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ICML 2025 | The future of primary CNS lymphoma treatment: BTK-targeting agents and immunotherapy
Lakshmi Nayak, MD, Dana-Farber Cancer Institute, Boston, MA, comments on the future of primary central nervous system (CNS) lymphoma treatment. Dr Nayak highlights the potential of BTK-targeting agents and CAR T-cell therapy, as well as bispecific T-cell engagers. This interview took place during the 18th International Conference on Malignant Lymphoma (18-ICML) in Lugano, Switzerland.
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Transcript
You know, the field of primary CNS lymphoma has recently become more exciting since evaluation of the genomics of primary CNS lymphoma, but also understanding the microenvironment, specifically the microenvironment of the brain and the spinal fluid, and increasing work, preclinical work in this regard, has led to several discoveries and promising new therapies. So targeting BTK and the next generations of BTK inhibitors, developing further therapies to counteract the mechanisms of resistance to BTK inhibitors, it would be the next way to go, are also combining BTK inhibitors with even chemotherapy in the upfront setting and bringing such agents into the upfront setting seems like the next best option to move forward...
You know, the field of primary CNS lymphoma has recently become more exciting since evaluation of the genomics of primary CNS lymphoma, but also understanding the microenvironment, specifically the microenvironment of the brain and the spinal fluid, and increasing work, preclinical work in this regard, has led to several discoveries and promising new therapies. So targeting BTK and the next generations of BTK inhibitors, developing further therapies to counteract the mechanisms of resistance to BTK inhibitors, it would be the next way to go, are also combining BTK inhibitors with even chemotherapy in the upfront setting and bringing such agents into the upfront setting seems like the next best option to move forward. And then from the standpoint of immunotherapy and cellular therapy, we have previously shown that CAR T-cell expansion in the nervous system is achievable and also have shown evidence of efficacy. In fact, at this conference, too, there is an abstract presentation by Dr Johnson presenting the role of next-generation CAR T-cell therapy, which we participated in as well. So CAR T-cell therapy and novel agents seem to be the future for primary CNS lymphoma and also, you know, further studies looking at bispecific T-cell engagers, et cetera, also seems to be the way to go. And trying to first have proof of concept studies to investigate them, to understand the efficacy, and then move them into the upfront setting so that hopefully we can try to cure the majority of the patients in the upfront setting rather than wait for their relapses to occur, which can be quite harsh on especially brain tumor patients because every time there is a recurrence, that is an extra insult on the brain. And extra insult leads to damaging effects, and sometimes with more and more insults can be irreversible. So trying to get these therapies in the upfront setting to prevent further insults to the brain would be, from the tumor itself, would be ideal.
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