Next-Generation Sequencing Revolutionizes Prognostic Capabilities in Multiple Myeloma
In patients with multiple myeloma, minimal residual disease detected by next-generation sequencing after autologous hematopoietic stem cell transplantation (HSCT) has significant prognostic value.
Autologous HSCT combined with novel therapeutic agents have shown efficacy in improving response rates and prognoses in patients with multiple myeloma. The main cause of disease-specific mortality in this population is relapse due to minimal residual disease. New technologies that identify deep molecular response to therapy—such as next-generation sequencing—are required to detect minimal residual disease.
Hiroyuki Takamatsu, MD, associate professor of hematology and respiratory medicine, Kanazawa University Graduate School of Medicine Science (Japan), and colleagues conducted a comparative study to assess the prognostic values of minimal residual disease detected by next-generation sequencing or by allele-specific oligonucleotide-polymerase chain reaction (ASO-PCR). The retrospective analysis included autograft and bone marrow samples from 125 newly-diagnosed patients with multiple myeloma who underwent high-dose melphalan plus autologous HSCT.
Median follow-up for survivors was 3.5 years. Results of the study were published in Annals of Oncology (online July 27, 2017; doi:10.1093/annonc/mdx340).
Among the next-generation sequencing of post-HSCT bone marrow cells (n = 51 patients), those found to be minimal residual disease-negative (n = 26) had significantly better 4-year progression-free survival (PFS) and overall survival (OS) than those found to be minimal residual disease-positive (n = 25 patients).
After restricting the analysis to complete response cases (n = 39), patients with next-generative sequencing who were negative showed a significantly better PFS than those who were positive. Moreover, negative status in post-HSCT bone marrow cases had better PFS than positive-status cases where minimal residual disease was not detected by ASO-PCR.
Patients whose autografts were negative by next-generation sequencing had a 92% PFS rate and a 100% OS rate at 4-years post-HSCT, whereas those with positive-status who received novel agents had a better PFS and OS than those who were untreated.
“Low-level minimal residual disease detected by next-generation sequencing-based platform, but not ASO-PCR, has significant prognostic value when assessing either the autograft product or bone marrow cells post-autologous HSCT,” Dr Takamatsu and colleagues wrote. “These findings, particularly regarding the significance of minimal residual disease negativity in autograft, should be confirmed in prospective studies.”—Zachary Bessette