Integrated analysis of next generation sequencing minimal residual disease (MRD) and PET scan in transplant eligible myeloma patients

Author:

Fonseca Rodrigo1ORCID,Arribas Mariano1ORCID,Wiedmeier-Nutor Julia E.1,Kusne Yael N.1,Gonzalez-Velez Miguel2,Kosiorek Heidi3,Butterfield Richard J.1,Kirsch Ilan4,Mikhael Joseph5,Stewart A. Keith6,Reeder Craig1ORCID,Larsen Jeremy1,Bergsagel P.7ORCID,Fonseca Rafael1ORCID

Affiliation:

1. Mayo Clinic

2. Dignity Health

3. Mayo Clinic Scottsdale

4. Adaptive Biotechnologies, Seattle, WA, USA

5. Translational Genomics Research Institute (TGen), City of Hope Cancer Center

6. Princess Margaret Cancer Centre, University Health Network, University of Toronto

7. Mayo Clinic in Arizona

Abstract

Abstract Minimal residual disease (MRD) assays allow response assessment in patients with multiple myeloma (MM), and negativity is associated with improved survival outcomes. The role of highly sensitive next generation sequencing (NGS) MRD in combination with functional imaging remains to be validated. We performed a retrospective analysis on MM patients who underwent frontline autologous stem cell transplant (ASCT). Patients were evaluated at day 100 post-ASCT with NGS MRD and positron emission tomography (PET-CT). Patients with ≥ 2 MRD measurements were included in a secondary analysis for sequential measurements. 186 patients were included in the analysis. At day 100, 45 (24.2%) patients achieved MRD negativity at a sensitivity threshold of 10− 6. MRD negativity was the most predictive factor for longer time to next treatment (TTNT). Negativity rates did not differ according to MM subtype, R-ISS Stage nor cytogenetic risk. PET-CT and MRD positivity had poor agreement. Patients with sustained MRD negativity had longer TTNT, regardless of baseline risk characteristics. Our results show that the “real world” ability to measure deeper and sustainable responses distinguishes a subpopulation of patients with better outcomes. Achieving MRD negativity was the strongest prognostic marker and could help guide therapy-related decisions and serve as a response marker for clinical trials.

Publisher

Research Square Platform LLC

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