(PA-192) Refining MRD Surveillance in Multiple Myeloma: Predictive Insights from Ultrasensitive Bone Marrow Analysis

Measurable residual disease (MRD) is a key prognostic marker in multiple myeloma (MM), guiding treatment, predicting relapse, and serving as a clinical trial endpoint. The widely adopted EuroFlow MRD method offers standardized protocols with a sensitivity of 10⁻⁵ to 10⁻⁶. However, higher sensitivity is still required for detecting low-level disease following potent immunotherapies, such as CAR T-cell therapy, bispecifics, and monoclonal antibodies, which can reduce tumor burden below conventional detection thresholds. To investigate whether an ultrasensitive MRD method using enriched CD138⁺ plasma cells more effectively identifies patients at risk of disease progression and relapse, we compared it with conventional EuroFlow MRD in bone marrow samples from 277 MM patients.

Methods:

Conventional MRD was performed following EuroFlow guidelines. For ultrasensitive MRD, CD138⁺ plasma cells were enriched using MACSprep™ CD138 MicroBeads with AutoMACS® system. Conventional MRD was analyzed using Infinicyt’s automated gating and identification tools, while ultrasensitive MRD was manually analyzed using Infinicyt software.

Results:

Among the 277 samples analyzed, conventional MRD detected positivity in 116 cases, all of which were confirmed by the ultrasensitive method. Of the 161 samples classified as MRD-negative by conventional assessment, 150 (93%) were also confirmed as negative by ultrasensitive MRD. However, 11 cases (7%) were reclassified as MRD-positive by the ultrasensitive method, with limits of detection (LODs) ranging from 0.000010 to 0.000036, and a median of 0.000019.

During follow-up, four of the 11 discordant cases later converted to MRD-positive by conventional assessment. Patient 1 became positive by conventional MRD 24 months after initial detection by the ultrasensitive method, while patients 2 and 3 converted within five months, and patient 4 at 18 months. Patients 1, 3, and 4 did not exhibit serological progression.

Patients 5, 7, 8, and 9 remained MRD-negative by conventional assessment throughout follow-up, spanning 3 - 15 months after ultrasensitive detection. They exhibited no signs of serological progression during subsequent evaluations. Follow-up data were unavailable for patient 11. Patients 2, 6, and 10 showed serological progression within two to five months after ultrasensitive assessment. Notably, patients 2 and 6 experienced relapse.

Conclusions:

Ultrasensitive MRD, with a detection threshold of up to 10⁻⁸, identified additional cases of residual disease and effectively anticipated disease progression and relapse. While conventional MRD, with a sensitivity of 10⁻⁶, remains a robust tool, these findings support incorporating ultrasensitive MRD into routine monitoring to enhance relapse prediction and guide timely therapeutic decisions, particularly for patients receiving high-efficacy immunotherapies.