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CD163 is a predictive biomarker for prognosis of classical Hodgkin's lymphoma in Saudi patients.

ABSTRACT: Hodgkin's lymphoma (HL) is a hematological malignancy characterized by a minority of neoplastic cells outnumbered by tumor-associated macrophages (TAMs). The overexpression of the CD163 antigen by TAMs is considered to be a significant predictive biomarker for risk stratification. This is likely caused by a genetic single-nucleotide polymorphism (SNP) at the gene promoter. The aim of the present retrospective case-control study was to establish a gene expression profile of a specific biomarker for classical HL (CHL) in order to predict the outcome and survival of CHL patients in Saudi Arabia. The protein expression of CD163 on TAMs was studied using immunohistochemistry (IHC). A prognosis index was calculated for the CD163 protein to assess the risk stratification of CHL. Genotyping of selected SNPs of this antigen was performed for 100 CHL cases and controls. The analysis revealed that the CD163 protein expression level was significantly correlated with disease relapse (DR) and overall survival (OS). In addition, the CD163 index threshold (15.0) was found to be significantly correlated with the relapse rate. Among the studied CD163 SNPs, rs75608120 exhibited a significant correlation with the DR rate of CHL patients, but not with OS. The findings of the present study confirmed that CD163 is a specific marker for TAMs, and its overexpression by TAMs is significantly associated with relapse and reduced survival post-therapy. In addition, a new methodology of indexing CD163 protein expression for HL risk stratification was proposed. Thus, the present study identified a specific predictive molecular and antigenic biomarker for CHL prognosis.

SUBMITTER: Ahmed HAS

PROVIDER: S-EPMC6535641 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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CD163 is a predictive biomarker for prognosis of classical Hodgkin's lymphoma in Saudi patients.

Ahmed Huda Al Sayed HAS Raslan Wasim Fawzi WF Deifalla Abdel Halim Salem AHS Fathallah Mohammad Dahmani MD

Molecular and clinical oncology 20190424 1

Hodgkin's lymphoma (HL) is a hematological malignancy characterized by a minority of neoplastic cells outnumbered by tumor-associated macrophages (TAMs). The overexpression of the CD163 antigen by TAMs is considered to be a significant predictive biomarker for risk stratification. This is likely caused by a genetic single-nucleotide polymorphism (SNP) at the gene promoter. The aim of the present retrospective case-control study was to establish a gene expression profile of a specific biomarker f ...[more]

PMID: 31289681

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Project description:BackgroundRelapsed or refractory classical Hodgkin lymphoma (cHL) remains a difficult treatment challenge. Although checkpoint inhibitors (CPI) have provided clinical benefit for these patients, responses are generally not durable, and progression eventually occurs. Discovering combination therapies which maximize the immune response of CPI therapy may overcome this limitation. We hypothesized that adding ibrutinib to nivolumab will lead to deeper and more durable responses in cHL by promoting a more favorable immune microenvironment leading to enhanced T-cell-mediated anti-lymphoma responses.MethodsWe conducted a single arm, phase II clinical trial testing the efficacy of nivolumab in combination with ibrutinib in patients ≥18 years of age with histologically confirmed cHL who had received at least one prior line of therapy. Prior treatment with CPIs was allowed. Ibrutinib was administered at 560 mg daily until progression in combination with nivolumab 3 mg/kg IV every 3 weeks for up to 16 cycles. The primary objective was complete response rate (CRR) assessed per Lugano criteria. Secondary objectives included overall response rate (ORR), safety, progression free survival (PFS), and duration of response (DoR).ResultsA total of 17 patients from two academic centers were enrolled. The median age of all patients was 40 (range 20-84). The median number of prior lines of treatment was five (range 1-8), including 10 patients (58.8%) who had progressed on prior nivolumab therapy. Most treatment related events were mild (<Grade 3) and expected from the individual side effect profiles of ibrutinib and nivolumab. In the intent to treat population (n = 17), the ORR and CRR were 51.9% (9/17) and 29.4% (5/17), which did not meet the prespecified efficacy endpoint of a CRR of 50%. In patients who received prior nivolumab therapy (n = 10), the ORR and CRR were 50.0% (5/10) and 20.0% (2/10), respectively. At a median follow up of 8.9 months, the median PFS was 17.3 months, and the median DOR was 20.2 months. There was no statistically significant difference in median PFS between patients who received previous nivolumab therapy versus patients who were nivolumab naïve (13.2 months vs. 22.0 months, p = 0.164).ConclusionsCombined nivolumab and ibrutinib led to a CRR of 29.4% in R/R cHL. Although this study did not meet its primary efficacy endpoint of a CRR of 50%, likely due to enrollment of heavily pretreated patients including over half of who had progressed on prior nivolumab treatment, responses that were achieved with combination ibrutinib and nivolumab therapy tended to be durable even in the case of prior progression on nivolumab therapy. Larger studies investigating the efficacy of dual BTK inhibitor/immune checkpoint blockade, particularly in patients who had previously progressed on checkpoint blockade therapy, are warranted.

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CD163 is a predictive biomarker for prognosis of classical Hodgkin's lymphoma in Saudi patients.

Publications

CD163 is a predictive biomarker for prognosis of classical Hodgkin's lymphoma in Saudi patients.

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