Wednesday, 4 October 2017

#NeuroSpeak & #ClinicSpeak: natalizumab and lymphomas

PML is not the only complication associated with natalizumab therapy. #NeuroSpeak #ClinicSpeak

Summary: Albeit rare, natalizumab is increasingly being associated with CNS lymphoma. This is probably due to reduced immune surveillance as a result of natalizumab blocking lymphocyte trafficking into the CNS. 

Evolution designed the immune system to fight infections and to clear pre-malignant cells from the body before they cause a problem. To do this the immune system has developed surveillance systems that depends on trafficking of cells from the blood into the tissues. If you block trafficking of cells into the CNS (central nervous system) with drugs, such as natalizumab, then you increase the chances of developing malignancies in the target organ. It is therefore no surprise that we are beginning to see an increasing number of case reports of primary CNS lymphomas in pwMS on long-term natalizumab. This potential complication was predicted more than a decade ago by several insightful people in the field. Please be aware that to the best of my knowledge this complication is rare, but acts as a reminder to pwMS on natalizumab that you need to be vigilant of new symptoms that could herald CNS complications. PML is definitely not the only severe complication associated with natalizumab therapy. 


Na et al. Central nervous system lymphoma associated with natalizumab.
J Clin Neurosci. 2014 Jun;21(6):1068-70.

Patients with primary central nervous system lymphoma (PCNSL) after treatment with natalizumab have been considered co-incidental. We report another case of PCNSL in a patient where the explosive onset suggests a causal link.

Nixon et al. Natalizumab Associated Primary Central Nervous System Lymphoma. World Neurosurg. 2017 Sep 26. pii: S1878-8750(17)31647-9.

Natalizumab, a selective adhesion molecule inhibitor binding to α-4 subunit of integrin, has emerged to be an effective immuno-modulator especially in the treatment of relapsing-remitting Multiple Sclerosis and Crohn's disease. Literature documenting the development of progressive multifocal leukoencephalopathy from its use is widely available. However, only handful of reports cites the development of a more concerning pathology, primary CNS lymphoma (PCNSL) from its administration, thereby triggering a debate on a possible causal association. Considering paucity of literature and the prognostic severity of PCNSL, we herein report its development in a young woman with Crohn's disease that was previously administered Natalizumab. Additionally, we provide a comprehensive review of literature on cases of lymphoma development following Natalizumab use to re-emphasize the drug association with PCNSL, if at all.

CoI: multiple

5 comments:

  1. How does CNS Lymphomas defer from Hodgkin?

    This matter is on top of my mind as I am showing Hodgkin symptoms....

    Can you please develop more this post to highlight which symptoms long term Tysabri users should be aware of?

    Tony Fonda

    ReplyDelete
    Replies
    1. Hodgkin's lymphoma (HL) is a peripheral lymphoma and very rarely involves the CNS. About 50-60% of HL's are caused by EBV. In comparison, CNS lymphomas arise in the CNS and almost all B-cell lymphomas. Saying that there are a small number of T-cell lymphomas that involve the CNS; these tend to be angoicentric or grow around blood vessels. In the presence of immunosuppression EBV is commonly the driver of the CNS B-cell lymphomas.

      Please note that Hodgkin's lymphoma is not one disease and is generally split into several types. The prognosis also varies depending on subtype.

      Interestingly, family members of pwMS are at increased risk of developing lymphoma. Could this be due to EBV?

      Delete
    2. Thanks for that - would you advise UK MSers to discuss such matters with their GPs or directly with their neurologists?

      Tony

      Delete
  2. Would it be the same for Fingolimod users as it works much the same as Tysabri?

    ReplyDelete
  3. How rate is it? Rarer than PML?

    Who do you think that are on higher risk of developing lymphomas?

    ReplyDelete

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