Association of circulating tumor DNA from the cerebrospinal fluid with high-risk CNS involvement in patients with diffuse large B-cell lymphoma.
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ABSTRACT:
SUBMITTER: Wang X
PROVIDER: S-EPMC7809600 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Association of circulating tumor DNA from the cerebrospinal fluid with high-risk CNS involvement in patients with diffuse large B-cell lymphoma.
Wang Xiaoxiao X Gao Yan Y Shan Changguo C Lai Mingyao M He Haixia H Bai Bing B Ping Liqin L Rong Qixiang Q Ai Ruyu R Wen Lei L Zhou Zhaoming Z Yu Ruoying R Ou Qiuxiang Q Wu Xue X Wang Xiaoxia X Shao Yang W YW Cai Linbo L Huang Huiqiang H
Clinical and translational medicine 20210101 1
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Project description:Patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) have heterogeneous outcomes; durable remissions are infrequently observed with standard approaches. Circulating tumor DNA (ctDNA) assessment is a sensitive, potentially prognostic tool in this setting. We assessed baseline ctDNA to identify patients with R/R DLBCL at high risk of relapse after receiving polatuzumab vedotin and bendamustine plus rituximab (BR) or BR alone. Patients were transplant ineligible and had received ≥1 prior line of therapy. The ctDNA assay, based on a customized panel of recurrently mutated genes in DLBCL, measured mutant molecules per mL (MMPM) at baseline and end of treatment (EOT). Endpoints included progression-free survival (PFS) and overall survival (OS) in subgroups stratified by baseline ctDNA and log-fold change in ctDNA at EOT vs baseline. In biomarker-evaluable patients (n = 33), baseline ctDNA level correlated with serum lactate dehydrogenase (LDH) concentration, number of prior therapies, stage, and International Prognostic Index (IPI). After adjusting for number of prior therapies ≥2, IPI score ≥3, and LDH above the upper limit of normal, high (greater than median) baseline ctDNA MMPM was independently prognostic for shorter PFS (adjusted hazard ratio [HR], 0.18 [95% CI, 0.05-0.65]) and OS (adjusted HR, 0.20 [95% CI, 0.06-0.68]). In 23 patients with baseline and EOT samples, a significantly greater decrease in ctDNA MMPM was observed in patients with complete response (CR) (n = 13) than those without CR (n = 10); P = .0025. Baseline ctDNA assessment may identify patients at high risk of progression and should be further evaluated as a monitoring tool in R/R DLBCL. This trial was registered at www.clinicaltrials.gov as #NCT02257567.
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