DLBCL patients) and MYC/BCL2 co-expressors (double expressors, DEL). Chemotherapeutic CNS prophylaxis is recommended based on the CNS-IPI stratification for the high-risk group (CNS-IPI 4-5) due to an estimated risk of CNS relapse of 10,2%. However, a relapse risk with a specificity of 10,2% results in almost 90% of the patients potentially receiving 'unnecessary' prophylactic chemotherapy with toxic side effects. One study published on data from the GOYA-trial have integrated COO into the CNS-IPI and found an increased sensitivity with a two year relapse risk of 15,2% in the high risk group. In this study we aim to validate the CNS-IPI and evaluate whether the addition of biomarkers for cell of origin (COO) and double hit (DH) DLBCL improves the prediction of later CNS relapse. This will be done through analysis of patientdata from the Danish nationwide lymphoma database, LYFO, on all patients with DLBCL diagnosed from 1.1.2014 to 1.1.2021 combined with pathology reports from the Danish Pathology registry.

Conditions

Diffuse Large B Cell Lymphoma; Diffuse Large B-Cell Lymphoma Cell of Origin; Diffuse Large B-cell Lymphoma Recurrent

Keywords

Diffuse Large B Cell Lymphoma CNS Relapse; Diffuse Large B Cell Lymphoma CNS High Grade

Outcome Measures

Primary Outcomes (1)

• Bio-CNS-IPI

  To validate the CNS-IPI and evaluate whether the addition of biomarkers for cell of origin (COO) and double hit (DH) DLBCL improves the prediction of later CNS relapse

  1.1.14-1.1.21

Secondary Outcomes (7)

• CNS-IPI 1

  1.1.14-1.1.21

• CNS-IPI 2

  1.1.14-1.1.21

• CNS-IPI 3

  1.1.14-1.1.21

• CNS-IPI 4

  1.1.14-1.1.21

• CNS-IPI 5

  1.1.14-1.1.21

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

From the Danish nationwide lymphoma database, LYFO, data will be collected on all patients with DLBCL diagnosed from 1.1.2014 to 1.1.2021. Focus will be on the patients diagnosed from 1.1.2014 until 1.1.2018, but we will apply for an additional year's data in order to include the relapse cases occurring during 2018. This will result in an total of 2969 patients equivalent to the incidence of 424 cases per year.

You may qualify if:

• Patients with DLBCL
• Age ≥ 18
• Received first line R-CHOP like immunochemotherapy from 2014-2020

You may not qualify if:

• Patients with lymphoma in the central nervous system at time of diagnosis
• Patients with transformed indolent lymphomas

Sponsors & Collaborators

• Herlev Hospital: lead
• Zealand University Hospital: collaborator
• Odense University Hospital: collaborator
• Aarhus University Hospital: collaborator
• Vejle Hospital: collaborator
• Aalborg University Hospital: collaborator
• Rigshospitalet, Denmark: collaborator

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Lars M Pedersen, MD, PdD

  Zealand University Hospital

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Consultant

Study Record Dates

• First Submitted: December 13, 2021
• First Posted: December 23, 2021
• Study Start: January 1, 2014
• Primary Completion: January 1, 2021
• Study Completion: January 1, 2021
• Last Updated: December 23, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share