Abstract 845TiP
Background
Primary CNS lymphomas (PCNSL) are rare malignancies that present challenges in diagnosis and assessment, with contrast-enhanced (CE) MRI being the only standard imaging technique. However, CE-MRI has limitations in staging, response assessment and prognostication. Harnessing new, sensitive technologies is crucial for surveillance and treatment decisions. We have previously showed that Contrast Clearance Analysis (CCA), which highlights active disease areas with high clearance in blue and inactive areas with low clearance in red, is a highly sensitive MRI neuroimaging tool, achieving 100% sensitivity in identifying histologically confirmed lesions. Integrating CCA holds promise in addressing the limitations CE-MRI by providing additional information crucial for accurate disease assessment. Similarly promising is detecting circulating-tumour DNA (ctDNA) mutations specific to CNS lymphoma. While cerebrospinal fluid (CSF) analysis via flow cytometry and cytopathology can aid diagnosis, they often lack sensitivity, require large CSF volumes and repeat examinations can be challenging. Plasma ctDNA offers a convenient alternative to CSF with its ease of collection, followed by enhanced sensitivity when using a tumour-informed approach. As such, liquid biopsy can play a crucial role in surveillance, serve as a prognostic indicator and a tool for early detection and assessment of minimal residual disease.
Trial design
In this single centre, prospective study, we aim to recruit 36 newly diagnosed PCNSL patients (currently 8 enrolled). Our objective is to evaluate the utility of CCA in conjunction with the standard CE-MRI at baseline and at the EoT to comprehensively assess response. Additionally, we aim to develop a ctDNA assay to explore the molecular aspects and monitor the disease. CSF (optional) collection will be offered at baseline, alongside peripheral blood and urine sampling for ctDNA analysis at baseline, end of treatment (EoT), and regular intervals over a 5-year period post-chemotherapy. Due to its rarity, data on PCNSL are limited. With this study we aim to identify novel tools such as CCA and ctDNA to better characterize PCNSL, improve the prognostic accuracy, and guide surveillance and treatment decisions.
Clinical trial identification
NCT05828628; IRAS Number: 312039.
Editorial acknowledgement
Legal entity responsible for the study
The Joyce Tiffen CNS lymphoma fund.
Funding
The Joyce Tiffen CNS lymphoma fund.
Disclosure
D. Cunningham: Financial Interests, Personal and Institutional, Funding, Research funding: Clovis, Eli Lilly, 4SC, Leap, Roche. D. El-Sharkawi: Financial Interests, Personal and Institutional, Advisory Board: AbbVie; Astex; AstraZeneca; BeiGene; Janssen; Kyowa Kirin; Lilly Roche; Sobi; Financial Interests, Personal and Institutional, Other, Honoraria: AbbVie; AstraZeneca; BeiGene; Gilead, Janssen; Roche; Takeda; Financial Interests, Personal and Institutional, Advisory Board, Conference/ Travel support: AbbVie; Novartis; Roche. S. Iyengar: Financial Interests, Personal and Institutional, Other, conference support: AbbVie; BeiGene; BMS; Takeda; Financial Interests, Personal and Institutional, Other, speaker fees: AstraZeneca; Gilead; Takeda; Financial Interests, Personal and Institutional, Advisory Board: BeiGene; Gilead; MSD; Takeda. I. Chau: Financial Interests, Personal and Institutional, Advisory Board: Eli Lilly, Bristol Myers Squibb, MSD, Roche, Merck-Serono, AstraZeneca, OncXerna, Boehringer Ingelheim, Incyte, Astella, GSK, Sotio, Eisai, Daiichi Sankyo, Taiho, Servier, Seagen, Turning Point Therapeutics, Novartis, Takeda, Elevation Oncology; Financial Interests, Personal and Institutional, Funding, Research funding: Eli Lilly, Janssen-Cilag; Financial Interests, Personal and Institutional, Other, Honorarium: Eli Lilly, Eisai, Servier, Roche. All other authors have declared no conflicts of interest.
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