Hypermutated ctDNA: A Marker of Checkpoint Inhibitor Response?

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Patients with high alteration number in variants of unknown significance had better outcomes.
Patients with high alteration number in variants of unknown significance had better outcomes.

(HealthDay News) -- For patients with diverse malignancies, hypermutated blood-derived circulating tumor DNA (ctDNA) is associated with checkpoint inhibitor response, according to a study published online in Clinical Cancer Research.

Yulian Khagi, MD, from the University of California San Diego Moores Cancer Center in La Jolla, and colleagues assessed 69 patients with diverse malignancies who received checkpoint inhibitor-based immunotherapy and blood-derived ctDNA next-generation sequencing testing of 54 to 70 genes. Based on total and variants of unknown significance (VUS) alterations, the rates of stable disease for at least 6 months, partial and complete response (PR and CR), progression-free survival (PFS), and overall survival (OS) were assessed.

The researchers found that significant improvement in PFS was seen for high versus low alteration number in VUS (greater than 3 versus 3 or fewer alterations), with stable disease for at least 6 months/PR/CR of 45 and 15%, respectively. The results were similar for high versus low total alteration number (characterized plus VUS, greater than or equal to 6 versus fewer than 6). High VUS alteration status also correlated with statistically significant OS improvement. Responders versus nonresponders with VUS greater than 3 had a median PFS of 23 versus 2.3 months in two-month landmark analysis.

"Given the association of alteration number on liquid biopsy and checkpoint inhibitor-based immunotherapy outcomes, further investigation of hypermutated ctDNA as a predictive biomarker is warranted," the authors write.

Several authors disclosed financial ties to the biopharmaceutical industry.

Reference

Khagi Y, Goodman AM, Daniels GA, et al. Hypermutated circulating tumor DNA: Correlation with response to checkpoint inhibitor–based immunotherapy. Clin Cancer Res; 23(19); 5729–36

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