Lutz Mathias, Schulze Arik B, Rebber Elisabeth, Wiebe Stefanie, Zoubi Tarek, Grauer Oliver M, Keßler Torsten, Kerkhoff Andrea, Lenz Georg, Berdel Wolfgang E
Department of Medicine A, University Hospital of Münster, Münster, Germany.
Department of Internal Medicine, Marienhospital Osnabrück, Osnabrück, Germany.
Cancer Res Treat. 2017 Apr;49(2):548-552. doi: 10.4143/crt.2016.110. Epub 2016 Jul 12.
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.
进行性多灶性白质脑病（PML）是一种几乎仅在免疫功能低下患者中出现的毁灭性神经系统疾病。最近，诸如利妥昔单抗等显著抑制免疫系统的单克隆抗体的应用导致PML病例增加。尽管基于利妥昔单抗的免疫化学疗法仍然是慢性淋巴细胞白血病（CLL）的标准治疗方法，但诸如伊布替尼等布鲁顿酪氨酸激酶抑制剂的重要性正在稳步增加。然而，关于这些新物质可能的副作用的长期经验却很少见。在此，我们报告了在包括利妥昔单抗在内的多条先前治疗线后，最终致命的PML可能与伊布替尼治疗CLL相关的情况。据我们所知，这是第一项报告此类发现的研究。由于最后一次利妥昔单抗疗程是在3年多前应用的，可以推测伊布替尼对B细胞的强烈抑制导致了PML。随着对这种潜在副作用认识的提高，进一步的临床研究当然有必要评估这种可能的关联。
