Cancer Res Treat.  2017 Apr;49(2):548-552. 10.4143/crt.2016.110.

Progressive Multifocal Leukoencephalopathy after Ibrutinib Therapy for Chronic Lymphocytic Leukemia

• Lutz M
• Schulze AB
• Rebber E
• Wiebe S
• Zoubi T
• Grauer OM
• Keßler T
• Kerkhoff A
• Lenz G
• Berdel WE

• KMID: 2378128
• DOI: http://doi.org/10.4143/crt.2016.110

Abstract

Progressive multifocal leukoencephalopathy (PML) is a devastating neurological disease observed nearly exclusively in immunocompromised patients. Recently, the introduction of monoclonal antibodies significantly inhibiting the immune system such as rituximab has led to an increase in PML cases. Although rituximab-based immunochemotherapy remains the standard of treatment for chronic lymphocytic leukemia (CLL), the importance of Bruton's tyrosine kinase inhibitors such as ibrutinib is steadily increasing. However, long-term experiences regarding possible side effects of these new substances are rare. Here, we report the development of eventually fatal PML possibly associated with ibrutinib therapy for CLL after multiple prior treatment lines, including rituximab. To the best of our knowledge, this is the first study to report such findings. Since the last course of rituximab was applied over 3 years ago, it is conceivable that the strong B cell inhibition by ibrutinib led to PML. With increased awareness of this potential side effect, further clinical studies are certainly warranted to evaluate this possible association.

Keyword

B-Cell chronic lymphocytic leukemia; Ibrutinib; Rituximab; Progressive multifocal leukoencephalopathy; JC virus

MeSH Terms

Antibodies, Monoclonal
Immune System
Immunocompromised Host
JC Virus
Leukemia, Lymphocytic, Chronic, B-Cell*
Leukoencephalopathy, Progressive Multifocal*
Protein-Tyrosine Kinases
Rituximab
Antibodies, Monoclonal
Protein-Tyrosine Kinases
Rituximab

Figure

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  Fig. 1. Cranial magnetic resonance imaging demonstrated asymmetric lesions without mass effect or enhancement of contrast media predominantly located in the right frontal lobe. In 2004, decompressive craniectomy was performed in the patient to treat intracerebral hemorrhage. Sequelae of this neurosurgical procedure can be seen on the right temporoparietal side. The same sagittal section of the brain is shown as T1-weighted (A), T2-weighted (B), and fluid-attenuated inversion recovery (C) images.

Reference

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