Recurrent or refractory primary central nervous lymphoma: therapeutic considerations

Abstract

Primary central nervous system lymphoma (PCNSL) is an uncommon variant of extranodal non-Hodgkin lymphoma (NHL) that involves the brain, leptomeninges, eyes or spinal cord without evidence of systemic disease. Despite the high complete remission rate achieved with aggressive first-line therapy, 10–35% of PCNSL are treatment refractory and 35–60% of patients relapse. Standard therapy for recurrent or refractory disease has not yet been established, although retrospective data suggests improvement in survival with salvage therapy. The reported survival after relapse of PCNSL varies between 2 months and 24 months, with most series reporting an average of 4–12 months. The outcomes depend on whether treatment is instituted or not, suggesting a need for treatment guidelines for these patients. We review therapeutic approaches and their outcomes in recurrent or refractory PCNSL.

Keywords::

• non-Hodgkin lymphoma
• primary CNS lymphoma
• salvage therapy
• stem cell transplantation

Financial & competing interests disclosure

M Ahluwalia has served on advisory board for Genentech/Roche. M Ahluwalia has served on speaker’s bureau for Merck. G Stevens has served on speaker’s bureau for UCB. The authors have no other 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.

No writing assistance was utilized in the production of this manuscript.

Key issues

• • Despite the high complete remission rate achieved with aggressive first-line therapy, 10–35% of primary central nervous system lymphoma (PCNSL) patients are treatment refractory and 35–60% of patients will relapse.

• • There are no standard guidelines or universally accepted algorithm for therapy for recurrent or refractory disease.

• • Salvage strategy should be recommended on the basis of previous treatments, response duration, site and extent of disease, prognostic factors and patient’s performance status.

• • Rechallenge with high-dose methotrexate (HD-MTX) is an option in PCNSL patients who relapse after prolonged initial response to MTX (>1 year).

• • The use of temozolomide with or without rituximab in relapsed PCNSL after an initial chemoradiotherapy regimen is recommended in elderly patients, who tend to have poor performance status.

• • Radiotherapy should be considered for previously un-irradiated patients.

• • High dose chemotherapy followed by stem cell rescue can be considered in patients with young age or good performance status.

• • The inclusion of patients with relapsed or refractory PCNSL should be strongly encouraged in prospective trials.