Serum Interleukin-10 Levels in Patients Affected With Multiple-Myeloma - Correlation With the Monoclonal Component and Disease Progression

Ameglio, F.; Alvino, S; Trento, Elisabetta; Marcucci, M; Pimpinelli, Fulvia; Tong, Alex W.; Gandolfo, G.M.; Greco, C.

doi:10.3892/ijo.6.6.1189

Cited by 2 publications

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“…In clinical assessment of response to pneumococcal vaccines containing multiple serotypes (typically [13][14][15][16][17][18][19][20][21][22][23] in healthy individuals a response is considered normal when inducing protective levels against two-thirds of serotypes (8/12). The healthy controls in this study were UK blood donors under the age of 65 years and thus unlikely to have ever been vaccinated against pneumococcus.…”

Section: Chapter 3 Resultsmentioning

confidence: 99%

“…14,15 Furthermore, the level of IL-10 has been shown to be elevated in MM patients, and correlates significantly with disease progression. 16 Therefore, IL-10 may be implicated in both susceptibility to infection and active MM and be a therapeutic target. These biomarkers of immune competence have not been studied in the context of antibiotic prophylaxis and infection in myeloma.…”

Section: Neutrophil Biomarkersmentioning

confidence: 99%

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Stratifying risk of infection and response to therapy in patients with myeloma: a prognostic study

et al. 2020

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Background Multiple myeloma is a cancer of plasma cells that is associated with severe immunodeficiency and increased numbers of bacterial infections. The Tackling Early Morbidity and Mortality in Myeloma (TEAMM) trial assessed the use of prophylactic levofloxacin in newly diagnosed multiple myeloma patients. Interactions between multiple myeloma disease activity, immunity and infection are central to the TEAMM trial. Active multiple myeloma suppresses immunity and infections delay administration of anti-multiple myeloma therapy. Furthermore, infection-derived inflammation nurtures multiple myeloma activity and resistance to anti-multiple myeloma therapy. Objectives The aim of this study was to measure biomarkers of (1) immune competence to develop risk stratification of patients for infection to personalise the decision to prescribe antibiotics, (2) myeloma activity to sensitively measure speed and depth of myeloma response and (3) inflammation to identify patients who may be at risk of poor treatment responses. Method Serum samples were collected from 977 TEAMM trial patients (aged 35–90 years) at randomisation, then every 4 weeks for 16 weeks and again at 1 year. Biomarker levels were compared with samples from healthy controls. Multiplex Luminex® assays (R&D Systems, Minneapolis, MN, USA) and enzyme-linked immunosorbent assays were used for the analysis of biomarkers and anti-viral antibodies were measured by a haemagglutination assay. Results At baseline, levels of both polyclonal immunoglobulins and anti-bacterial antibodies were below the normal range in most TEAMM trial patients. This immunoparesis was much more severe for antibodies against specific bacterial targets than for total immunoglobulin levels. Levels of anti-bacterial antibodies were below the threshold of protection for 18 of the 19 bacterial antigens tested. More patients aged < 65 years were protected against meningococcal serotypes, Haemophilus influenza type b and tetanus, whereas more patients aged ≥ 65 years were protected against pneumococcal serotypes but there was good protection in only 6% of the TEAMM trial patients. Higher levels of polyclonal immunoglobulins, but not specific anti-bacterial antibodies, were found to be associated with a lower risk of infection and a longer survival. At presentation, levels of neutrophil elastase, calprotectin and interleukin 10 were elevated in TEAMM trial patients, compared with healthy controls. Interleukin 10 levels were related to infection during the trial: patients with interleukin 10 levels ≥ 10 pg/ml had a greater risk of infection than patients with interleukin 10 levels < 10 pg/ml. Levels of soluble CD138 were elevated in 72% of TEAMM trial patients and were decreased in response to therapy, with a complete response seen in 40% of TEAMM trial patients by 16 weeks. Of the 76 TEAMM trial patients achieving a free light chain complete response at 16 weeks, only 30% had a soluble CD138 complete response. Overall, responses in the levels of soluble CD138 did not correlate with free light chain and myeloma monoclonal protein (also known as m-protein) responses, consistent with the fact that soluble CD138 responses reflect a separate aspect of disease activity and clonal size. Levels of procalcitonin were elevated in only 50% of patients who had febrile episodes during the TEAMM trial. Although levels of interleukins 6 and 8 at presentation were lower than in a heathy cohort of patients, lower levels of interleukin 6 were identified at baseline in poor responders than in good responders, and in patients who had febrile and non-febrile infections during the trial than in patients who had only non-febrile episodes. Conclusion Information from this Efficacy and Mechanism Evaluation project can help inform risk stratification and patient identification strategies to be responsive to individual patient needs. Monitoring levels of free light chains and soluble CD138 can help identify non-responders early and monitoring interleukin 10 levels can help stratify patients for risk of infection. Furthermore, immunisation in remission should be tested. Limitations The TEAMM trial administered prophylactic antibiotics or placebo for 12 weeks from a new diagnosis of myeloma. Patients were monitored for infections for 16 weeks post diagnosis, with a final set of clinical data gathered at 1 year. Infection data and efficacy of prophylactic antibiotics are available for only the first 16 weeks and survival for the first 52 weeks. This limits long-term data, particularly for progression-free and overall survival. Future work The TEAMM 2 trial (in preparation) will explore the benefit of prophylactic antibiotics up to 12 months following diagnosis and will explore infection risk post therapy and during remission. Furthermore, some of the key findings will be applied to investigate biomarkers in samples from other UK myeloma trials in which long-term outcome data are available. Trial registration Current Controlled Trials ISRCTN51731976. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership, and will be published in full in Efficacy and Mechanism Evaluation; Vol. 7, No. 10. See the NIHR Journals Library website for further project information.

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Section: Chapter 3 Resultsmentioning

confidence: 99%

Section: Neutrophil Biomarkersmentioning

confidence: 99%

Stratifying risk of infection and response to therapy in patients with myeloma: a prognostic study

et al. 2020

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“…IL-10 is a key anti-inflammatory mediator that protects the host from pathogen and microbiota overreaction, while playing an active role in other environments such as sterile wound healing, autoimmunity, and cancer ( 124 ). Serum IL-10 levels were obviously increased in MGUS patients compared to HDs and lower than those observed in MM patients ( 125 ). Wang et al.…”

Section: The Yin and Yang Effects Of Non-cellular Components Associat...mentioning

confidence: 99%

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

Liu

et al. 2022

Front. Immunol.

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Multiple myeloma (MM) is the third most common malignant neoplasm of the hematological system. It often develops from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) precursor states. In this process, the immune microenvironment interacts with the MM cells to exert yin and yang effects, promoting tumor progression on the one hand and inhibiting it on the other. Despite significant therapeutic advances, MM remains incurable, and the main reason for this may be related to the complex and variable immune microenvironment. Therefore, it is crucial to investigate the dynamic relationship between the immune microenvironment and tumors, to elucidate the molecular mechanisms of different factors in the microenvironment, and to develop novel therapeutic agents targeting the immune microenvironment of MM. In this paper, we review the latest research progress and describe the dual influences of the immune microenvironment on the development and progression of MM from the perspective of immune cells and molecules.

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Serum Interleukin-10 Levels in Patients Affected With Multiple-Myeloma - Correlation With the Monoclonal Component and Disease Progression

Cited by 2 publications

References 0 publications

Stratifying risk of infection and response to therapy in patients with myeloma: a prognostic study

Stratifying risk of infection and response to therapy in patients with myeloma: a prognostic study

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

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