CtDNA possible biomarker to predict relapse in multiple myeloma
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Using circulating tumor DNA to predict relapse after autologous stem cell transplantation in patients with multiple myeloma showed feasibility in a study presented at the virtual ASCO Annual Meeting.
Minimal residual disease (MRD) detected by bone marrow-based assay is an important prognostic marker of relapse in multiple myeloma, according to Binod Dhakal, MD, associate professor of medicine in the division of hematology at the Medical College of Wisconsin.
“MRD in multiple myeloma is monitored by a first-pull marrow aspirate, but are limited by the spatial heterogeneity of marrow, extramedullary disease, and sampling variability of marrow aspiration. That's why sensitive, non-invasive, blood-based MRD assay is an unmet clinical need,” Dhakal said in his presentation. “Circulating tumor DNA, or ctDNA, is a non-invasive biomarker that can be utilized to predict relapse in multiple myeloma.”
In a retrospective study, researchers analyzed MRD using ctDNA in blood samples collected from 28 patients with multiple myeloma after upfront autologous stem cell transplant (AHCT).
Overall, 80 plasma timepoints were available pre- and post-AHCT, with a median follow-up of 92.4 months, and researchers used multiparameter flow cytometry at 10-4 level to examine MRD from the bone marrow biopsy. They whole-exome sequenced individual bone marrow aspirates or FFPE slides from the time of myeloma diagnosis and matched normal blood and identified somatic mutations.
Researchers performed MRD assessment at 3 months post-AHCT by ctDNA analysis using a personalized, tumor-informed assay then assessed the prognostic value of ctDNA by comparing MRD status with clinical outcomes.
Dhakal reported that ctDNA was detectable in 70.8% of pre-AHCT patients, 53.6% of post-AHCT patients at 3 months and 39.2% of patients during the surveillance phase post-AHCT.
Of the 15 patients with positive ctDNA, 93.3% relapsed during follow-up (HR = 5.64; 95% CI, 1.8-17). Patients negative for ctDNA at 3 months post-AHCT had significantly superior PFS compared with patients positive for ctDNA (median PFS: 84 months vs. 31 months). In addition, the positive predictive value for relapse among patients positive for ctDNA at 3 months post-AHCT was 93.3%, which was much higher than the 68.4% seen with multiparameter flow cytometry from the bone marrow assay.
“Patients who were ctDNA negative at all times had perhaps the best outcome,” Dhakal said. “Future prospective studies with real-time marrow using [next-generation] sequencing on ctDNA samples are needed to define the role of ctDNA in multiple myeloma and its prognostic significance.”
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Dhakal B, et al. Abstract 8029. Presented at: ASCO Annual Meeting; June 4-8, 2021 (virtual meeting).
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