High Level of Soluble Interleukin-2 Receptor in Serum Predicts Treatment Resistance and Poor Progression Free Survival in Multiple Myeloma

Background: 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 response and survival outcomes or not needs to be investigated in multiple myeloma (MM) patients.

Methods: The level of sIL-2R in serum was measured using enzyme-linked immunosorbent assay (ELISA) in 81 patients with newly diagnosed MM. 26 patients (32.1%) were treated with bortezomib-based regimens and 55 patients (67.9%) received old drugs-based regimens.

Results: The mean concentration of sIL-2R for myeloma patients was 8.51ng/ml, significantly higher than that of healthy controls (0.56ng/ml, p<0.0001). The best cutoff value for sIL-2R in predicting high risk for disease progression is 6.049ng/ml with an area under curve (AUC) of 0.665 (p = 0.013). 36 patients (44.4%) were classified as higher sIL-2R level group (>6.049ng/ml), and 45 patients (55.6%) as lower group (=<6.049ng/ml). The overall response rate (ORR) was 60.0% in lower sIL-2R level group, higher than that in higher level group (41.7%, p=0.156). The 3-year progression free survival (PFS) and overall survival (OS) rate was 16% and 64%, respectively. In a multivariate survival analysis including ECOG 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 correlated with significantly inferior PFS in patients treated with bortezomib-based regimens (p=0.004).

Conclusions: Serum sIL-2R level is a valuable biomarker for predicting treatment response and 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.