High level of soluble interleukin-2 receptor in serum predicts treatment resistance and poor progression-free survival in multiple myeloma

Abstract

The IL-2/IL-2 receptor (IL-2R) system plays a central role in maintaining normal T cell immunity, and its disturbance is associated with several hematologic disorders. Studies have found in several types of lymphoma that abnormal amounts of soluble IL-2R (sIL-2R) may result in imbalance of the IL-2/IL-2R system and hence of the T cell immunoregulation. Whether the level of sIL-2R in blood could predict treatment outcomes or not needs to be investigated in multiple myeloma (MM) patients. The level of sIL-2R in serum was measured using enzyme-linked immunosorbent assay (ELISA) in 81 patients with newly diagnosed MM. Twenty-six patients (32.1%) were treated with bortezomib-based regimens and 55patients (67.9%) received old drugs-based regimens. The mean concentration of sIL-2R for myeloma patients was 8.51 ng/ml, significantly higher than that of healthy controls (0.56 ng/ml, p < 0.0001). The best cutoff value for sIL-2R in predicting high risk for disease progression is 6.049 ng/ml with an area under curve (AUC) of 0.665 (p = 0.013). Thirty-six patients (44.4%) were classified as higher sIL-2R level group (> 6.049 ng/ml), and 45 patients (55.6%) as lower group (≤ 6.049 ng/ml). The overall response rate (ORR) was 60.0% in lower sIL-2R level group, and 41.7% in higher level group (p = 0.156). The median progression-free survival (PFS) and overall survival (OS) was 12 months (range, 2.0-65 months) and 20 months (range, 2.0-118 months), respectively. In a multivariate survival analysis, including Eastern Cooperative Oncology Group performance status score, treatment response, and sIL-2R level, it was found that all these three parameters were significantly independent prognostic factors for PFS (p = 0.032, 0.016, and 0.043, respectively), but none factors maintained their value in predicting OS. Subgroup analysis revealed that high level of sIL-2R is correlated with significantly inferior PFS in patients treated with bortezomib-based regimens (p = 0.004). Serum sIL-2R level is an independent prognostic factor for PFS, indicating novel drugs targeting the imbalance of IL-2/IL-2R system may be a promising strategy in MM.

Serum sCD25 Protein as a Predictor of Lack of Long-Term Benefits from Immunotherapy in Non-Small Cell Lung Cancer: A Pilot Study

“…To our best knowledge, our study is the first one indicating sCD25 as a useful marker that could be easily measured and indicate patients with NSCLC who would not benefit from immunotherapy with ATEZO or PEMBRO. Worth noting is that we obtained a similar cut-off for baseline sCD25 (5.99 ng/mL) as Cabrera et al [25] (5.80 ng/mL) and Wang et al [22] (6.05 ng/mL), who found correlations between the elevated sCD25 levels and shorter OS or PFS in other types of cancers.…”

“…Data from the literature show that while the sCD25 protein level is not affected by gender in healthy individuals [45,46], it may be disease-specific [42]. Although some authors reported that serum sCD25 increased with age [27,46,47], others obtained contradictory results [22,42]. We observed no difference in baseline sCD25 between older and younger individuals.…”

“…The elevated levels of serum sCD25 (sIL-2R) have been linked with poor outcomes in various blood [22,23] and solid cancers [24][25][26][27], including NSCLC [28][29][30]. Cabrera and colleagues [25,31] observed the elevated levels of sCD25 in hepatocellular carcinoma and postulated sCD25 as a mediator of T-cell suppression and tumor progression.…”

Immunological Features and Cytokine Regulation in Plasma Cell Neoplasms

“…У пациентов с ММ с прогрессией заболевания и рефрактерностью к проводимой химиотерапии на первичном этапе диагностики выявлено значимое превышение уровней IL-2 (p=0,001), IL-6 (p=0,006), TNF (p=0,000), которые, по литературным данным, коррелируют с активностью процесса и тяжестью заболевания [17,18]. ЗАКЛЮЧЕНИЕ Данные о прогностических факторах при ПН могут являться основополагающими в вопросах назначения специфической терапии и должны определять направление дальнейших исследований.…”

Predictive Role of Immune Profiling for Survival of Multiple Myeloma Patients

“…Multivariate survival analysis indicates that sIL-2R levels are an independent prognostic factor for PFS. Furthermore, based on subgroup analysis results, high levels of sIL-2R are associated with poor PFS in MM patients (29). IL-2 can not only stimulate NK and T cell growth and enhance cytolytic action strongly, but also sensitizes T cells to activation-induced cell death and is required for Treg cells to reduce persistent immune responses (82).…”