Predictive Values of PET/CT in Combination With Regulatory B Cells for Therapeutic Response and Survival in Contemporary Patients With Newly Diagnosed Multiple Myeloma

Abstract

To assess patients with multiple myeloma (MM), the whole-body positron-emission tomography/computed tomography (PET/CT) occupies a pivotal position for diagnostic stratification, response evaluation, and survival prediction, while important limitations are recognized as incapable of representing tumor microenvironment. Regulatory B cells (Bregs) have been reported to have an inhibitory immune function, contributing to bone marrow (BM)-immunosuppressive microenvironment for MM. Therefore, to investigate the role of PET/CT in combination with Bregs’ ratios to predict therapeutic response and survival, we sequentially enrolled 120 patients with newly diagnosed MM (NDMM) who were treated with novel agents in our center, while conventional PET/CT parameters including maximum standard uptake value (SUVmax), ratios of BM-derived Bregs within CD19+ B cells, and patients’ clinical characteristics were collected. After a median follow-up of 28.20 months (range 7.00–46.93 months), SUVmax > 4.2 at onset, accounting for 53.2% of NDMM, was uncovered to predict inferior progression-free survival (PFS) as well as overall survival (OS). With regard to the ratios of BM-derived Bregs within CD19+ B cells, the cohort with the Bregs’ proportions lower than 10%, accounting for 46.2%, exerted poorer OS. Additionally, the patients with both SUVmax > 4.2 and Bregs’ ratios < 10%, accounting for 31.7%, yielded compromised therapeutic response and long-term survival. Collectively, this study may draw attention on the prognostic value of combination of PET/CT and Bregs’ ratios when clinical decisions are made for MM in the era of novel agents.

A stratified therapeutic model incorporated with studies on regulatory B cells for elderly patients with newly diagnosed multiple myeloma

“…This study also confirmed that for elderly patients with MM, the proportion of BM‐derived Bregs is related to the OS, while the proportions of Bregs and SUVmax were significantly associated with OS but not PFS, which was similar to our previous studies 19 . It may indicate that Bregs may negatively affect survival independent of tumor progression, and OS was valued as a more critical cancer trial outcome compared with PFS 35 .…”

“…This study also confirmed that for elderly patients with MM, the proportion of BM‐derived Bregs is related to the OS, while the proportions of Bregs and SUVmax were significantly associated with OS but not PFS, which was similar to our previous studies. 19 It may indicate that Bregs may negatively affect survival independent of tumor progression, and OS was valued as a more critical cancer trial outcome compared with PFS. 35 Bregs, a population of suppressor B cells, were initially described in autoimmune disease and much progress has been made to characterize their phenotype and function in the tumor microenvironment over the past decade.…”

“… 15 Bregs' ratios were also found to be positively correlated with the preserved B cells in MM, while the higher percentages of Bregs may be associated with better prognosis. 19 Differing from our previous reports on the whole NDMM population taking no account of age and transplantation implementation, the study further focuses on the elder subpopulation of NDMM, which is probably ineligible for transplantation. Additionally, there are great variabilities among the enrollment time, follow‐up time, and both inclusion and exclusion criteria, showing minimal overlap across the research databases.…”

“…The operation of FDG‐PET/CT scan was carried out following the guidelines of the European Association of Nuclear Medicine 18 . In order to standardize the analysis of the PET/CT scan results, we adopted the criteria from the works reported by Bologna and Udine, which were briefly described in our previous work 19 . In this study, SUVmax >4.2 was adopted as a demarcation indicator for unfavorable survival, which has also been endorsed in previous studies 20‐22 …”

The yin–yang effects of immunity: From monoclonal gammopathy of undetermined significance to multiple myeloma

“…While the percentage of CD19+CD24 high CD38 high Bregs in MM patients decreased after treatment with daratumumab ( 113 ). Furthermore, the Breg combination with PET/CT can predict the therapeutic response and survival in contemporary patients with NDMM ( 114 ). Thus, Bregs also display the yin and yang effect in MM ( Figure 2 , Table 1 ).…”