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Next-Generation Sequencing and MRD Negativity in Multiple Myeloma

By: Emily Rhode
Posted: Wednesday, May 17, 2023

Assessing measurable residual disease (MRD) by next-generation sequencing at a sensitivity threshold of 10-6 is a strong prognostic tool for distinguishing better outcomes in transplantation-eligible patients with multiple myeloma, according to research published in Blood Cancer Journal. This MRD threshold seems to be associated with superior outcomes compared with those of patients who achieve MRD negativity at lower thresholds.

“These results add to the growing evidence for using [measurable] residual disease to improve the International Myeloma Working Group [IMWG} definition of complete response and its role as a strong prognostic marker for clinical trials,” concluded Rafael Fonseca, MD, of the Mayo Clinic, Phoenix, and colleagues.

The researchers retrospectively analyzed 186 patients diagnosed with multiple myeloma who underwent MRD assessment and autologous stem cell transplantation (ASCT) as front-line therapy. Of them, 34 had high-risk cytogenetics, and 18 had stage III disease, according to the Revised International Staging System (R-ISS).

At the 100-day follow-up, 119 patients (64.0%) had achieved a complete response or better, 48 (25.8%) achieved a very good partial response, 16 (8.6%) had had a partial response, 1 (0.5%) had minimal response, and 2 (1.1%) showed progressive disease. A total of 45 patients achieved MRD negativity at the assigned sensitivity threshold. Median follow-up time at cutoff was 27.5 months after ASCT, and 46 patients (24.7%) experienced disease progression based on the time to next treatment, defined as the time from ASCT until the start of a new line of therapy driven by disease progression. MRD negativity at 10-6 was the strongest predictor of longer time to next treatment (hazard ratio = 0.35; 95% confidence interval = 0.12–1.03; P = .06). There was poor agreement between MRD and PET/CT interpretation, and high-risk genetic subgroups or higher R-ISS stages were not correlated with lower MRD negativity.

Disclosure: For full disclosures of the study authors, visit

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