A peek behind the paper – Katy Peters on ibrutinib in primary central nervous system diffuse large B-cell lymphoma

Written by Katy Peters (Duke University Medical Center)

Take a look behind the scenes of a recent Review article published in the journal CNS Oncology entitled, ‘Ibrutinib in primary central nervous system diffuse B-cell lymphoma‘, as we ask corresponding author Katy Peters (Duke University Medical Center, NC, USA) about treatment options for primary central nervous system lymphoma (PCNSL), including the challenges yet to be overcome before ibrutinib could be approved for use in regular clinical practice. 

What inspired you to write this review?

PCNSL is a rare form of diffuse B-cell lymphoma that involves the brain, spinal cord, or leptomeninges, without evidence of systemic lymphoma and is responsible for only 3% of all primary CNS tumors. Given the rarity of this cancer, clinical trials and treatment recommendations for PCNSL are limited. Thus, we were inspired to write this review to explore treatment options for PCNSL, particularly in the recurrent setting.

Could you provide us with an overview of what is discussed in your article?

We discuss the use of a new promising targeted therapeutic agent for recurrent or relapsed PCNSL called ibrutinib. The target for ibrutinib is BTK, a non-receptor protein kinase that is critical for amplification of B-cell signaling and now a target to combat B-cell lymphomas. We reviewed the use of ibrutinib in systemic lymphomas and how clinicians are currently studying the role of ibrutinib for PCNSL.

What are the current treatment options for patients with PCNSL?

The standard of care for newly diagnosed PCNSL is polychemical high-dose intravenous methotrexate containing regimens. Clinicians have utilized whole-brain radiation therapy, but resultant CNS toxicity has prompted investigators to explore regimens with lower total doses of radiation therapy or avoidance of radiation therapy entirely. As for recurrent primary central nervous lymphoma, there is no standard of care regimen available and much is needed to move this area of research forward for patients with this illness.

What challenges are still to overcome before ibrutinib could be approved for use in regular clinical practice?

Understanding the true extent of toxicities that accompany treatment with ibrutinib will be critical for clinicians to put this agent into regular practice. Of course, a large randomized controlled trial would be the gold standard, but given the rarity of PCNSL, this remains challenging. With cooperation from national and international consortiums, trials to evaluate this rare disease can be undertaken.

What are the next steps for research into BTK inhibitors for the treatment of PCNSL?

The next step for the development of BTK inhibitors is to understand better which patients respond to BTK inhibitor therapy. As we touched on in the manuscript, CARD11 R179Q mutant tumors are unlikely to react to ibrutinib therapy. Therefore the rigorous design of future clinical trials with BTK inhibitors should include correlative genomic analysis of specimens.

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The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Neuro Central or Future Science Group.

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