Risk profiling of patients with relapsed/refractory diffuse large B-cell lymphoma by measuring circulating tumor DNA

Abstract

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 + 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 versus 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 (> median) baseline ctDNA MMPM was independently prognostic for shorter PFS (adjusted 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 (n=13) than those without complete response (n=10); P=0.0025. Baseline ctDNA assessment may identify patients at high risk of progression, and should be further evaluated as a monitoring tool in R/R DLBCL. ClinicalTrials.gov identifier: NCT02257567.

Frequency of Complete Remission With R-CHOP Therapy in Patients With Diffuse Large B Cell Lymphoma

“…However, we observed that patients with a lower BMI had a higher frequency of CR than those with a higher BMI (66.7 & 81.4% vs 51.3%, p = 0.002). This finding is in contrast to some studies that reported a positive correlation between BMI and CR in patients with DLBCL [ 23 ], but in agreement with others that found no association or a negative correlation [ 24 ]. The possible mechanisms underlying the relationship between BMI and CR are not clear, but may involve the pharmacokinetics of R-CHOP drugs, the inflammatory status of obese patients, or the tumor microenvironment.…”

Target Antigen Attributes and Their Contributions to Clinically Approved Antibody-Drug Conjugates (ADCs) in Haematopoietic and Solid Cancers

“…However, the lack of correlation between CD79b expression (as measured by IHC) and the clinical response to Polivy ® [ 87 ] suggests that further research is required to elucidate suitable biomarkers to predict the response to Polivy ® . One potential prognostic tool is the level of circulating tumour DNA (ctDNA) in the periphery, with high baseline ctDNA being an indicator of a high risk of lymphoma progression [ 92 ].…”

Early Noninvasive Tracking of Response to Targeted Therapy in Non-Small Cell Lung Cancer

“…A key challenge of ctDNA based liquid biopsy approaches is identifying the optimal way to represent tumor load. Some reports have quanti ed ctDNA serially as allele frequency (AF), and some others have evaluated mutant molecules per mL plasma (MMPM) 8,9 . In our study, we assessed ctDNA dynamics during multiple time points across standard of care therapy in 25 patients with advanced NSCLC.…”