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Arch Hellen Med, 33(4), July-August 2016, 519-526


T-regulatory cells are reduced after treatment with lenalidomide, but not bortezomib, in multiple myeloma

C. Hadjiaggelidou,1 E. Mandala,2 E. Terpos,1,3 D. Markala,1 E. Yiannaki,1 A. Papatheodorou,3
G. Ilonidis,2 V. Garipidou,4 G. Kaiafa,5 V. Perifanis,5 S. Vakalopoulou,4 A. Garifalos,2 E. Katodritou1,6

1Greek Myeloma Working Group,
2Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki,
3Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens,
4Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki,
5First Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, Thessaloniki,
6Department of Hematology, "Theagenion" Cancer Hospital, Thessaloniki, Greece

OBJECTIVE Τo explore possible alterations of Τ-regulatory cells (Tregs) and lymphocyte subpopulations (T4, T8, B, NK, NKL), and changes in the levels of cytokines related to the function of Tregs and the biological parameters of multiple myeloma (MM) (IL-6, IL-2, IL-17, TGF-β) during treatment with novel agents (NA), and their correlation with disease characteristics and response parameters.

METHOD The study was conducted on 29 patients with symptomatic MM at diagnosis or during relapse (male/female: 15/14, median age: 61 years, range: 39–77 years). Of the NA, 11 patients were administered bortezomib-dexamethasone (BD) (group A) and 18 lenalidomide-dexamethasone (Rd) (group B). The patients had received 0–3 previous treatment lines (median 2). Tregs and lymphocyte subpopulations were detected in peripheral blood samples using polyparametric flow cytometry analysis and appropriate isotypic controls from healthy subjects. Cytokines were measured in serum samples using the enzyme-linked immunosorbent assay ELISA. Statistical analysis was performed using appropriate methods and p<0.05 was considered statistically significant.

RESULTS In group A, no significant alteration in Tregs%, lymphocyte subpopulations or cytokines were observed during treatment. In group B, there was a significant reduction in Tregs% (p<0.001) which was more marked in patients who achieved at least a very good partial response to treatment (≥vgPR) (p=0.04). No alteration in lymphocyte subpopulations or cytokines was observed during treatment with NA in either group of patients. Patients had a significantly higher median Tregs% than healthy control subjects (HV) (p<0.001). No significant correlation was detected between disease characteristics and Tregs in either group of patients. In Cox regression analysis, Tregs% was not correlated with progression free survival (PFS).

CONCLUSIONS Tregs% was significantly reduced after treatment with Rd, especially in patients with ≥vgPR, suggesting a possible relationship between the immune phenomena of MM and the quality of response, although the PFS was not affected in this study. Bortezomib-based treatment had no impact on Tregs%. Patients with MM had higher Tregs% than HV, confirming the implication of immune impairment in the biology of this disease. No relationship between Tregs and disease characteristics was observed, nor between Tregs and relevant cytokines, indicating that the immune mechanisms underlying MM need to be explored.

Key words: Bortezomib, Lenalidomide, Multiple myeloma, T-regulatory cells (Tregs).

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