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 in method reproducibility and sensitivity, prompting current authors to study its clinical utility.

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

The results were recently published in Annals of Laboratory Medicine, and the authors also note that patients with high-risk cytogenetic abnormalities can benefit from this technology, which they say is cost-effective and can produce rapid results. However, they added, “there is considerable heterogeneity in clinical application and interpretation of real-world results, which poses a challenge for sharing and accumulating experiences and data from diverse laboratories”.

Their investigation involved 90 patients (59, MRD negative; 31, MRD positive) from Samsung Medical Center in Korea, who provided 108 bone marrow samples and were prospectively recruited between February 2019 and October 2020. All patients had a suspected morphological remission after or during their MM Treatment. Electronic medical records provided data on protein electrophoresis, immunofixation, free light chain, and cytogenetics, and disease response was classified as strict complete remission (sCR), complete remission (CR ) and a 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 of those with only one light chain, 60.7% had the Kappa light chain type. Overall, the median detection limit (IQR) after 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%).

The abnormal plasma cells also presented the following aberrant markers: CD45–, CD19– and monoclonal CyIgKappa or CyIgLambda in 100% of cases; CD27– and CD81– in 94.1%; CD56+ in 67.6%; and CD117+ in 38.2%. Additionally, the authors found that high-risk cytogenetic abnormalities were more frequently associated with positive MRD status (P = 0.039).

Of the 3 disease responses assessed, MRD-positive status was highest in VGPR samples and lowest in sCR samples, at 53% and 25%, respectively. In addition, the highest median MRD levels (IQR) were correlated with samples demonstrating VGPR (0.066% [0.009%-0.135%]) compared to those with sCR (0.009% [0.004%-0.046%]).

Progression-free survival (PFS) was lower in patients who had VGPR compared to sCR/CR (P P = 0.796), and in patients with MRM-positive vs. negative disease who also had high-risk cytogenetics (P = 0.016). Additionally, among patients with positive MRD status who demonstrated sCR/CR, PFS was lower (P = 0.014). Multivariate analysis also showed 396% and 223% increased risks of lower 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 seen only in patients with sustained CRs, not in patients who showed CR or VGPR status at least once during follow-up (P = .002). No patient with sustained negative MRD status experienced 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 set up high-sensitivity MRD tests in clinical laboratories”.

Although they noted several limitations to their findings – small patient population, short follow-up, heterogeneous timing of MRD assessment – ​​the authors concluded that “MRD may 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 a real-life clinical setting.

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

Reference

Kim HY, 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

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