BTK inhibitors and novel agents are reshaping first-line treatment for primary brain lymphoma.

BTK inhibitors and novel agents are reshaping first-line treatment for primary brain lymphoma.

Primary central nervous system lymphoma (PCNSL) is treated primarily with high-dose methotrexate (HD-MTX), but new agents presented at ASH 2025 are changing this paradigm. This editorial review summarizes key highlights: BTK inhibitors, immunomodulators, selinexor (an XPO1 inhibitor), and anti-PD-1 antibodies are being combined with HD-MTX in first-line treatment.

Emerging combinations are improving response rates and survival while potentially enabling less toxic maintenance approaches. The integration of these novel agents represents a significant shift toward more effective, targeted PCNSL management.

This is an evolving space with multiple ongoing trials.

Key Findings

• HD-MTX remains the cornerstone of PCNSL treatment but new combinations are improving outcomes
• BTK inhibitors, immunomodulators, selinexor, and anti-PD-1 antibodies are entering first-line combinations
• Emerging combinations improving response rates and survival vs. HD-MTX alone
• Multiple trials reported at ASH 2025 demonstrate efficacy signals
• Treatment landscape is rapidly evolving toward targeted combination approaches

Implications

Oncologists treating PCNSL should be aware of evolving data supporting novel agent combinations with HD-MTX. Clinical trial enrollment should be prioritized. The potential for more durable remissions with combination approaches has real patient impact.

Caveats

Editorial review of meeting abstracts; abstract-only. Phase and design of referenced trials not fully specified. Data from ASH 2025 presentations—not yet peer-reviewed publications. Rapidly changing field.

Source: Journal of hematology & oncology — 2026-04-09