Background Earlier studies have reported the impact of clonal plasma cell contamination within stem cell grafts as a negative prognostic factor. In this study we aimed to quantify circulating plasma cells (cPCs) by flow in apheresis products (gMRD) and compare with marrow (mMRD) and outcome. Methods All consecutive (September 2006 - July 2020) newly diagnosed transplant eligible multiple myeloma (MM) patients were included prospectively. In the sample drawn for HPSC quantification of the graft and bone marrow (only if response is ≥VGPR), the number of cPCs were quantified by Flow. As described earlier (Montero et al.) undetectable MRD is defined as absence of cPCs at a sensitivity of 10-4 (n=54) between 2006-2016 and 10-5 (n=37) after 2017. MRD assessment is similar in the graft and marrow. Statistical analysis was performed on merged data regardless of sensitivity of MRD assessment. Results were reported in the intention-to-treat (ITT) population for mMRD. Results Patients were given either Bortezomib based triplet without immunomodulatory drug (IMID) ((85.7%)) or with an IMID (17.6%) as induction. The median age was 62 years (range:37-75 years). 86 (94.5%) patients had cytogenetics by FISH at diagnosis, of which 14% had high risk. Extramedullary disease was detectable among 14.3%. Post-induction complete response (CR) was achieved in 28.6% (n=26). Following mobilization, gMRD was detectable in 57.1% of patients. CR rate among gMRD (+) vs. (-) patients were: 14/26 (26.9%) vs 12/39 (30.8%). Kappa coefficient (SE): -0.036, p:0.8) pointing to lack of correlation between gMRD and biochemical response. Undetectable mMRD was reached among 26.4%. Among the patients with CR mMRD detectable vs. undetectable: 15/67 (22.4%) vs 11/24 (45.8%) (SE: -0.151, p:0.03) points to a correlation between mMRD levels and biochemical response. Among 39/91 gMRD(-) patients, undetectable mMRD(-) was also observed in 46.2%. A statistically significant correlation between gMRD and mMRD (SE: 0.364, p Conclusions Our real-world triplet drug induction-based experience shows for the first time postinduction marrow and graft MRD to be correlated with each other and with PFS. A non-invasive cellular residual disease measurement within graft at either 10-4 or 10-5 level may be an additional end point for therapeutic efficacy.
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