Abstract

Background: Multiple myeloma (MM) is a kind of hematological malignancy involved in monoclonal plasma cells. In most clinical guidelines autologous stem cell transplantation (ASCT) is considered as the standard of care for transplant-eligible patients (TEMM) as long as patients achieving partial response (PR). However, it is unclear that under the circumstance of not achieving complete response (CR) weather it would lead to the presence of neoplastic plasma cells in the stem cell collection (SCC) and then result in negative impact on survival prognosis. Aims: Here, we evaluated the effect of the minimal residual disease (MRD) of SCC in the TEMM. Methods: We analyzed retrospectively clinical data of 90 patients with MM undergoing ASCT between January 1, 2013 to June 1, 2021 and MRD evaluation of both bone marrow (BM) and SCC were carried out at the same time. MRD was evaluated by multiparameter flow cytometry (MFC) with 10-4-10-5 sensitivity. The best response was defined as the deepest response during the follow-up. Here we defined the time from ASCT to disease progression or death as modified progression-free survival (mPFS) and the time from ASCT to death as modified overall survival (mOS). Results: A total of 90 patients met the inclusion criteria. The median age is 54 (37-69) and 62.2% were males. There were 25 (27.8%) patients presenting high-risk cytogenetic abnormalities by FISH, defined as the presence of at least one of t (4;14), t (14;16) or del (17p). Before ASCT 36.7% of patients achieved MRD negativity in BM and 76.7% in SCC. After the comparison among MRD-positivity status with different sensitivity and numbers of detectable MRD neoplastic plasma cells, we found that the percentage of patients with MRD positivity in SCC was much less than that in BM no matter the sensitivity (P <0.001). Neither mPFS (P=0.861, median mPFS, 40.83m vs. 34.17m for negativity vs. positivity) nor mOS (P=0.747, median mOS, 67.02m vs. 58.86m for negativity vs. positivity) was affected by MRD status in SCC. According to MRD status they were divided into 4 groups, namely MRD negativity in BM and SCC (Group A, 34.4%), MRD positivity in BM but negativity in SCC (Group B, 22.2%), MRD positivity in BM and SCC (Group C, 41.1%) as well as MRD negativity in BM but positivity in SCC (Group D, 2.3%). Having taken the inaccuracy of biopsy into consideration we excluded Group D. The median follow-up of the cohort was 26.8 months (15.1-105.1m). Patients among the three groups experienced similar mPFS (P=0.403, median mPFS, 41.07m vs. 34.17m vs. 40.83m, for Group A, B and C, respectively) and similar mOS (P=0.933, median mOS, 67.02m vs. 58.86m vs. 58.61m for Group A, B and C, respectively). Achievement of CR with the presence of MRD negativity was associated with prolonged mPFS and mOS compared with MRD-positive CR or ≤VGPR (P<0.001, median mPFS, 55.88m vs. 23.03m vs. 27.10m, respectively; P=0.026, median mOS, 67.02 vs. 46.16m vs. 41.65m, respectively). Image:Summary/Conclusion: Our results demonstrated that neoplastic plasma cells in SCC have little impact on the survival prognosis in MM patients and it is sound to carry out ASCT when TEMM patients achieving PR. Also, MRD-negativity status can be considered more valuable on prognosis than CR.

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