Department of Oncology, Stanford School of Medicine, Stanford, CA, USA.
Neurosurgery Service, Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, 110 Francis Street, Boston, MA, 02215, USA.
J Neurooncol. 2020 Jun;148(2):291-297. doi: 10.1007/s11060-020-03514-8. Epub 2020 Apr 29.
PD-1 Immunotherapy is integral in treating multiple cancers, but has been associated with neurological adverse events (nAEs). Our study was aimed at identifying the clinical spectrum of nAEs associated with pembrolizumab and nivolumab.
We performed an IRB approved single-center retrospective cohort study on patients receiving either pembrolizumab or nivolumab. Patients that developed nAEs within 12 months of treatment were identified. Descriptive statistics were conducted, and differences between groups were analyzed by the Chi-square or t test method.
In total, 649 patients were identified. Seventeen patients (2.6%) developed nAEs. Eight of those were on pembrolizumab and nine were on nivolumab. Average age was 62.1 years. Ten were males and 7 were females. Most patients had melanoma (6, 35.3%). Patients who developed nAEs more frequently had intracranial lesions at initiation of anti PD-1 therapy compared to those who did not develop nAEs (76.5% vs 27.8%; p-value < 0.001). Fifteen patients (88.2%) permanently stopped PD-1 therapy. In 8 patients, treatment termination resolved symptoms attributed to immune checkpoint blockade. The majority of patients developed grade 3 or 4 nAEs (10 patients, 58.8%), and required hospitalization (11 patients, 64.7%). Eight patients died for nAEs referable causes.
Pembrolizumab and nivolumab are associated with the development of nAEs associated with increased risk of permanent discontinuation of treatment, hospitalization, and death. Melanoma patients might be at a particularly high risk of such side effects. Future studies are still required to better assess which patients benefit most from such therapies, while minimizing the risk of complications.
PD-1 免疫疗法是治疗多种癌症的重要手段，但与神经系统不良事件（nAEs）有关。我们的研究旨在确定与 pembrolizumab 和 nivolumab 相关的 nAEs 的临床谱。
我们对接受 pembrolizumab 或 nivolumab 治疗的患者进行了一项经过 IRB 批准的单中心回顾性队列研究。确定了在治疗后 12 个月内发生 nAEs 的患者。进行了描述性统计分析，并通过卡方检验或 t 检验方法分析了组间差异。
总共确定了 649 名患者。17 名患者（2.6%）发生了 nAEs。其中 8 名患者使用 pembrolizumab，9 名患者使用 nivolumab。平均年龄为 62.1 岁。10 名男性，7 名女性。大多数患者患有黑色素瘤（6 例，35.3%）。与未发生 nAEs 的患者相比，开始抗 PD-1 治疗时发生 nAEs 的患者颅内病变更常见（76.5%比 27.8%；p 值<0.001）。15 名患者（88.2%）永久性停止 PD-1 治疗。在 8 名患者中，治疗终止缓解了与免疫检查点阻断相关的症状。大多数患者发生了 3 级或 4 级 nAEs（10 例，58.8%），需要住院治疗（11 例，64.7%）。8 名患者因 nAEs 相关原因死亡。
pembrolizumab 和 nivolumab 与 nAEs 相关，这些 nAEs 增加了永久性停止治疗、住院和死亡的风险。黑色素瘤患者可能面临更高的此类副作用风险。仍需要进一步研究以更好地评估哪些患者从这些治疗中获益最大，同时最大限度地降低并发症风险。
