An update on disease biomarkers for Hodgkin lymphoma

ABSTRACT

Introduction

Hodgkin Lymphoma (HL) carries an overall excellent prognosis for young patients treated with multimodal therapy. Predicting an individual patient’s prognosis is currently heavily dependent on imaging modalities such as Positron Emission Tomography (PET).

Areas covered

Potential biomarkers from serum, tissue, circulating nucleic acids and non-tumor derived cells have all been reported to be of prognostic relevance in HL. We review a range of these biomarkers and discuss the integration of new biomarkers into individualized patient care.

Expert opinion

Better prognostic markers are needed to predict an individuals response to HL therapy. Interim PET-scan improves the ability to predict long-term treatment responders. However, it is our opinion that supplementation of PET results with additional biomarkers (including circulating tumor DNA, protein biomarkers, tissue genotyping and metabolic tumor volume) are likely to improve risk stratification for future patients with HL.

KEYWORDS:

• Hodgkin lymphoma
• prognosis
• treatment
• chemotherapy
• TARC
• cell free DNA
• tumor microenvironment
• pet scan
• metabolic tumor volume
• genotyping

Article Highlights

• Early PET scan (after 2 cycles of chemotherapy) is currently the most sensitive predictor of long-term survival in HL.

• PET-adapted therapy is emerging as a means to limit therapy related toxicity in patients who demonstrate early response.

• There is a lack of disease specific biomarkers for monitoring patients after completion of first-line therapy or at relapse.

• TARC is the most widely validated protein biomarker detectable in serum for prognosis and treatment monitoring in HL.

• TARC combined with other biomarkers shows improved sensitivity and specificity.

• The cellular composition of the tumour microenvironment in HL impacts prognosis.

• Tumour associated macrophages are the most validated prognostic component of the tumour microenvironment.

• Molecular profiling of tumour biopsies is likely to lead to improved prognostication of clinical risk groups.

• Emerging application of cell free DNA (liquid biopsy) offers promise for prognostic monitoring during therapy, at the end of treatment and in minimal residual disease detection.

Declaraton of Interest

M Cirillo receives West Australian Cancer Oncology Group (2017) Fellowship Funding” and S Borchmann is supported by Else Kröner-Fresenius-Stiftung, Grant No. 2016‐Kolleg‐19, Deutsche Forschungsgemeinschaft (DFG), Grant No. EN 179/13-1 and Frauke Weiskam + Christel Ruranski-Stiftung, Grant No. T 0136 – 33.661.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was supported by Else Kröner-Fresenius-Stiftung, [Grant No. 2016‐Kolleg‐19], Deutsche Forschungsgemeinschaft (DFG), [Grant No. EN 179/13-1] and Frauke Weiskam + Christel Ruranski-Stiftung, [Grant No. T 0136 – 33.661].