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IN MULTIPLE MYELOMA, T REGULATORY CELLS ARE SIGNIFICANTLY REDUCED AFTER TREATMENT WITH LENALIDOMIDE BUT NOT BORTEZOMIB AND CORRELATE WITH THE ACHIEVEMENT OF AT LEAST VERY GOOD PARTIAL RESPONSE
Author(s): ,
Christina Hadjiaggelidou
Affiliations:
Hematology Department, Theagenion Cancer Hospital, Thessaloniki, Greece,Thessaloniki,Greece
,
Evdokia Mandala
Affiliations:
Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki, Greece,Thessaloniki,Greece
,
Evangelos Terpos
Affiliations:
Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece,Athens,Greece
,
Dimitra Markala
Affiliations:
Hematology Department, Theagenion Cancer Hospital, Thessaloniki, Greece,Thessaloniki,Greece
,
Efthalia Yiannaki
Affiliations:
Hematology Department, Theagenion Cancer Hospital, Thessaloniki, Greece,Thessaloniki,Greece
,
Athanasios Papatheodorou
Affiliations:
Department of Medical Research, 251 General Air Force Hospital, Athens, Greece,Athens,Greece
,
George Ilonidis
Affiliations:
Fourth Department of Internal Medicine, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki, Greece,Thessaloniki,Greece
,
Sofia Vakalopoulou
Affiliations:
Second Propedeutic Department of Internal Medicine, Aristotle University of Thessaloniki, School of Medicine,Thessaloniki,Greece
Eirini Katodritou
Affiliations:
Hematology Department, Theagenion Cancer Hospital, Thessaloniki, Greece,Thessaloniki,Greece
(Abstract release date: 05/19/16) EHA Library. Hadjiaggelidou C. 06/09/16; 132863; E1314
Dr. Christina Hadjiaggelidou
Dr. Christina Hadjiaggelidou
Contributions
Abstract
Abstract: E1314

Type: Eposter Presentation

Background
Immune dysfunction is an important feature of Multiple Myeloma (MM) and has been associated with reduced survival. Studies have shown that T-regulatory cells (Tregs) implicated in immune surveillance are expanded in tumors, including MM. Data regarding alterations of Tregs during therapy with novel agents (NA) i.e. bortezomib and lenalidomide, are limited.

Aims
Our aim was to explore possible alterations of Tregs and lymphocyte subpopulations (T4, T8, B, NK, NK-like), as well as changes in the levels of cytokines related to Tregs function and MM biology (IL-6, IL-2, IL-17, TGF-β) during treatment with NA and to seek for correlations with disease characteristics and response parameters.

Methods
We evaluated 29 patients with symptomatic MM at diagnosis or relapse (M/F: 15/14, median age: 61 years, range: 39-77) and 20 healthy volunteers (HV). Eleven patients received bortezomib-dexamethasone (BD) (group A) and 18 patients received lenalidomide-dexamethasone (Rd) (group B). The median number of previous treatment lines was 2(0-3). The detection of Tregs and lymphocyte subpopulations was performed in peripheral blood samples using flow cytometry analysis. The cytokines were measured in serum samples using the enzyme-linked immunosorbent assay ELISA. The statistical analysis was performed with the appropriate methods; p<0.05 was considered statistically significant.

Results
In group A, no significant alterations of Tregs%, lymphocyte subpopulations or cytokines were observed during treatment. In group B, there was a significant reduction of Tregs % (p<0.001) and this was more profound in those who achieved ≥vgPR (p=0.04). No alterations regarding T subpopulations or cytokines were observed during treatment with NA in either group of patients. Patients had significantly higher median Tregs% compared to HV (p<0.001). There were no significant correlations between disease characteristics and Tregs in either group of patients. In the cox regression analysis, Tregs % did not correlate with progression-free survival (PFS).

Conclusion
Herein, we have demonstrated that Tregs% were significantly reduced after treatment with Rd especially in patients with ≥vgPR, suggesting a possible relation of immune surveillance with quality of response. However, PFS was not affected in the current study. Bortezomib-based treatment had no impact on Tregs number or function. Patients with myeloma had higher Tregs% compared to HV, confirming the implication of immune impairment in the biology of this disease. No relation between Tregs and disease characteristics was observed in this study nor between Tregs and relative cytokines, indicating that immune mechanisms underlying MM remain unexplored.

Session topic: E-poster
Abstract: E1314

Type: Eposter Presentation

Background
Immune dysfunction is an important feature of Multiple Myeloma (MM) and has been associated with reduced survival. Studies have shown that T-regulatory cells (Tregs) implicated in immune surveillance are expanded in tumors, including MM. Data regarding alterations of Tregs during therapy with novel agents (NA) i.e. bortezomib and lenalidomide, are limited.

Aims
Our aim was to explore possible alterations of Tregs and lymphocyte subpopulations (T4, T8, B, NK, NK-like), as well as changes in the levels of cytokines related to Tregs function and MM biology (IL-6, IL-2, IL-17, TGF-β) during treatment with NA and to seek for correlations with disease characteristics and response parameters.

Methods
We evaluated 29 patients with symptomatic MM at diagnosis or relapse (M/F: 15/14, median age: 61 years, range: 39-77) and 20 healthy volunteers (HV). Eleven patients received bortezomib-dexamethasone (BD) (group A) and 18 patients received lenalidomide-dexamethasone (Rd) (group B). The median number of previous treatment lines was 2(0-3). The detection of Tregs and lymphocyte subpopulations was performed in peripheral blood samples using flow cytometry analysis. The cytokines were measured in serum samples using the enzyme-linked immunosorbent assay ELISA. The statistical analysis was performed with the appropriate methods; p<0.05 was considered statistically significant.

Results
In group A, no significant alterations of Tregs%, lymphocyte subpopulations or cytokines were observed during treatment. In group B, there was a significant reduction of Tregs % (p<0.001) and this was more profound in those who achieved ≥vgPR (p=0.04). No alterations regarding T subpopulations or cytokines were observed during treatment with NA in either group of patients. Patients had significantly higher median Tregs% compared to HV (p<0.001). There were no significant correlations between disease characteristics and Tregs in either group of patients. In the cox regression analysis, Tregs % did not correlate with progression-free survival (PFS).

Conclusion
Herein, we have demonstrated that Tregs% were significantly reduced after treatment with Rd especially in patients with ≥vgPR, suggesting a possible relation of immune surveillance with quality of response. However, PFS was not affected in the current study. Bortezomib-based treatment had no impact on Tregs number or function. Patients with myeloma had higher Tregs% compared to HV, confirming the implication of immune impairment in the biology of this disease. No relation between Tregs and disease characteristics was observed in this study nor between Tregs and relative cytokines, indicating that immune mechanisms underlying MM remain unexplored.

Session topic: E-poster

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