NGF-Based MRD Assessment Demonstrates Potential to Predict MM Disease Progression

Previous studies have produced heterogeneous results on next-generation flow (NGF)-based minimal residual disease (MRD) detection, despite improvements to the method’s reproducibility and sensitivity, prompting the present authors to investigate its clinical utility.

Results from a new study show next-generation flow (NGF)-based assessment of minimal residual disease (MRD) status to hold promise at predicting disease progression when multiple myeloma (MM) is in remission.

Findings were published recently in Annals of Laboratory Medicine, and the authors also note that patients who have high-risk cytogenetic abnormalities may benefit from this technology, which they highlight is cost-effective and can produce rapid results. However, they added, “there is considerable heterogeneity in the real-world clinical application and interpretation of results, posing a challenge for sharing and accumulating experience and data from various laboratories.”

Their investigation covered 90 patients (59, MRD negative; 31, MRD positive) from Samsung Medical Center in Korea, who provided 108 bone marrow samples and were prospectively enrolled between February 2019 and October 2020. All patients had suspected morphological remission after or during their MM treatment. Electronic medical records supplied data on protein electrophoresis, immunofixation, free light chain, and cytogenetics, and disease response was classified as stringent complete remission (sCR), complete remission (CR), and very good partial response (VGPR). For this analysis, del(17p), t(4;14)(p16;q32), or t(14;16)(q32;q23) were the high-risk cytogenetic abnormalities.

The most common myeloma subtype was immunoglobulin G (48.9%), and among those with light chain only disease, 60.7% had the Kappa light chain type. Overall, the median (IQR) limit of detection following NGF-based MRD assessment was 0.0003% (0.0002%-0.0005%); the median limit of quantification, 0.0007% (0.0006%-0.0011%); and median MRD, 0.015% (0.006%-0.072%).

Abnormal plasma cells also exhibited the following aberrant markers: CD45–, CD19–, and monoclonal CyIgKappa or CyIgLambda in 100%; CD27– and CD81– in 94.1%; CD56+ in 67.6%; and CD117+ in 38.2%. Further, the authors found that high-risk cytogenetic abnormalities were more frequently associated with MRD-positive status (P = .039).

Among the 3 disease responses evaluated, MRD-positive status was highest in VGPR samples and lowest in sCR samples, at 53% and 25%, respectively. Further, the highest median (IQR) MRD levels correlated with samples demonstrating a VGPR (0.066% [0.009%-0.135%]) compared with those showing an sCR (0.009% [0.004%-0.046%]).

Progression-free survival (PFS) was lower in patients who had a VGPR compared with an sCR/CR (P < .001), in patients with MRD-positive vs MRD-negative disease (P = .796), and in patients with MRD-positive vs -negative disease who also had high-risk cytogenetics (P = .016). In addition, among patients with MRD-positive status who demonstrated an sCR/CR, PFS was inferior (P = .014). Multivariate analysis also showed 396% and 223% increased risks of inferior PFS in the presence of VGPR status (HR, 4.96; 95% CI, 1.47-16.72) and MRD positivity (HR, 3.23, 95% CI, 1.01-10.34).

Among those with 2 measures of MRD status, sustained MRD negativity “was observed only in patients with sustained sCR, and not in patients who showed CR or VGPR status at least once during follow-up (P = .002). No patient with sustained MRD-negative status had disease progression during follow-up.

The study authors highlight the sensitivity of their NGF-based MRD assessment, 10-5 (0.001%), in particular because “it remains difficult to implement high-sensitivity MRD tests in clinical laboratories.”

Despite noting several limitations on their findings—small patient population, short follow-up, heterogeneous MRD assessment timing—the authors concluded, “MRD can serve as a predictor of progression even in patients with high-risk cytogenetics. This study demonstrated the clinical utility of NGF-based MRD assessment in predicting disease progression in patients with MM in an actual clinical setting.”

They recommend a larger follow-up study to confirm their findings.

Reference

Kim H-Y, Yoo IY, Lim DJ, et al. Clinical utility of next-generation flow-based minimal residual disease assessment in patients with multiple myeloma. Ann Lab Med. 2022;42(5);558-565. doi:10.3343/alm.2022.42.5.558