Advances in therapeutic strategies for primary CNS B-cell lymphomas

ABSTRACT

Introduction

Primary CNS lymphoma (PCNSL) has traditionally been treated with induction HD-MTX-based chemotherapy, followed by consolidation whole-brain radiotherapy. However, this approach is associated with significant neurocognitive complications, especially in older patients. Therefore, different consolidation protocols have been evaluated. High-dose chemotherapy followed by autologous stem cell transplantation (HD-ASCT) has the best long-term survival outcomes in younger patients.

Areas covered

In this review of the literature, we focus on the overall therapeutic strategy and advances in the management of the aggressive primary CNS B-cell lymphomas.

Expert opinion

In young and fit PCNSL patients, HD-ASCT is the preferred consolidation strategy to achieve long-term survivals. Older patients with good performance status should also be evaluated for MTX-based induction polychemotherapy followed by ASCT. However, management of PCNSL patients remains challenging, and new avenues with targeted therapies are under investigation. To date, ibrutinib, lenalidomide, and immune checkpoint inhibitors appearto be promising in PCNSL. However, as monotherapy, durable responses are less likely to be achieved. Unfortunately, when combined with chemoimmunotherapy, considerable toxicity and mortality have been reported. Clinical trials on these molecules are aiming to reduce toxicity and maintain responses. CAR-T-cell therapy has recently emerged as a further option. It has shown efficacy in patients with secondary CNS lymphoma, with few but encouraging results in primary CNSL.

KEYWORDS:

• CNS
• LYMPHOMA
• PCNSL
• autologous transplant in PCNSL
• IBRUTINIB
• LENALIDOMIDE
• checkpoint inhibition anti PD-1
• mTOR inhibitors
• CAR-T

Article highlights

• CNS lymphoma remains a great unmet medical need.

• In young and fit PCNSL patients, MTX-based polychemotherapy induction followed by HD-ASCT remains the preferred standard of care to achieve long-term survivals.

• Older patients with good performance status and no comorbidity should be considered for MTX-based polychemotherapy followed by ASCT.

• Patients who are not candidates for intensive therapy may benefit from temozolomide alone or plus rituximab.

• WBRT is associated with a substantial risk of cognitive impairment especially in older patients and its use remains debatable.

• Several novel agents in PCNSL such as ibrutinib, lenalidomide, and immune checkpoint inhibitors showed promising results, but further studies are needed to optimize combination protocols with the aim of reducing toxicity and maintaining responses.

• CAR-T-cell therapy has shown efficacy in patients with secondary SCNSL with limited, but quite encouraging, results in PCNSL.

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 study is partially supported by grant from Piaggio S.p.A. and by a grant for academic and research collaboration from the Armed Forces College of Medicine, Cairo, Egypt to C.T.