Implications of recent molecular achievements in early diagnosis and precision treatments for primary CNS lymphoma

ABSTRACT

Introduction: Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) represents a relevant challenge in onco-hematology. PCNSL has specific molecular profile and biological characteristics that distinguish it from systemic DLBCL. Several translational studies have allowed for significant improvement in the knowledge about its genomic and molecular profile. High-dose-methotrexate-based chemotherapy followed whole-brain irradiation or autologous stem cell transplantation is the most commonly used therapeutic approach in PCNSL patients.

Areas covered: This work provides an overview of the new biomarkers of PCNSL, focusing on their potential diagnostic, predictive and prognostic role. Publications in English language, peer-reviewed, high-quality international journals, were identified on PubMed.

Expert opinion: Early diagnosis, a better antitumor response definition and recognition of new effective treatments are important research fields aiming to improve PCNSL outcome and management. The acquisition of new molecular and genomic knowledge in PCNSL has allowed for the attainment of promising diagnostic and prognostic tools as well as the development of clinical trials with new therapeutic approaches beyond chemotherapy agents, which have demonstrated activity in refractory/relapsed PCNSL and deserve to be investigated in first-line therapy.

KEYWORDS:

• Primary CNS lymphoma
• CSF biomarkers
• checkpoint inhibitors
• immunomodulatory drugs
• mTOR inhibitors
• myd88
• interleukins
• btk inhibitors

Article highlights

• Primary Diffuse Large B-Cell Lymphoma of the central nervous system (CNS) is a rare extra nodal lymphoma. Despite recent advances, diagnosis and treatment remain important challenges for the clinicians.

• Molecular markers and genetic alterations detected on cerebrospinal fluid (CSF) are emerging tools for early diagnosis and disease monitoring. Prospective and large studies investigating and validating easily reproducible tests with more precise cut off of biomarkers need to be designed before their use in clinical practice.

• The identification of new radiological and biological prognostic and predictive factors need to be developed in PCNSL patients with the aim to move toward a personalized therapeutic approach, including targeted therapy (such as Bruton Tyrosine Kinase inhibitors and immunomodulators), checkpoint inhibitors and/or engineering immune cell therapy, both in first line and in salvage setting.

• Less toxic and more manageable drugs than chemotherapy agents need to be evaluated in the first line setting as induction, and in elderly and frail patients as consolidation/maintenance.

• Targeted and immunomodulatory therapy showed fast and high response rate, but of short-lasting. Combination of new agents and chemotherapy is object of investigation in ongoing study both in refractory/relapsed setting and in first line.

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Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

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

Additional information

Funding

This manuscript was not funded.