Dr Cremolini on the Utility of xM and xM NeXT Personal Dx MRD Assays

Chiara Cremolini, MD, PhD, associate professor in medical oncology, the University of Pisa; president, Gruppo Oncologico Nord Ovest (GONO), Fondazione GONO, discusses the utilization the tumor-naive xM assay and the tumor-informed xM NeXT Personal® Dx assay for detecting minimal residual disease and early cancer recurrence, and for monitoring immunotherapy treatment response in patients with cancer.

The xM tumor-naive, plasma-based test, which is now available for clinical use, rapidly identifies circulating tumor DNA (ctDNA) post-surgery in patients with cancer, such as early-stage colorectal cancer (CRC), refining MRD testing accuracy. NeXT Personal Dx is an ultra-sensitive test designed to detect up to 1800 somatic variants unique to a patient's tumor, aiding treatment decisions for early-stage non–small cell lung cancer (NSCLC) and breast cancer, and for monitoring immunotherapy response in patients with late-stage solid tumors.

Notably, at the 2024 ASCO Annual Meeting, investigators presented data from a subgroup analysis of the GALAXY study (UMIN000039205) in the CIRCULATE-Japan platform, which demonstrated the longitudinal effectiveness of xM in patients with resected stage II or III CRC. Findings showed that the assay demonstrated a longitudinal sensitivity of 83.3% (95% CI, 67.2%-93.6%) and a longitudinal specificity of 89.5% (95% CI, 75.2%-97.1%) among all evaluable patients with CRC (n = 74).

This tumor-naive test has a rapid turnaround time, Cremolini emphasizes, noting that this eliminates the need for tissue sample collection and analysis as a preliminary step in assessing ctDNA. Although the assay did not demonstrate groundbreaking sensitivity in the landmark timepoint (LMT) analysis—which involved 1 liquid biopsy collected 4 weeks post-surgery—the sensitivity of the test increased during the longitudinal analysis, she reports. The longitudinal analysis included LMT samples and all other evaluable longitudinal samples. The longitudinal sensitivity, coupled with consistently high specificity in both the LMT and longitudinal evaluations, positions the test as a valuable tool for identifying patients in need of adjuvant chemotherapy or intensified therapy based on ctDNA status, Cremolini explains.

Although this analysis showed encouraging results in longitudinal sensitivity, Cremolini concludes by stating that it is not currently appropriate to make a treatment decision based solely on testing 1 sample collected 4 weeks post-surgery.