New Minimal Residual Disease Assessment Could Detect Disease Progression Earlier in MM

Flow–minimal residual disease (MRD) assessment in patients with multiple myeloma (MM) was found to be a sensitive and appropriate tool for longitudinal monitoring of MRD, with the potential for detection of early clonal expansion months prior to biochemical and clinical progression, according to a substudy.

The substudy, published in BMC Cancer, offered insight into how Flow-MRD can be used for deeper response evaluation in patients with MM, and the investigators suggested that the tool should be tested in future clinical trials for possible early intervention opportunities.

“Our data confirm that flow-MRD is a sensitive tool for response evaluation and subsequent patient monitoring….This offers the opportunity for early intervention and such strategies should be tested in clinical trials,” the investigators wrote.

Although advances such as stem cell transplants, proteasome inhibitors, immune-modulators, and monoclonal antibodies have contributed to significant improvements in treatment response and clinical outcomes in patients with MM, the majority of patients continue to develop residual disease.

Standardization of MRD testing in MM and defining the role that it can play in guiding treatment decisions remain unclear. The investigators of the present analysis conducted the NMSG MRD substudy as a portion of the ENM02/HO95 trial, which comprised data from 23 sites from the Nordic countries between March 1, 2012, and March 21, 2014.

Patients who underwent bone marrow aspiration for response assessment before beginning maintenance treatment were eligible for enrollment. In total, 136 patients between ages 18 and 64 years were registered in the substudy. Bone marrow aspirate samples were sent for 53 patients, and 15 patients with confirmed clinical response status and an adequate bone marrow sample were included in the first flow response assessment analysis.

Longitudinal flow-MRD analyses were conducted to determine the potential of flow-MRD monitoring on the risk of disease progression and to evaluate it. Patients had to achieve complete response over the study period while receiving treatment for data inclusion. Among the 53 patients, 34 achieved complete response, of whom 20 demonstrated at least 3 flow-MRD assessment points with adequate bone marrow samples that were analyzed. Of those 20 patients, 13 displayed sustained flow-MRD negativity upon acquisition accompanied by normal values and they all remained clinical progression free within the 6-year observation period.

Six patient experienced increased levels of MRD in bone marrow. Flow-MRD positivity was observed a median of 12.6 months before clinical progression was recorded and 5.5 months before biochemical parameters became abnormal. The mean malignant plasma cell doubling time for these patients was 1.8 months (95% CI, 1.4-2.3 months).

The study had some limitations, including that invasive bone marrow sampling routine monitoring of MRD may not account for spatial heterogeneity and the patchy nature of MM, which could have caused false-negative results. Additionally, undetectable MRD in bone marrow may hide extramedullary disease and bone marrows are invasive procedures.

“This study emphasises that flow-MRD assessment is a sensitive and appropriate tool for deeper response evaluation in MM patients beyond [complete response], and for longitudinal monitoring of MRD with potential detection of early clonal expansion several months prior to biochemical and clinical progression,” noted the investigators.

Reference

Schmitz A, Brøndum RF, Johnsen HE, et al. Longitudinal minimal residual disease assessment in multiple myeloma patients in complete remission – results from the NMSG flow-MRD substudy within the EMN02/HO95 MM trial. BMC Cancer. 2022;22:147. doi:10.1186/s12885-022-09184-1