The Value of PET/CT Combined with Next-Generation Flowcytometry in Minimal Residual Disease Detection and Prognostic Evaluation of Multiple Myeloma

Background: Minimal residual disease (MRD) plays an increasingly vital role in efficacy evaluation of multiple myeloma (MM), especially in the era of novel drugs. Currently, the mainstream MRD evaluation methods include next-generation sequencing (NGS), next-generation flowcytometry (NGF) and positron emission tomography/computed tomography (PET/CT). However, it remains to be solved which method holds the best sensitivity and specificity. Our research intends to compare the sensitivity between 11C-acatate, a novel PET tracer with the traditional one 18F-FDG, and meanwhile, explore the prognostic value of PET/CT and NGF. Methods: Our research included MM patients treated in our center between 2015.11 to 2021.11, who received standard medication and reached at least partial response. The patients were examined by 11C-acatate PET/CT (AC-PET), 18F-FDG PET/CT (FDG-PET) as well as Euroflow MRD assessment. Baseline characteristics including ISS stage, cytogenetic abnormalities, treatment and response were collected. Statistical analysis was conducted using SPSS 24.0, with Χ2 test or McNemar test for Categorical variables, and Kaplan-Meier analysis or COX regression model for survival analysis. Results: A total of 54 patients were included, with 42 patients received dual-tracer PET/CT, 10 patients received FDG-PET only and 2 patients received AC-PET only. 37 patients also underwent NGF MRD evaluation. The average age of all patients were 58.5 years, with ISS III patients accounting for 53.7% and cytogenetically high-risk patients accounting for 60.4%. 46.3% of patients completed autologous stem cell transplantation, and 90.7% of patients reached at least very good partial response. A total of 11 patients found minimal residual disease by PET/CT, with a sensitivity of 18.2% by AC-PET and 7.7% by FDG-PET. Although it appeared that AC-PET had superior sensitivity compared with FDG-PET, the difference was statistically insignificant (p=0.14). The paired test of dual-tracer PET/CT scan revealed a same result (p=0.13). In patients conducted NGF, the MRD positive rate was 40.5%. Paired test between NGF and PET/CT in these patients demonstrated that sensitivity of NGF was significantly higher than PET/CT (p=0.01). In terms of progression-free survival (PFS), single-factor analysis showed that ISS stage II or III, response not reaching stringent complete response and positive MRD by NGF were all adverse prognostic factor, with p value of 0.019, ＜0.001 and 0.008, respectively. Cox regression analysis further determined that positive MRD by PET/CT was also an independent prognostic factor. Conclusion: The novel tracer AC-PET is advantageous over traditional FDG-PET in sensitivity for MRD detection, although not statistically significant. However, the sensitivity NGF is still superior than either method of PET/CT. In terms of PFS, NGF and PET/CT are both independent prognostic factor.