Challenges in the treatment of elderly patients with primary central nervous system lymphoma

Approximately 50% of all patients with primary central nervous system lymphoma (PCNSL) are 60 years or older and may therefore be considered as elderly. Although the diagnostic work-up is basically the same in young and in elderly patients, therapeutic strategies vary considerably. Here, we review the characteristics of elderly PCNSL patients with a particular focus on advances in the optimization of treatment regimens.

Age has been repeatedly confirmed as a major therapy-independent negative prognostic factor. Benefit from treatment and the tolerability of tumor-specific therapy, particularly whole-brain radiotherapy, are significantly lower in the elderly patients. Still, for patients with newly diagnosed PCNSL, several studies emphasized the indisputable role of high-dose methotrexate as backbone for any therapy regimen also in elderly patients. However, the durability of responses to primary chemotherapy is significantly shorter than in young patients. Recent data from a randomized phase II study for elderly PCNSL patients suggest that the combination of high-dose methotrexate, procarbazine, vincristine and cytarabine is superior to methotrexate in combination with temozolomide.

Current efforts aim at treating elderly PCNSL patients within clinical trials that are specifically designed for this group of patients. Determining adapted consolidation and/or maintenance treatment to improve disease control in responding patients are the main challenges to be faced by future trials. Together with a better understanding of age-specific changes in the biology of PCNSL, this will pave the road for elderly tailored therapies.