A research team identified genomic markers linked to longer survival in patients with newly diagnosed multiple myeloma (MM), findings for which were published in the Journal of Clinical Oncology.

“[T]his is the first comprehensive genomic study, to our knowledge, that identifies a good-risk group in MM,” the investigators wrote in their report.

In the phase 3 IFM/DFCI 2009 trial (ClinicalTrials.gov Identifier: NCT01191060) investigators used whole-genome sequencing (WGS) to determine genomic markers of long-term survival in patients with newly diagnosed MM, and aimed to assess the genomic landscape in this patient population. Patients in this trial had received either lenalidomide, bortezomib, and dexamethasone (RVD) therapy or RVD with autologous stem cell transplantation (ASCT). Clinical outcomes were examined in comparison with WGS data.

WGS data were analyzed for 183 patients. Per patient there was a mean of 7343 single nucleotide variants (SNVs; range, 1431-42,108), a mean of 376 deletions (range, 89-765), and a mean of 235 small insertions (range, 71-495). Patients with t(14;16) MM were found to carry the greatest mutational load, while hyperdiploid MM was associated with the lowest mutational load (P =.004).


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Particular mutational processes were associated with myeloma subgroups. For hyperdiploid MM, mutational processes associated with age were more heavily represented, while patients with t(14;16) MM showed greater influence by processes associated with apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like proteins. Other patterns were identified for remaining MM subgroups.

An especially low level of DNA damage was found in a subgroup that consisted of 17% of the study population. In addition to level amounts of DNA damage, this subgroup was characterized by having chromosome 9 gain, low mutational load, and a 69-month 100% overall survival (OS) rate.

For most patients in the analysis, OS and progression-free survival (PFS) did not greatly differ between RVD and RVD+ASCT treatment arms, but for the good-risk subgroup that was identified, the addition of ASCT to RVD was significantly associated with improved PFS (P <.006).

These findings identified a good-risk MM subgroup that was marked by a reduced mutational burden and possibly limited genomic instability. “Identifying these good-risk patients will affect clinical research and inform therapeutic algorithms in the future,” the researchers concluded.

Disclosures: Some authors have declared affiliations with or received grant support from the pharmaceutical industry. Please refer to the original study for a full list of disclosures.

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