Good-Risk Group of Patients With Myeloma Saw Better Outcomes – Cancer Therapy Advisor

Researchers have used deep whole-genome sequencing (WGS) to identify genomic markers of a good-risk group of patients with multiple myeloma with prolonged survival. Specifically, patients found to have a low genomic scar score and chromosome 9 gain had superior outcomes.

In the study, researchers analyzed WGS data from a 2009 study from 183 patients with newly diagnosed myeloma who had been treated with lenalidomide, bortezomib, and dexamethasone alone or in combination with autologous stem cell transplant. These data were then integrated with clinical data.

The researchers calculated a genomic scar score (GSS) using allele-specific copy-number alterations. Patients with a total score of 5 or less were considered to have a low GSS.

On average, WGS identified 7343 single nucleotide variants, 235 small insertions, and 376 deletions per patient. Significant variations in mutational load were found, with hyperdiploid myeloma having the lowest and t(14;16) myeloma having the highest load (P =.004).

In all, patients with a low GSS had significantly longer median progression-free survival and overall survival than other patients. The researchers identified a genomically defined subgroup of patients accounting for about 17% of patients with low DNA damage (a low genomic scar score with chromosome 9 gain) and a superior outcome. These patients had 100% overall survival at 69 months.

Other characteristics of this subgroup included lower mutational load with significant contribution from age-related mutations and NRAS mutation. Specifically, patients with low GSS and chromosome 9 gain had significantly lower mutational load compared with other groups (P =.0002).

Interestingly, the superior outcome group identified here was independent of traditional clinical risk factors, such as ISS, response to treatment, and achievement of [minimal residual disease] negativity, the researchers wrote. Importantly, our study shows that, in addition to traditional risk markers, we can use genomic markers such as low GSS and gain9 to identify true low-risk groups.

Reference

Samur MK, Samur AA, Fulciniti M, et al. Genome-wide somatic alterations in multiple myeloma reveal a superior outcome group [published online July 20, 2020]. J Clin Oncol. doi: 10.1200/jco.20.00461

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Good-Risk Group of Patients With Myeloma Saw Better Outcomes – Cancer Therapy Advisor