Sorbonne Université, Service d'Hématologie Clinique, Hôpital Pitié-Salpêtrière, APHP, 47-83 Bd de l'Hôpital, 75651, Paris Cedex, France.
Sorbonne Université, AP-HP, Hôpital de la Pitié-Salpêtrière, Département de Neurologie, Unité de Médecine Intensive Réanimation Neurologique, and Institut du Cerveau et de la Moelle Épinière, ICM, F-75013, Paris, France.
J Neurol. 2021 Jul;268(7):2458-2465. doi: 10.1007/s00415-021-10414-y. Epub 2021 Jan 30.
Progressive multifocal leukoencephalopathy (PML) is a very rare and opportunistic encephalitis caused by JC polyomavirus that is linked to profound immunosuppression and is usually fatal unless immune function can be restored. Immune checkpoint inhibitors (ICI) are monoclonal antibodies (mAbs) that block either CTLA-4 or PD-1 inhibitor receptors, thus enhancing antiviral T-cell activity. Successful treatment of PML by ICI has recently generated some enthusiasm in case reports/small series of patients. However, the initial enthusiasm was mitigated by some individual case reports that did not show any benefit. More data are thus warranted about efficacy of immune checkpoint inhibitors in the specific context of PML.
We report here the outcomes of six PML patients treated by ICI between 2017 and 2019. Underlying causes of immunosuppression consisted in hematologic malignancies (n = 4), primary immune deficiency (n = 1) and use of immunosuppressive therapies for myasthenia gravis (n = 1). Three patients were alive with a mean follow-up of 21 months (14-33) after first ICI infusion, including one patient with frank clinical response, one with stabilization, and one with initial worsening and further stabilization of PML. The three other patients rapidly died from PML.
Our data suggest that ICI may be effective for PML treatment but were less impressive than the ones previously reported. Larger studies are thus warranted to confirm this efficacy and to identify the predictive factors of response.
进行性多灶性白质脑病（PML）是一种由 JC 多瘤病毒引起的非常罕见的机会性脑炎，与严重的免疫抑制有关，除非免疫功能能够恢复，否则通常是致命的。免疫检查点抑制剂（ICI）是一种单克隆抗体（mAb），可阻断 CTLA-4 或 PD-1 抑制剂受体，从而增强抗病毒 T 细胞活性。最近，ICI 成功治疗 PML 的病例报告/小系列患者引起了一些关注。然而，一些个别病例报告显示没有任何益处，这降低了最初的热情。因此，需要更多的数据来证明免疫检查点抑制剂在 PML 特定情况下的疗效。
我们在此报告了 2017 年至 2019 年间接受 ICI 治疗的 6 例 PML 患者的结果。免疫抑制的潜在原因包括血液系统恶性肿瘤（n=4）、原发性免疫缺陷（n=1）和使用免疫抑制疗法治疗重症肌无力（n=1）。在首次 ICI 输注后，3 名患者存活，平均随访时间为 21 个月（14-33 个月），其中 1 名患者有明显的临床反应，1 名患者病情稳定，1 名患者 PML 最初恶化后进一步稳定。另外 3 名患者迅速死于 PML。
我们的数据表明，ICI 可能对 PML 的治疗有效，但效果不如之前报道的那么显著。因此，需要更大的研究来证实这种疗效，并确定反应的预测因素。
