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THE PROGNOSTIC ROLE OF INDOLEAMINE 2,3-DIOXYGENASE EXPRESSION IN HODGKIN’S LYMPHOMA.
Author(s):
T. Skrypets
,
T. Skrypets
Affiliations:
Oncohematology,National Cancer Institute,Kiev,Ukraine
O. Novosad
,
O. Novosad
Affiliations:
Oncohematology,National Cancer Institute,Kiev,Ukraine
N. Svergun
,
N. Svergun
Affiliations:
Experimental Oncology,National Cancer Institute,Kiev,Ukraine
O. Skachkova
,
O. Skachkova
Affiliations:
Experimental Oncology,National Cancer Institute,Kiev,Ukraine
O. Gorbach
,
O. Gorbach
Affiliations:
Experimental Oncology,National Cancer Institute,Kiev,Ukraine
V. Sokolov
,
V. Sokolov
Affiliations:
Thoracic surgery,Clinical Hospital №18,Kiev,Ukraine
N. Khranovska
,
N. Khranovska
Affiliations:
Experimental Oncology,National Cancer Institute,Kiev,Ukraine
I. Kryachok
I. Kryachok
Affiliations:
Oncohematology,National Cancer Institute,Kiev,Ukraine
(Abstract release date: 05/18/17) EHA Library. Skrypets T. 05/18/17; 182783; PB2069
Tetiana Skrypets
Tetiana Skrypets
Contributions
PDF Abstract
Abstract

Abstract: PB2069

Type: Publication Only

Background
Indoleamine 2,3-dioxygenase (IDO) is an inducible enzyme that catalyzes the initial and rate-limiting step in tryptophan along the kynurenine pathway. IDO is a key factor maintaining immune tolerance and expression and it correlates with poor clinical outcome in different types of cancer and hematological malignancies. It also plays a role in a lot of pathophysiological processes, such as antitumor and antimicrobial defense. IDO causes immunosuppression in the tumor microenvironment by tryptophan breakdown. Although, only several reviews have been made to evaluate IDO prognostic value and its expression value in hematological malignancies.

Aims
The aim of the study was to assess the impact of the IDO expression on clinical outcome in patients with Hodgkin’s lymphoma (HL).

Methods

A total number of 35 patients with HL were included in the group (10 males and 25 females; median age: 17-60 years, range: 38.5 years). Early stages (I-II) and advanced stages (III-IV) were diagnosed in 48.5% (17/35) and 51.4% (18/35) of patients, respectively. B-symptoms had 37.1% (13/35) of patients at the time of diagnosis. Patients were treated with ABVD or BEACOPP (14/esc) and radiation therapy. The mRNA expression level of IDO was measured in pre-treatment tumor tissue specimens from HL patients using real-time qPCR analysis.

Results

For 35 patients with HL, the overall response rate after the first-line therapy was 88.6 % (31/35). Progression of the disease during the therapy was observed in 11,4% of patients (4/35). Among the patients, who achieved a remission, 9 had relapses.
In our study, only 20% (7/35) of HL patients were IDO-positive (IDO+), while the majority of cases in the group (80%, 28/35) were IDO-negative (IDO-). There were no significant differences in IDO expression between histological subtypes of HL. We also did not find any association between stage of disease and IDO expression in our study.
Patients with the absence of IDO expression tended to have a better response to the 1st line chemotherapy comparing to patients with positive IDO expression. The overall response rate was achieved in 71.4% (5/7) of IDO+ cases and in 92.9% (26/28) of IDO- cases.
The relapsed/refractory disease was more frequently found in HL cases with IDO+ compared IDO- expression (28.5% (2/7) versus 7.1% (2/28), respectively, p<0.05). We did not register any death of patients in IDO- group, while one patient in IDO+ group died during the follow-up period (median duration – 37 months; range 10–65 months).
ROC analysis revealed that the expression of IDO in the tumor is an important marker which is associated with clinical outcome of HL patients (Se=46.2 %; Sp=95 %; AUC=0.71, p=0.004).). The presence of IDO expression in pre-treated HL biopsies was associated with the reduced event-free survival (EFS) in HL patients. A 4-year EFS rate for IDO+ HL patients was 50% compared with 73% for IDO-negative HL patients (p=0.002). The prognostic significance of IDO+ expression in clinical outcome of HL (EFS) was also confirmed by multivariate analysis (HR=2.9; 95%CI 0.8-10.1, p=0.006)

Conclusion
On the base of the study, our findings suggest that IDO might be a promising marker for HL prognosis as well as represents an attractive target for HL immunotherapy in patients with poor outcome.

Session topic: 18. Non-Hodgkin & Hodgkin lymphoma - Biology

Keyword(s): Prognostic factor, Immunotherapy, Hodgkin's Lymphoma

Abstract: PB2069

Type: Publication Only

Background
Indoleamine 2,3-dioxygenase (IDO) is an inducible enzyme that catalyzes the initial and rate-limiting step in tryptophan along the kynurenine pathway. IDO is a key factor maintaining immune tolerance and expression and it correlates with poor clinical outcome in different types of cancer and hematological malignancies. It also plays a role in a lot of pathophysiological processes, such as antitumor and antimicrobial defense. IDO causes immunosuppression in the tumor microenvironment by tryptophan breakdown. Although, only several reviews have been made to evaluate IDO prognostic value and its expression value in hematological malignancies.

Aims
The aim of the study was to assess the impact of the IDO expression on clinical outcome in patients with Hodgkin’s lymphoma (HL).

Methods

A total number of 35 patients with HL were included in the group (10 males and 25 females; median age: 17-60 years, range: 38.5 years). Early stages (I-II) and advanced stages (III-IV) were diagnosed in 48.5% (17/35) and 51.4% (18/35) of patients, respectively. B-symptoms had 37.1% (13/35) of patients at the time of diagnosis. Patients were treated with ABVD or BEACOPP (14/esc) and radiation therapy. The mRNA expression level of IDO was measured in pre-treatment tumor tissue specimens from HL patients using real-time qPCR analysis.

Results

For 35 patients with HL, the overall response rate after the first-line therapy was 88.6 % (31/35). Progression of the disease during the therapy was observed in 11,4% of patients (4/35). Among the patients, who achieved a remission, 9 had relapses.
In our study, only 20% (7/35) of HL patients were IDO-positive (IDO+), while the majority of cases in the group (80%, 28/35) were IDO-negative (IDO-). There were no significant differences in IDO expression between histological subtypes of HL. We also did not find any association between stage of disease and IDO expression in our study.
Patients with the absence of IDO expression tended to have a better response to the 1st line chemotherapy comparing to patients with positive IDO expression. The overall response rate was achieved in 71.4% (5/7) of IDO+ cases and in 92.9% (26/28) of IDO- cases.
The relapsed/refractory disease was more frequently found in HL cases with IDO+ compared IDO- expression (28.5% (2/7) versus 7.1% (2/28), respectively, p<0.05). We did not register any death of patients in IDO- group, while one patient in IDO+ group died during the follow-up period (median duration – 37 months; range 10–65 months).
ROC analysis revealed that the expression of IDO in the tumor is an important marker which is associated with clinical outcome of HL patients (Se=46.2 %; Sp=95 %; AUC=0.71, p=0.004).). The presence of IDO expression in pre-treated HL biopsies was associated with the reduced event-free survival (EFS) in HL patients. A 4-year EFS rate for IDO+ HL patients was 50% compared with 73% for IDO-negative HL patients (p=0.002). The prognostic significance of IDO+ expression in clinical outcome of HL (EFS) was also confirmed by multivariate analysis (HR=2.9; 95%CI 0.8-10.1, p=0.006)

Conclusion
On the base of the study, our findings suggest that IDO might be a promising marker for HL prognosis as well as represents an attractive target for HL immunotherapy in patients with poor outcome.

Session topic: 18. Non-Hodgkin & Hodgkin lymphoma - Biology

Keyword(s): Prognostic factor, Immunotherapy, Hodgkin's Lymphoma

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