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Minimal Clonal Plasma Cell Contamination of Peripheral Stem Cell Grafts Has an Adverse Prognostic Impact in Patients
Yang Liu1, Danyang Shao1, Yingjun Chang1
1Department of Hematology, Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Center of Hematologic Disease, Beijing, China.
Introduction:
The significance of autografts' contamination by clonal plasma cells on clinical outcome in newly diagnosed multiple myeloma (NDMM) remains controversial.
Methods:
We retrospectively reviewed the clinical and laboratory data of NDMM patients who underwent autologous stem cell transplantation (ASCT) and had received graft minimal residual disease (gMRD) examination by multi-color flow cytometry.
Results:
From January 2011 to December 2022, 250 NDMM patients with complete cytogenetic information, gMRD information, and who received ASCT as consolidation were enrolled. Multi-flow cytometry can achieve a median detection sensitivity of 0.004%, and gMRD positivity was 12.4% at a median level of 0.0160% (interquartile range, 0.0049%, 0.05394%). Its presence was correlated with response to induction treatment, with percentages of 2.65%, 12.94%, 28.89%, and 57.14% of patients achieving complete response, very good partial response, partial response, and minimal response/stable disease, respectively. gMRD (+) patients had a higher risk of not achieving bone marrow MRD negativity post-ASCT. After a median follow-up of 33.5 months for the whole cohort, patients in the gMRD (+) group had significantly worse progression-free survival (PFS) than those in the gMRD (-) group did (34.8 vs. 65.0 months, p = 0.001). Multivariable analysis revealed that gMRD (-) was independently predictive of better PFS (hazard ratio 0.464, 95% confidence interval: 0.274-0.785, p = 0.004). We found the significance of gMRD on PFS was in high-risk subgroups and in patients who achieved ≤ partial response prior to ASCT.
Conclusions:
In conclusion, gMRD (+) was an independent risk factor for inferior progression-free survival, with the impact primarily affecting high-risk groups and patients who achieved ≤ partial response before ASCT.
Insights
Graft minimal residual disease (gMRD) positivity in autografts is an independent risk factor for worse progression-free survival in newly diagnosed multiple myeloma patients. This impact is most significant in high-risk patients and those with suboptimal response before transplantation.
Area of Science:
- Hematology
- Oncology
- Clinical Research
Background:
- The prognostic value of clonal plasma cell contamination in autografts for newly diagnosed multiple myeloma (NDMM) patients undergoing autologous stem cell transplantation (ASCT) is debated.
- Assessing graft minimal residual disease (gMRD) is crucial for understanding treatment efficacy and patient outcomes.
Purpose of the Study:
- To investigate the association between gMRD positivity and clinical outcomes, specifically progression-free survival (PFS), in NDMM patients post-ASCT.
- To identify subgroups of patients where gMRD status has the most significant impact on PFS.
Main Methods:
- Retrospective analysis of 250 NDMM patients who underwent ASCT and gMRD examination via multi-color flow cytometry.
- gMRD detection sensitivity of 0.004% was achieved, with gMRD positivity identified in 12.4% of patients.
- Clinical and laboratory data, including response to induction treatment and post-ASCT MRD status, were analyzed.
Main Results:
- gMRD positivity was associated with poorer response to induction therapy and a higher risk of not achieving bone marrow MRD negativity post-ASCT.
- Patients with gMRD positivity had significantly shorter PFS (34.8 months) compared to gMRD-negative patients (65.0 months; p=0.001).
- Multivariable analysis confirmed gMRD negativity as an independent predictor of better PFS (HR 0.464, p=0.004), particularly in high-risk subgroups and those with ≤ partial response pre-ASCT.
Conclusions:
- gMRD positivity is an independent risk factor for inferior PFS in NDMM patients treated with ASCT.
- The negative impact of gMRD is most pronounced in high-risk patient populations and those achieving only a partial response or less prior to transplantation.
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