Is rituximab (Rituxan, generic name: rituximab) associated with neurotoxicity?

From the Guidelines

Rituximab is associated with a low risk of neurotoxicity, and the most significant concern is peripheral neuropathy, which can be mitigated by using subcutaneous administration and once-weekly dosing of bortezomib when used in combination with rituximab. The evidence from recent studies, including the 2024 NCCN guidelines 1, suggests that rituximab can cause neurotoxicity, although it is relatively uncommon. The most significant neurological adverse effects associated with rituximab include progressive multifocal leukoencephalopathy (PML), posterior reversible encephalopathy syndrome (PRES), encephalitis, peripheral neuropathy, and rarely, acute neurotoxicity presenting as headache, vision changes, or altered mental status.

Key Points to Consider

• The mechanism behind rituximab-associated neurotoxicity relates to its B-cell depleting effects, which can compromise immune surveillance in the central nervous system and potentially allow for viral reactivation or immune-mediated processes 1.
• Patients with pre-existing neurological conditions or those receiving concomitant immunosuppressive therapy may be at higher risk of neurotoxicity 1.
• Clinicians should monitor patients for new or worsening neurological symptoms during and after rituximab treatment, as early recognition and management of these complications is essential 1.
• The use of subcutaneous administration and once-weekly dosing of bortezomib can reduce the risk of peripheral neuropathy when used in combination with rituximab 1.

Recommendations for Clinical Practice

• Monitor patients for signs of neurotoxicity, including peripheral neuropathy, during and after rituximab treatment 1.
• Use subcutaneous administration and once-weekly dosing of bortezomib when used in combination with rituximab to reduce the risk of peripheral neuropathy 1.
• Consider the risk of neurotoxicity when selecting a treatment regimen for patients with Waldenström's macroglobulinemia, and choose regimens that minimize this risk whenever possible 1.

From the Research

Association of Rituximab with Neurotoxicity

• Rituximab is a monoclonal antibody used in the treatment of various lymphoid malignancies and autoimmune disorders 2.
• While rituximab is generally well-tolerated, there have been reports of serious adverse events, including neurotoxicity 3, 4.
• A case study reported a patient with rheumatoid arthritis on rituximab therapy who developed methotrexate-induced leukoencephalopathy, a rare form of neurotoxicity 3.
• Another case study reported a patient with follicular lymphoma who developed encephalopathy after treatment with rituximab and bendamustine, suggesting a possible rare side effect of bendamustine neurotoxicity 5.
• A review of serious adverse events associated with rituximab highlighted the importance of critical care in managing complications, including neurotoxicity 4.
• A practical review of rituximab in neurological disease discussed the principles, evidence, and practice of using rituximab in neuroinflammatory disorders, including its safety profile and potential neurotoxicity 6.

Mechanisms and Risk Factors

• The exact mechanisms of rituximab-induced neurotoxicity are not fully understood, but may involve the depletion of B cells and the disruption of the blood-brain barrier 4, 6.
• Risk factors for neurotoxicity with rituximab may include concomitant use of other medications, such as methotrexate or bendamustine, and pre-existing neurological conditions 3, 5, 4.

Clinical Implications

• Clinicians should be aware of the potential for neurotoxicity with rituximab and monitor patients closely for signs and symptoms of neurological adverse events 3, 4, 6.
• The use of rituximab in neurological disorders requires careful consideration of the potential benefits and risks, as well as close monitoring and management of potential complications 6.