Brain with glowing neural pathways and a feather, symbolizing targeted therapy in lymphoma.

Ibrutinib's New Role: How This Targeted Therapy Offers Hope in PCNSL

Theo Raines in Health & Wellness December 2025 • 4 min read.

"Discover how ibrutinib, a well-known cancer drug, is showing promise in treating primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL), offering new hope and targeted solutions for these challenging conditions."

Ibrutinib, a groundbreaking oral medication, has revolutionized the treatment of several blood cancers. Initially approved for mantle cell lymphoma, its use has expanded to chronic lymphocytic leukemia, Waldenström's macroglobulinemia, and marginal zone lymphoma. Now, research suggests it could also be a game-changer for primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL).

A recent study by Grommes and colleagues sheds light on ibrutinib's effectiveness in treating these specific types of lymphoma. This research highlights ibrutinib's ability to target and inhibit Bruton tyrosine kinase (BTK), a crucial protein in B-cell function. By doing so, ibrutinib promotes significant and lasting responses in patients with PCNSL and SCNSL.

This article delves into the details of this study, exploring how ibrutinib works, the encouraging results observed, and the potential implications for future treatment strategies. We'll break down the science in an accessible way, revealing why this development offers new hope for those affected by these challenging conditions.

Ibrutinib's Impact on PCNSL and SCNSL: What the Study Revealed

Brain with glowing neural pathways and a feather, symbolizing targeted therapy in lymphoma.

The study conducted by Grommes and colleagues was an open-label, single-center trial designed to determine the maximum tolerated dose of ibrutinib in patients with relapsed or refractory PCNSL/SCNSL. The trial expanded to assess both the safety and effectiveness of ibrutinib at doses of 560 mg and 840 mg daily.

The results were promising:

PCNSL: Among 13 patients with PCNSL, 5 achieved a complete response (CR), and 5 experienced a partial response (PR). The median progression-free survival (PFS) was 4.6 months, and the median overall survival (OS) was 15 months.
SCNSL: Out of 7 patients with SCNSL, 4 achieved CR, and 1 had a PR. The median PFS was 7.43 months, and the median OS had not been reached.

These response rates are notably higher than typically seen in DLBCL arising outside the CNS, suggesting that PCNSL and SCNSL may have unique biological characteristics that make them more susceptible to ibrutinib's effects. The research team further investigated these differences through genomic sequencing.

The Future of Ibrutinib in CNS Lymphoma Treatment

This study, along with other recent findings, underscores the potential of ibrutinib as a valuable treatment option for PCNSL and SCNSL. While these results are encouraging, researchers are also exploring ways to overcome resistance to ibrutinib. The study identified that mutations in the CD79B protein, associated with activation of the mTOR pathway, can lead to diminished response to ibrutinib. However, preclinical research suggests that combining ibrutinib with PI3K inhibitors could overcome this resistance mechanism.

Furthermore, the potential for combining ibrutinib with other therapies, such as checkpoint inhibitors, is being explored. Preclinical models suggest that this combination could enhance antitumor immunity, offering a synergistic approach to treatment.

As research continues, ibrutinib holds great promise for improving outcomes for patients with PCNSL and SCNSL. Future studies will focus on refining treatment strategies, identifying biomarkers for predicting response, and exploring combination therapies to maximize efficacy and minimize resistance. This research paves the way for a brighter future in the treatment of these challenging lymphomas.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1158/2159-8290.cd-17-0714, Alternate LINK

Title: Spotlight On Ibrutinib In Pcnsl: Adding Another Feather To Its Cap

Subject: Oncology

Journal: Cancer Discovery

Publisher: American Association for Cancer Research (AACR)

Authors: Aparna Lakshmanan, John C. Byrd

Published: 2017-08-31

Everything You Need To Know

What is ibrutinib, and what conditions is it now being used to treat?

Ibrutinib is an oral medication initially used for blood cancers like mantle cell lymphoma, chronic lymphocytic leukemia, Waldenström's macroglobulinemia, and marginal zone lymphoma. Recent research indicates it can also be effective against primary central nervous system lymphoma (PCNSL) and secondary central nervous system lymphoma (SCNSL) by targeting Bruton tyrosine kinase (BTK).

What were the main findings of the Grommes and colleagues study regarding ibrutinib's effectiveness in treating PCNSL and SCNSL?

In a study by Grommes and colleagues, ibrutinib showed promising results in treating PCNSL and SCNSL. For PCNSL, 5 out of 13 patients achieved a complete response (CR), and 5 had a partial response (PR), with a median progression-free survival (PFS) of 4.6 months and a median overall survival (OS) of 15 months. In SCNSL, 4 out of 7 patients achieved CR, and 1 had a PR, with a median PFS of 7.43 months, and the median OS was not reached.

How does ibrutinib work to combat PCNSL and SCNSL?

Ibrutinib works by targeting and inhibiting Bruton tyrosine kinase (BTK), a protein crucial for the function of B-cells. By inhibiting BTK, ibrutinib disrupts the signaling pathways that allow lymphoma cells to survive and proliferate, promoting significant and lasting responses in patients with PCNSL and SCNSL.

What causes resistance to ibrutinib, and how can this resistance be overcome?

Mutations in the CD79B protein, which are associated with the activation of the mTOR pathway, can lead to resistance to ibrutinib. However, preclinical research suggests that combining ibrutinib with PI3K inhibitors could potentially overcome this resistance mechanism, offering a way to improve treatment outcomes for patients who develop resistance.

Besides the effects of ibrutinib, what other significant insights does this research provide for understanding and treating PCNSL and SCNSL?

While the study focuses on the effects of ibrutinib, it also highlights the importance of genomic sequencing in understanding the unique biological characteristics of PCNSL and SCNSL. These characteristics may make these lymphomas more susceptible to ibrutinib's effects compared to DLBCL arising outside the CNS. Further research into these genomic differences could lead to the development of even more targeted and effective treatments. Furthermore, the study's methodology as an open-label, single-center trial helps define parameters for future broader studies that could include randomized controlled trials.