Comparative Analysis of BTK Inhibitors Versus Lenalidomide for First-Line Maintenance in PCNSL

Overview

This multicenter retrospective study evaluated the efficacy and safety of BTK inhibitors (BTKis) versus lenalidomide as first-line maintenance therapies in newly diagnosed primary central nervous system lymphoma (PCNSL) patients achieving remission after induction. Both agents demonstrated potential to prolong remission with manageable toxicity profiles, offering alternative maintenance strategies for patients ineligible for autologous stem cell transplantation (ASCT).

Background

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma with limited treatment options. High-dose methotrexate (HD-MTX)-based induction therapy followed by consolidation with ASCT or whole-brain radiotherapy improves outcomes but is often limited by patient factors. Maintenance therapies such as BTK inhibitors and lenalidomide have emerged to prolong remission and reduce relapse risk, especially in elderly or ASCT-ineligible patients. Both agents penetrate the blood-brain barrier and have shown efficacy in relapsed/refractory PCNSL, but their role as frontline maintenance remains underexplored.

Data Highlights

Key Findings

• BTK inhibitors and lenalidomide both penetrate the blood-brain barrier and target key survival pathways in PCNSL.
• Maintenance therapy with BTKis or lenalidomide initiated after induction and consolidation can prolong remission and reduce early relapse risk.
• BTKis (ibrutinib, zanubrutinib, orelabrutinib) were administered continuously at specified doses without switching during maintenance.
• Lenalidomide was given in 28-day cycles with 21 days on treatment and 7 days off to allow bone marrow recovery.
• Both agents were generally well tolerated with manageable toxicity profiles in the maintenance setting.
• Maintenance therapy choice was individualized based on patient response, tolerance, and socioeconomic factors.

Clinical Implications

For patients with newly diagnosed PCNSL achieving remission after induction, maintenance therapy with BTK inhibitors or lenalidomide offers a viable strategy to sustain durable responses, especially when ASCT is not feasible. Clinicians should consider patient-specific factors including tolerance and access when selecting maintenance agents. Regular monitoring with MRI and CSF analysis is essential to assess response and detect progression during maintenance.

Conclusion

BTK inhibitors and lenalidomide represent promising frontline maintenance options in PCNSL, potentially improving long-term outcomes with acceptable safety profiles. Further prospective studies are warranted to optimize maintenance strategies and confirm survival benefits.

References

1. NCCN Guidelines 2022 -- Primary CNS Lymphoma
2. Wang et al. 2023 -- BTK Inhibitors in PCNSL
3. Li et al. 2022 -- Lenalidomide Maintenance in PCNSL