Aggressive Non-Hodgkin lymphomas: risk factors and treatment of central nervous system recurrence

ABSTRACT

Introduction: Secondary central nervous system lymphoma (SCNSL) is a potentially fatal event in the setting of aggressive Non-Hodgkin Lymphomas. Nowadays, despite of the very poor outcome of SCNSL, several studies are going to identify the high-risk patients’ subgroup that could early develop this detrimental event and in whom the central nervous system (CNS) prophylaxis could improve survival.

Areas covered: Herein, the authors will review the prophylactic and treatment strategy for SCNSL, focusing on the identification of high-risk subgroup.

Expert opinion: The validated CNS International Prognostic Index score lacks sensitivity. The role of prophylaxis has been suggested as an important step for selected patients. Intrathecal prophylaxis is always less consolidated, due to its doubtful efficacy, whereas systemic high-dose methotrexate is becoming the favored option to reduce CNS relapse in high-risk aggressive lymphomas. However, there is no a clear guideline to help physicians in clinical practice. The encouraging results on treatment of primary CNS lymphoma prompted new therapeutic strategies for SCNSL, although larger and randomized prospective studies are needed. Future efforts should be addressed to better clarify these open questions.

KEYWORDS:

• CNS
• CNS-IPI
• lymphoma
• prophylaxis
• risk factors
• relapse
• treatment

Article highlights

• SCNSL is a rare and devastating complication in the setting of aggressive NHL, with a median survival of 2–5 months.

• Several clinical features are used to classify the high-risk patients. Nowadays, the most useful score to define this category of patients is CNS-IPI, which has been recently validated. Actually, the use of this clinical score is debated because of the low diagnostic sensitivity.

• Combination of clinical, pathological and molecular features, as information of COO subtype, MYC and BCL2 expression may improve the identification of high-risk patients and should be investigated in a large series of prospective cases.

• IT therapy was mostly used as CNS prophylaxis, but the cumulative data so far have challenged its efficacy and more evidence in reducing the incidence of CNS has been showed by systemic HD-MTX and/or HD-Ara-C approach.

• Treatment of secondary CNS recurrence in patients with aggressive lymphomas remains an important, unmet clinical need. A standard therapeutic approach has not been defined yet. Intensified chemo-immunotherapy regimens, including HD-MTX and drugs able to across the BBB with autologous stem cell transplantation, have been investigated and encouraging results have been produced.

• Novel drugs could hopefully have a key role in improving the current therapeutic approach.

This box summarizes key points contained in the article.

Declaration of interest

A Chiappella as acted on advisory boards for Celgene and Janssen and has received lecture fees from Amgen, Celgene, Janssen, Nanostring, and Roche. U Vitolo has acted on advisory boards for Roche, Janssen, and Celgene and has received lecture fees for Roche, Celgene, Janssen, Gilead and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.