In a German study reported in the Journal of Clinical Oncology, Mutter et al found that circulating tumor DNA (ctDNA) identified prior to and during treatment was associated with poorer outcomes in patients with central nervous system (CNS) lymphoma.
Study Details
The study included 92 patients with CNS lymphoma continuously enrolled between January 2016 and April 2021 at the University Medical Center Freiburg, Germany. Plasma and cerebrospinal fluid (CSF) samples were assessed by ultrasensitive targeted next-generation sequencing.
Key Findings
Prior to treatment, ctDNA was detectable in 61 (78%) of 78 plasma and 24 (100%) of 24 CSF samples. Among ctDNA-positive patients, 82% had disease progression at 1 year and 78% died within 2 years, whereas 68% with undetectable ctDNA were progression-free at 1 year and 90% were alive at 2 years. Hazard ratios were 4.6 (P < .0001) for progression-free survival and 9.6 (P = .0001) for overall survival. On multivariate analysis including established clinical and radiographic risk factors, higher continuous pretreatment ctDNA levels were associated with poorer progression-free survival (HR = 1.4, P = .03) and overall survival (HR = 1.6, P = .006).
Among 28 patients undergoing ctDNA profiling of their plasma samples collected during curative-intent induction immunochemotherapy, those who were ctDNA-positive at any time during treatment had significantly poorer progression-free survival (HR = 6.2, P = .0002) and overall survival (HR = 7.9, P = .004) vs those who were ctDNA-negative during treatment.
As noted by the investigators, CNS lymphoma diagnosis often remains unconfirmed due to contraindications to invasive biopsies. A proof-of-principle machine-learning approach for biopsy-free CNS lymphoma diagnosis based on ctDNA levels and ctDNA mutation profiles yielded a classifier that showed sensitivities for identifying CNS lymphoma of 59% in CSF samples and 25% in plasma samples. The classifier showed 100% specificity and positive predictive value in samples from patients with non-CNS lymphoma brain cancers.
The investigators concluded, “We demonstrate robust and ultrasensitive detection of ctDNA at various disease milestones in CNS lymphoma. Our findings highlight the role of ctDNA as a noninvasive biomarker and its potential value for personalized risk stratification and treatment guidance in patients with CNS lymphoma.”
Florian Scherer, MD, of the Department of Hematology and Oncology, University Medical Center Freiburg, Germany, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Else Kröner-Fresenius-Stiftung, Deutsche Forschungsgemeinschaft, and others. For full disclosures of the study authors, visit ascopubs.org.
