Advanced Practice Provider Emory University Winship Cancer Institute ATLANTA, Georgia, United States
Introduction: The FDA’s Oncologic Drugs Advisory Committee (ODAC) voted 12 to 0 supporting the use of minimal residual disease (MRD) as a regulatory end point for accelerated approval of new treatments for patients with multiple myeloma. In this context, the most used MRD testing in the United States is ClonoSEQ® that leverages next generation sequencing (NGS) and polymerase chain reaction (PCR) to identify and quantify rearranged and translocated receptor gene sequences, a trackable marker of myeloma MRD burden at any given time. First, a successful diagnostic clonal identification (ID) is needed for any future MRD tracking of the identified clones. We have evaluated the rates of successful clonal ID at our institution.
Methods: We have established an institutional practice at Emory Winship Cancer Institute to send samples for clonoSEQ® identification (ID) and MRD testing. We have identified 3553 myeloma patient samples sent to Adaptive clonoSEQ® ID (N=1164) and MRD (N=2389) assessments between 01/2018 and 03/2024. We have evaluated testing by era to identify rates of detection of clonal ID: era 1 from 01/2018-12/2021 and era 2 from 01/2022-03/2024. SPSS version 29.0, Chicago was used for statistical analysis.
Results: Among the 1164 samples sent for clonal ID, the median time from the sample collection at diagnosis to ID testing was 94.71 weeks (0.14-1001.29). Median time from sample collection to ID testing differed by era of testing: era 1 vs era 2 - 121.71 weeks (0.14-1001.29) vs 47.14 weeks (0.29-804.9), p< 0.001. Median time from testing to reporting ID results is 1.43 weeks (0.71-216 weeks), which did not differ by the era 1 vs 2 - 1.29 (0.71-216 weeks) vs 1.71 (0.71-188 weeks). Diagnostic clonal identification occurred in 82.8% of patients. Failed testing (10%) and polyclonality (7.2%) were the most common reasons to prevent clonal identification. In the more recent years, after 01/2022, successful clonal identification occurred in higher number of patients. Compared from era 1 to era 2, successful clonal ID was higher (91% vs. 79%, respectively, p< 0.001), failed testing was improved (2.1% vs 13.1%, respectively, p< 0.001) while the rates of polyclonality did not differ (7.3% vs 6.9%, respectively, p=NS).
Conclusions: In aggregate, diagnostic clonal identification for assessment of future MRD testing occurred in 82.8% of patients. In the more recent years (after 01/2022), successful clonal identification by clonoSEQ® occurred in 91% of patients with a significant decline in failed testing (2.1%). This likely represents an effect of the denatured DNA samples captured from era 1. Polyclonality continues to be a major deterrent for successful clonal identification in 7% of patients. Our data informs the industry sponsors and the investigators to accurately plan for sample size estimations for future clinical trials using MRD as an endpoint.
