In a Scandinavian study reported in the Journal of Clinical Oncology, Tobiasson et al found that individual-patient measurable residual disease (MRD) could be assessed by next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) to predict outcomes in patients with myelodysplastic syndrome (MDS) following hematopoietic stem cell transplantation (HSCT).
As stated by the investigators, “Early detection of MRD would enable preemptive treatment and potentially [reduce] relapse risk.”
Study Details
Two hundred and sixty-six patients from sites in Sweden, Denmark, Norway, and Finland were enrolled in the study between August 2016 and January 2020. Bone marrow and peripheral blood samples were collected until relapse, death, or end of study at 24 months after HSCT, and evaluated by a targeted NGS panel and ddPCR.
Key Findings
Among all 266 patients, estimated relapse-free survival and overall survival at 3 years after HSCT were 59% and 64%, respectively.
MRD results were available for 221 patients. Relapse was preceded by positive marrow MRD in 42 of 44 relapses with complete MRD data by a median of 71 days (range = 23–283 days). Among 137 patients in continuous complete remission, 93 consistently had undetectable MRD, 39 reverted from having detectable to undetectable MRD, and 5 had detectable MRD at last sampling. Using MRD cutoff levels of 0.1%, 0.3%, and 0.5%, estimated 1-year relapse-free survival after first detectable MRD finding was 49%, 39%, and 30%, respectively.
On multivariate analysis, factors significantly associated with shorter relapse-free survival were detectable MRD status (hazard ratio [HR] = 7.99, P < .001), World Health Organization subgroup acute myeloid leukemia (HR = 4.87, P < .001), mutant vs wild-type NRAS (HR = 3.55, P = .007), and acute grade III to IV graft-vs-host disease (GVHD; HR = 4.13, P < .001). Detectable MRD was significantly associated with shorter overall survival (HR = 2.65, P = .004). In analysis of 100 patients with detectable MRD, chronic GVHD was associated with longer relapse-free survival (HR = 0.32).
The investigators concluded, “Assessment of individualized MRD using NGS [and] ddPCR is feasible and can be used for early detection of relapse. [Detectable] MRD is associated with shorter relapse-free survival and overall survival.”
Magnus Tobiasson, MD, PhD, of the Karolinska Institutet, Stockholm, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the Knut and Alice Wallenberg Foundation, Swedish Cancer Society, Celgene Inc, and others. For full disclosures of the study authors, visit ascopubs.org.
