According to research published in Blood Advances, minimal residual disease (MRD) conversion occurred in 39% of patients with multiple myeloma (MM) who achieved bone marrow (BM) MRD negativity after autologous stem cell transplantation (ASCT) with maintenance combination therapy and reliably predicted future relapse.

The investigators aimed to evaluate the clinical implications of the loss of a previously attained state of BM MRD negativity and imaging-based negativity in patients with MM following ASCT and maintenance combination therapy with an immunomodulatory agent and a proteasome inhibitor.

The researchers conducted comprehensive longitudinal response assessment with serial integration of positron emission tomography-computed tomography or MRI studies and BM MRD testing, regardless of disease status, of participating patients. They evaluated BM MRD using next-generation flow cytometry (sensitivity, 10-5 cells) at 3- to 6-month intervals.

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A total of 568 patients (59.2% male and 40.8% female) who achieved both BM MRD negativity and imaging-based negativity participated in the study. Patients had a median age of 58 years (range, 29-80) and were 83.9% Caucasian, 13.9% Hispanic, 13.8% African American, 1.6% Asian, and 0.7% Native American.

At a median follow-up duration of 9.9 years from diagnosis (range, 0.4-30.9), 61% of patients maintained MRD negativity, while 39% experienced MRD conversion at a median of 6.3 years (range, 1.4-25) from the start of treatment. Patients were more likely to lose MRD negativity within the first 5 years after treatment (89%) compared with 5 to 10 (38%), >10 (20%), and >15 years (16%).Patients who experienced MRD conversion more frequently had any abnormal metaphase cytogenetic abnormality at diagnosis than patients who maintained MRD negativity (95% vs 84%; P =.001).

Patients who experienced MRD conversion had a significantly increased risk of clinical relapse than those who maintained MRD negativity (73% vs 4%; relative risk, 3.5; P <.0001). MRD conversion preceded biochemical relapse at a median time of 0.5 years (range, 0-2.7) and clinical relapse by a median time of 1.0 years (range, 0-4.9). At a median follow-up duration of 9.3 years (range, 2.2-21.2), 27% of patients who experienced MRD conversion had not yet experienced clinical relapse; most of these patients (65%) had GEP70 subtypes CD2 and HY.

Landmark analyses of 3 years from first ASCT revealed patients with MRD conversion  had an inferior overall and progression-free survival compared with patients with sustained MRD negativity (OS: hazard ratio [HR], 5.7; 95% CI, 6.3-63.0; P <.0001; PFS: HR, 4.5; 95% CI, 4.3-33.7; P <.0001).

“MRD conversion correctly predicted relapse in 70%, demonstrating the utility of serial BM MRD assessment to complement standard laboratory and imaging to make informed salvage therapy decisions,” concluded the researchers.

Limitations of the study included MRD assessment at various time points from upfront ASCT and the heterogeneous therapy received by patients.


Mohan M, Kendrick S, Szabo A, et al. Clinical implications of loss of bone marrow minimal residual disease negativity in multiple myeloma. Blood Adv. 2022;6(3):808-817. doi:10.1182/bloodadvances.2021005822