In a study (DIRECT) reported in the Journal of Clinical Oncology, Krupka et al found that phased variant (PV) ctDNA provided “sensitive and clinically meaningful response assessment” after first-line treatment of large B-cell lymphoma (LBCL).
As stated by the investigators, “Tracking tumor-specific … PVs [ie, tracking these mutations as pairs or triplets within the same sequencing read] allows ultrasensitive detection of minimal residual disease (MRD) that may enhance the accuracy of response assessment.”
Study Details
The study involved 155 patients from six sites in the English National Health System who had data on PV-MRD status at end of first-line treatment; 38 patients had detectable PV-MRD and 118 had undetectable PV-MRD at the end of treatment.
Key Findings
After a median follow-up of 24.5 months, the proportions of patients with no tumor progression at 2 years were 42% among those with detectable PV-MRD at end of treatment vs 95% among those with no detectable PV-MRD at end of treatment (hazard ratio [HR] = 13.7, P < .001).
In an analysis restricted to patients who received full-dose anthracycline-based immunotherapy as first-line treatment, proportions of patients without tumor progression at 2 years were 45% among those with detectable vs 96% among those with undetectable PV-MRD at end of treatment (HR = 15.4, P < .001). Comparison with conventional radiologic response assessment showed a greater hazard ratio in predicting an absence of tumor progression at 2 years with PV-MRD (HR = 16.9 vs 6.9 for positron-emission tomography).
The limit of detection for PV-MRD with 95% confidence (LoD95) varied by more than two orders of magnitude across patients, emphasizing the importance of obtaining patient-specific LoD95.
Absence of relapse in patients with persistent PV-MRD was observed, including in three of four patients with transformed follicular lymphoma, pointing out the need for caution when interpreting positive PV-MRD.
The investigators concluded: “[End-of-treatment] PV-MRD enables sensitive and clinically meaningful response assessment in LBCL. It provides independent prognostic information, enhancing [end-of-treatment] response assessment beyond conventional radiologic assessment. Our findings support the incorporation of PV-MRD into clinical trials and routine management of diffuse LBCL.”
Daniel J. Hodson, MD, PhD, of Cancer Molecular Diagnostics Laboratory, Department of Oncology, University of Cambridge, United Kingdom, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by Cambridge University Hospitals NHS Foundation Trust, AstraZeneca, and others. For full disclosures of the study authors, visit ascopubs.org.
