Assessment of Individualized MRD With NGS, ddPCR Effective for Early Detection of MDS Relapse

Evaluating individualized measurable residual disease (MRD) using next-generation sequencing (NGS) and droplet digital polymerase chain reaction (ddPCR) demonstrated feasibility and utility for early detection of relapse among patients with myelodysplastic syndrome (MDS) according to a recent study.

Eligible participants included 266 patients with MDS planned for hematopoietic stem-cell transplantation (HSCT) and were enrolled in a prospective, observational study that evaluated the association between MRD and clinical outcome. Investigators collected bone marrow and peripheral blood samples until relapse, death, or end of study 2 years following transplantation. Patient-specific mutations were then identified with a targeted NGS panel and traced using ddPCR.

Among all participants, the estimated relapse-free survival (RFS) and overall survival (OS) rates 3 years after HSCT were 59% and 64%, respectively. MRD was available for 221 patients. Relapse was preceded by positive bone marrow MRD in 42 out of 44 relapses with complete MRD data, by a median of 71 (23 to 283) days. Results demonstrated that of 137 patients in continuous complete remission, 93 were consistently MRD-negative, 39 reverted from MRD+ to MRD–, and 5 were MRD+ at last sampling. The estimated 1 year-RFS after the first positive MRD was 49%, 39%, and 30%, which used cutoff levels of 0.1%, 0.3%, and 0.5%, respectively. 

In a multivariate Cox model, MRD (hazard ratio [HR], 7.99), World Health Organization (WHO) subgroup acute myeloid leukemia (AML) (HR, 4.87), TP53 multi-hit (HR, 2.38), NRAS (HR, 3.55), and acute graft-versus-host disease (GVHD) grade 3 to 4 (HR, 4.13) were associated with shorter RFS. It was also noted that MRD+ was independently associated with a shorter OS (HR, 2.65). In a subgroup analysis of 100 MRD+ patients, presence of chronic GVHD was associated with longer RFS (HR, 0.32).

Magnus Tobiasson, MD, PhD, Department of Hematology, Karolinska University Hospital, Stockholm, Sweden, and colleagues concluded, “Assessment of individualized MRD using NGS and ddPCR is feasible and can be used for early detection of relapse.” 

“Positive MRD is associated with shorter RFS and OS,” they added. 

Source:

Tobiasson M, Pandzic T, Illman J, et al. Patient-specific measurable residual disease markers predict outcome in patients with myelodysplastic syndrome and related diseases after hematopoietic stem-cell transplantation. J Clin Oncol. Published online January 17, 2024. doi: 10.1200/JCO.23.01159