Circulating tumor DNA predicts DLBCL outcomes
medwireNews: Pretreatment levels of circulating tumor (ct)DNA, as well as changes during therapy, are independently prognostic of outcomes in patients with diffuse large B-cell lymphoma (DLBCL) and can add to established risk factors, findings indicate.
The study authors explain in the Journal of Clinical Oncology that although new therapies have improved DLBCL outcomes, many patients still experience disease relapse or die. However, attempts to identify those who are likely to relapse, and who therefore need more intensive therapy, have had limited success.
To address this issue, Ash Alizadeh (Stanford University School of Medicine, California, USA) and colleagues investigated the utility of ctDNA as a prognostic marker in a cohort of 217 patients with DLBCL or primary mediastinal BCL who were undergoing treatment at one of six US or European institutions.
They found that DLBCL patients with a high pretreatment ctDNA level (>2.5 log hGE/mL) had significantly worse event-free survival (EFS) rates at 24 months than those with lower levels. This held true in both the front-line and salvage settings, with hazard ratios of 2.6 and 2.9, respectively. High ctDNA levels also predicted significantly worse overall survival (OS) in the salvage setting.
Furthermore, a 2-log drop in ctDNA levels by the start of cycle 2 (ie, 21 days after the start of therapy), which the researchers termed an “early molecular response,” was a significant prognostic factor for both EFS and OS in patients receiving front-line or salvage therapy.
Similarly, a 2.5-log drop by the start of cycle 3 – termed a “major molecular response” – was also significantly prognostic of EFS and OS in the front-line setting, but patient numbers were insufficient to evaluate its prognostic value in the salvage setting, notes the team.
While the prognostic value of molecular response was independent of established risk factors, say Alizadeh et al, patients with favorable molecular and interim positron emission tomography or computed tomography responses had “excellent outcomes.”
By contrast, those with a positive scan but no molecular response were found to be “at extremely high risk of treatment failure,” which the investigators believe “could provide an opportunity for early intervention with alternative treatments, including autologous bone marrow transplantation or chimeric antigen receptor T cells.”
Although further investigations are required, including prospective studies, the researchers envision that early milestones such as early molecular response and major molecular response “will be useful in many areas,” including as early surrogate endpoints in clinical trials of novel drugs.
“Alternatively, ctDNA quantitation could be used in clinical practice as a prognostic factor for individual patients,” they conclude.
By Catherine Booth
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