Second-Line Therapy for CNS Lymphoma: How Do Experts Choose?

By Greg Nowakowski, MD, Christian Grommes, MD, Avyakta Kallam, MD, Katherine Peters, MD, PhD, Andrew Moreno - Last Updated: December 2, 2024

Grzegorz Nowakowski, MD, of the Mayo Clinic, moderated a discussion on central nervous system (CNS) lymphoma with an expert panel featuring Christian Grommes, MD, of the Memorial Sloan Kettering Cancer Center; Katherine Peters, MD, PhD, of the Preston Robert Tisch Brain Tumor Center; and Avyakta Kallam, MD, of the City of Hope Comprehensive Cancer Center.

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In this segment of the panel discussion, the experts described their approaches in second-line management of CNS lymphoma. Dr. Peters emphasized the importance in such cases where patients have refractory disease that the disease be restaged, as this will influence treatment decision-making.

With methotrexate-based regimens as typical first-line therapy, depending on how soon relapse occur following the initial regimen, rechallenge with methotrexate might be considered. Other options the experts consider are lenalidomide and Bruton’s tyrosine kinase (BTK) inhibitors. They also stressed the importance of clinical trials, and Dr. Kallam remarked “I think whenever there’s a clinical trial option, that would take precedence over any of these approaches.”

On the question of whether to use lenalidomide as monotherapy or in combination, Dr. Kallam usually applies it as a single agent due to toxicity but may sometimes combine with rituximab. Regarding rituximab, Dr. Peters feels rituximab’s utility is mainly in polytherapy with methotrexate, and Dr. Nowakowski noted current uncertainty around this agent’s ability to penetrate the blood-brain barrier.

Regarding BTK inhibitors, the panel described them as being routinely used and well tolerated overall. Dr. Grommes spoke of how, based on clinical research, these agents should not be used if certain mutations are present. He usually uses ibrutinib in CNS lymphoma, but acknowledged with Dr. Nowakowski that more research is needed into the optimal dosing in this setting.

“We know that the higher the dose, the more you get in. I would prefer to use 840 [mg] but because of the doses available, usually I have to just go with the 560 [mg] dose level,” Dr. Grommes explained.

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