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ctDNA and Treatment Outcome in Diffuse Large B-Cell Lymphoma

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Key Points

  • Baseline ctDNA was associated with treatment outcome.
  • Reductions in ctDNA were associated with molecular response.

In a study reported in the Journal of Clinical Oncology, Kurtz et al found that baseline circulating tumor DNA (ctDNA) and molecular response to treatment were independent predictors of treatment outcome in diffuse large B-cell lymphoma.

Study Details

The association of ctDNA with treatment outcomes was assessed in 217 patients treated at 6 sites in North America and Europe using training and validation sets. Prior to treatment, ctDNA was detectable in 98% of patients.

ctDNA, Molecular Response, and Outcomes

Pretreatment levels of ctDNA as a continuous variable were associated with both event-free and overall survival in patients receiving frontline or salvage therapy. Using a threshold value of 2.5 log hGE/mL of ctDNA, patients with high levels had significantly poorer event-free survival at 24 months vs those with low levels in both front-line (hazard ratio [HR] = 2.6, P = .007) and salvage settings (HR = 2.9, P = .01); high levels were also predictive of poorer overall survival in the salvage setting. In multivariate analysis, pretreatment ctDNA remained prognostic for event-free survival in patients receiving front-line treatment when controlling for International Prognostic Index (IPI), molecular subtype, and total metabolic tumor volume (P = .018).

In a discovery set, ctDNA levels decreased rapidly during treatment, with early molecular response (EMR) being associated with a 2-log decrease after one cycle of treatment and major molecular response (MMR) being associated with a 2.5-log decrease after two cycles. In a validation set, front-line therapy achieving EMR (83% vs 50%, P = .0015) or MMR (82% vs 46%, P < .001) was associated with improved event-free survival at 24 months; EMR was also associated with improved 24-month event-free survival in patients receiving salvage therapy in the validation set (100% vs 13%, P = .011). In multivariate analysis including IPI and results of interim positron emission tomography/computed tomography scans, molecular response (EMR or MMR) was associated with improved event-free survival (P < .0001) and overall survival (P = .029).

The investigators concluded, “Pretreatment ctDNA levels and molecular responses are independently prognostic of outcomes in aggressive lymphomas. These risk factors could potentially guide future personalized risk-directed approaches.”

The study was supported by the Damon Runyon Cancer Research, American Society of Hematology scholar award, German Research Foundation, Conquer Cancer Foundation of ASCO, National Cancer Institute, and others.

Ash A. Alizadeh, MD, PhD, of Stanford University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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