Study Sheds Light on Genetic Landscape of Resistant Multiple Myeloma
Posted: Thursday, February 27, 2020
According to research presented at the 2019 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract 365) and published in the journal Blood, a large-scale analysis of genomic data from patients with relapsed or refractory multiple myeloma has indicated a prevalence of high-risk features, such as chromosomal copy number aberrations and oncogenic drivers.
“These analyses are revealing the evolution of genetic drivers of resistance to therapy and will assist in identification of subsets of poor prognostic groups (eg, double-hit) and new molecular subsets of relapsed or refractory multiple myeloma where novel targeted therapies could be developed,” concluded Sarah Gooding, MD, PhD, of Oxford University Hospitals NHS Trust, United Kingdom, and colleagues.
The study analyzed genetic material from 485 patients with relapsed or refractory multiple myeloma. In addition, “somatic single nucleotide variants and indels were derived from whole-genome sequencing from 308 samples.” Notable translocations included t(11;14) [25%], t(8;14) [25%], t(4;14) [14%], t(14;16) [8%], t(6;14) CCND3 [6%], t(14;20) [5.5%], and t(6;14) [IRF4 5.5%]. Overall, 46% of patients (140/308) had hyperdiploidy. An increase in instances of key chromosomal copy number aberrations was noted between samples in this study and those collected from patients with newly diagnosed multiple myeloma, including del17p (17% vs. 8%) and t(11;14) (25% vs. 15%). There was a greater occurrence of high cancer cell fraction in patients with relapsed or refractory disease who had del17p than in newly diagnosed patients with del17p.
In addition, 107 driver genes were identified, including novel ones such as IGLL5 (n = 19). A total of 72 oncogenes, such as UBR4 and IRF4, and 43 tumor-suppressor genes, such as TDG and SMARCA4, were also identified. Among patients with relapsed or refractory disease, FGFR3 driver mutations were associated with t(4;14), whereas IRF4 mutations were associated with t(11;14).
Disclosure: For full disclosures of the study authors, please visit ashpublications.org.