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Role of Composite Measurable Residual Disease Assessment with PET-CT and flow cytometry in Multiple Myeloma patients undergoing Autologous Transplant

Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Bone marrow (BM) Measurable Residual Disease (MRD) assessments underestimate disease burden in multiple myeloma, as focal lesions can exist outside the marrow.Functional imaging, like positron emission tomography-computed tomography (PET-CT), offers valuable insights into residual disease beyond the marrow.Combining marrow flow cytometry (FCM) with PET-CT for a composite MRD (cMRD) assessment before and after autologous stem cell transplant (ASCT) is expected to provide prognostic information, particularly in settings where patients receive extended duration of anti-myeloma therapy prior to ASCT.Methods: In this retrospective cohort study, we evaluated the prognostic impact of cMRD in newly diagnosed multiple myeloma (NDMM) patients who underwent triplet/quadruplet-based induction followed by ASCT from January 2017 to June 2023.cMRD was assessed before ASCT and again around day 100 post-transplant.cMRD negativity was defined as undetectable residual clonal plasma cells (sensitivity 1×10 -5 ) on multi coloured FCM and PET-CT negativity per The International Myeloma Working Group criteria.Results: Among 106 patients undergoing ASCT, 82 had cMRD assessments before and on day 100 post-ASCT.Median pre-ASCT treatment duration was 11 months (interquartile range [IQR]: 4-18).At the pre-ASCT time point, sixty seven percent patients were bone marrow MRD negative (BM-MRD PRE-), while 38% were PET-CT negative (PET PRE-).Post-ASCT, these rates were 74% (BM-MRD POST-) and 49% (PET-CT POST-) respectively.At a median follow-up of 35 months (IQR: 23.5-58), median time to next treatment (TTNT) and overall survival (OS) were not reached.At three years, TTNT was significantly higher in patients who were cMRD-negative before ASCT compared to those who were cMRD-positive [91% (confidence interval (CI): 77-100) versus 67% (CI: 52-80); p=0.027].BM-MRD PRE-and PET PRE-were both independently associated with improved TTNT on univariate analysis [Hazard Ratio: 0.32 (0.14-0.74) and 0.45 (0.23-0.94) respectively].Post-ASCT cMRD status did not significantly impact TTNT [82% (CI: 68-96) versus 65% (CI: 51-69); p=0.116].Three-year TTNT rates were similar among patients with and without baseline high-risk cytogenetic abnormalities (HRCA) if they maintained sequential cMRD negativity.In multivariate analysis, the absence of HRCA, complete response before ASCT, cMRD PRE-, and sustained cMRD negativity at both time points were independent predictors of longer TTNT.Conclusions: Pre-ASCT cMRD assessment using both PET-CT and bone marrow FCM provides prognostic value in NDMM.This approach is particularly relevant in real-world settings where patients often receive prolonged induction therapy before ASCT.
Language: English
Subfield: Hematology
Field: Medicine
Open Access status: diamond
OpenAlex ID: W4412775337
FWCI: 1.308
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Cited by: 2
Related to: 10