Primary CNS Lymphoma

Half of primary CNS lymphoma occurs in the 60 and older age group..

Lymphoma can arise at many different sites in the body, and some sites are more rare than others. For rare cancers, sometimes there is no such thing as a standard therapy. In these cases, doctors do their best to find a treatment that will have the greatest efficacy with the least toxicity. Your age and general state of health can be big factors in deciding which therapies might be right for you.

Primary Central Nervous System Lymphoma

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive type of non-Hodgkin lymphoma.

The prognosis tends to be especially poor for those in the 60 and older age group.

Half of all cases of PCNSL occur in this age group.

Although it’s rare, PCNSL has been on the rise over the last 30 years. A study of 579 older patients diagnosed with PCNSL in the 1990s in the U.S. showed the median survival was only 7 months. At that time, whole brain radiotherapy alone was the most common treatment in this age group, at 46 percent.

Although older individuals may tolerate aggressive systemic chemotherapy for PCNSL, they tend to have a worse prognosis compared to younger patients. Older people are more seriously affected by toxicity, especially the neurological side effects following whole brain radiotherapy.

Patients with primary CNS lymphoma are generally treated in two phases: the induction phase, meant to induce remission, and the consolidation phase, given once remission is achieved.

The most common treatment has been high-dose Trexall (methotrexate)-based chemotherapy followed by consolidative whole-brain radiotherapy, but many patients relapse and die from lymphoma or have an increased risk of toxicity to the nervous system.

Treatment Patterns

Given this challenge, Dr. Benjamin Kasenda and colleagues went looking systematically for studies on therapies being used for this disease in the over-60 population. Specifically, they wanted to know which therapies oncologists used as first-line therapy most often in patients with newly diagnosed PCNSL.

They found 20 published studies, including information from 783 patients who met their study criteria -- that is, newly diagnosed with PCNSL, age over 60 years and an intact/healthy immune system. Overall, they found the first-line treatments for individuals in this group varied, and that there was no definite standard treatment for older patients with PCNSL.

Key Findings

  • Researches also found that, over the last decade, prognosis in this age group has improved.
  • Therapies that involved high-dose methotrexate were associated with significantly better results.
  • High-dose methotrexate plus at least two other IV drugs -- aggressive treatment -- compared to high-dose methotrexate plus oral chemotherapy were NOT associated with improved response or survival.
  • In people who received high-dose-methotrexate based chemotherapy, whole brain radiotherapy was associated with improved survival, but also with an increased risk of neurological side effects.
  • Methotrexate is now the most widely studied drug in the treatment of PCNSL. Fewer patients are now being treated with whole brain radiation therapy, only.

    Bottom Line

    This study looked back at what had been done in the past -- it was a retrospective and observational study--and therefore it has some important limitations. However, more definitive data from PCNSL prospective trials in elderly people are not available. Here's what this group concluded:

    • High-dose-methotrexate-based therapy should be offered even to frail patients, whenever possible.
    • First-line treatment with combinations of high-dose methotrexate along with oral agents -- procarbazine or temozolomide, for example—also seemed promising and deserved to be further investigated.
    • Whole brain radiotherapy may improve outcome, but it’s associated with increased risk for neurological side effects.

    Finally, Kasenda and colleagues highlighted the need for prospective trials designed for elderly PCNSL patients.


    Kasenda B, Ferreri AJM, Marturano E, et al. First-line treatment and outcome of elderly patients with primary central nervous system lymphoma (PCNSL) - a systematic review and individual patient data meta-analysis. Ann Oncol. 2015. [Epub ahead of print].

    Roth P, Hoang-Xuan K. Challenges in the treatment of elderly patients with primary central nervous system lymphoma. Curr Opin Neurol. 2014; 27: 697-701.

    Panageas KS, Elkin EB, Ben-Porat L, et al. Patterns of treatment in older adults with primary central nervous system lymphoma. Cancer 2007; 110: 1338-1344.

    Ferreri AJM, Cwynarski K, Pulczynski E, et al. Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial. Lancet Haematology. 2016;5; e217-e227.


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