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

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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.

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Acknowledgments

We appreciate the support from Dr. Hao Chen, who helped us measure the level of sIL-2R in this study. This work received grant support from the National Natural Science Foundation of China (contract/grant number: 81400159) and Pearl River Nova Program of Guangzhou (contract/grant number: 201710010161).

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Author notes

  1. Liang Wang, Jing-hua Wang, and Wen-jian Liu contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, ZhuJiang Hospital of Southern Medical University, Guangzhou, 510280, Guangdong, People’s Republic of China

    Liang Wang

  2. Department of Hematology, Guangdong General Hospital, Guangzhou, 510060, Guangdong, People’s Republic of China

    Jing-hua Wang

  3. Department of Hematologic Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, 510060, Guangdong, People’s Republic of China

    Wen-jian Liu, Wei-da Wang, Hua Wang, Xiao-qin Chen, Qi-rong Geng, Yue Lu & Zhong-jun Xia

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  1. Liang Wang
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Contributions

LW conceived and designed the experiments. LW, JHW, WJL, WDW, and HW performed the experiments. LW and WDW analyzed the data. YL, ZJX, XQC, and QRG contributed to reagents/materials/analysis tools. JHW, LW, WJL, WDW, and HW wrote the paper. All authors have read and approved the final version of this manuscript.

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Correspondence to Liang Wang.

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The authors declare that they have no conflicts of interest relevant to the manuscript submission.

Ethics statement

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this retrospective study, formal consent is not required.

Informed consent statement

Informed consent was obtained from all individual participants included in the study.

Electronic supplementary material

Supplementary Figure 1

Level of sIL-2R in three representative patients at different timepoints. The level of sIL-2R significantly decreased when CR was achieved and increased at relapse. (JPEG 90 kb)

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Wang, L., Wang, Jh., Liu, Wj. et al. High level of soluble interleukin-2 receptor in serum predicts treatment resistance and poor progression-free survival in multiple myeloma. Ann Hematol 96, 2079–2088 (2017). https://doi.org/10.1007/s00277-017-3125-4

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  • DOI: https://doi.org/10.1007/s00277-017-3125-4

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