Anti-PD1/PDL1 induced psoriasis

BackgroundImmune checkpoint inhibitors are novel agents approved for the treatment of late-stage malignancies. Despite its important clinical benefits, checkpoint inhibition is associated with a unique spectrum of side effects known as immune-related adverse events. Skin toxicities are the most frequent immune-related adverse events during anti-PD1 blockade therapies. Among them, rare cases of psoriasis exacerbation have been reported.MethodsWe present the clinical characteristics of exacerbated psoriasis in 5 patients under anti-PD1/PDL1 therapy.ResultsA total of 5 patients were overall included (4 males, 1 female mean age 65.8 years). Among them, 3 were diagnosed with nonsmall cell lung cancer, 1 with papillary urothelial carcinoma, and 1 with squamous cell carcinoma of the tonsil. Of all, 3 patients were treated with anti-PD1 (1 with pembrolizumab, 2 with nivolumab), whereas the remaining 2 with anti-PDL1 (durvalumab). Only 1 out of 5 patients had active psoriatic lesions at the time of treatment initiation, 2 shared a past history of psoriasis, and 1 reported a strong related family history (3/5 siblings). Four out of 5 patients experienced guttate lesions, though the most severe exacerbation was noted in the durvalumab group. Four out of 5 patients managed to continue treatment after close dermatologic monitoring, whereas 1 patient under durvalumab was forced to treatment delays owing to the severity of the skin reactions. Skin rashes appeared in all patients after the fourth cycle of immunotherapy.ConclusionsBoth anti-PD1 and anti-PDL1 therapies can lead to psoriasis exacerbation although more severe flares were noted in patients treated with durvalumab. Not only personal but also related family history of psoriasis are significant risk factors and need to be outlined before treatment initiation. If such related history exists, strict skin surveillance can lead to the early diagnosis and treatment of any psoriatic exacerbations that could otherwise severely affect quality of life or even compromise therapeutic protocols and final prognosis.     

Pembrolizumab for the first-line treatment of non-small cell lung cancer

Introduction: Platinum-based chemotherapy had long played a role as standard therapy for the first-line treatment of advanced or recurrent non-small cell lung cancer (NSCLC). However, immune checkpoint inhibitors such as pembrolizumab, a monoclonal antibody that prevents programmed death protein 1 (PD-1) receptor, have brought a paradigm shift in this field.

Areas covered: In this article, we review the relevant literatures and ongoing trials on the first-line treatment of pembrolizumab. Especially, in two pivotal phase III trials, KEYNOTE-024 and ?189, both pembrolizumab monotherapy and combined pembrolizumab plus chemotherapy significantly prolonged overall survival (OS) compared to the existing platinum-based chemotherapy. Currently, multiple trials with combination therapy of pembrolizumab and other agents have been conducted, and further evidences are expected to be created.

Expert opinion: Immune checkpoint inhibitors that block the PD-1/PD-L1 pathway are essential drugs for advanced or recurrent NSCLC, among which pembrolizumab becomes one of the standards of care in the first-line of NSCLC. For further improvement in efficacy of pembrolizumab, it is necessary to clarify the identification of biomarkers exclusive to PD-L1 expression, predictive factors for patients who benefit most from the agent.     

Ipilimumab alone or in combination with nivolumab after progression on anti-PD-1 therapy in advanced melanoma

BackgroundThe anti-programmed cell death-1 (PD-1) inhibitors pembrolizumab and nivolumab alone or in combination with ipilimumab have shown improved objective response rates and progression-free survival compared to ipilimumab only in advanced melanoma patients. Anti-PD-1 therapy demonstrated nearly equal clinical efficacy in patients who had progressed after ipilimumab or were treatment-naïve. However, only limited evidence exists regarding the efficacy of ipilimumab alone or in combination with nivolumab after treatment failure to anti-PD-therapy.Patients and methodsA multicenter retrospective study in advanced melanoma patients who were treated with nivolumab (1 or 3 mg/kg) and ipilimumab (1 mg or 3 mg/kg) or ipilimumab (3 mg/kg) alone after treatment failure to anti-PD-1 therapy was performed. Patient, tumour, pre- and post-treatment characteristics were analysed.ResultsIn total, 47 patients were treated with ipilimumab (ipi-group) and 37 patients with ipilimumab and nivolumab (combination-group) after treatment failure to anti-PD-1 therapy. Overall response rates for the ipi- and the combination-group were 16% and 21%, respectively. Disease control rate was 42% for the ipi-group and 33% for the combination-group. One-year overall survival rates for the ipi- and the combination-group were 54% and 55%, respectively.ConclusionsIpilimumab should be considered as a viable treatment option for patients with failure to prior anti-PD-1 therapy, including those with progressive disease as best response to prior anti-PD-1. In contrast, the combination of ipilimumab and nivolumab appears significantly less effective in this setting compared to treatment-naïve patients.     

帕博利珠单抗治疗早期三阴性乳腺癌患者的安全性系统评价

目的 通过Meta分析评估帕博利珠单抗（pembrolizumab）治疗早期三阴性乳腺癌（ETNBC）的安全性。方法 计算机检索PubMed、Web of science、Cochrane数据库、Embase、clinicaltrials.gov、中国知网、万方和CBM,收集传统化疗联合帕博利珠单抗（试验组）对比传统化疗联合安慰剂（对照组）或紫杉醇联合帕博利珠单抗（试验组）对比紫杉醇联合安慰剂（对照组）的临床试验,检索时间为从建库至2023年4月1日。筛选文献、提取数据和评价质量后,采用RevMan 5.3软件进行统计分析、敏感性分析。结果 共纳入3篇文献,合计1 509例患者,试验中结局指标（即3～5级不良事件）主要为腹泻、中性粒细胞减少、贫血、疲乏和皮肤反应。Meta分析结果显示,试验组患者3～5级腹泻（RR=1.83, 95%CI:0.81～4.12, P=0.15）、中性粒细胞减少症（RR=1.03, 95%CI:0.88～1.20, P=0.73）、贫血（RR=1.20, 95%CI:0.92～1.55, P=0.18）、皮肤反应（RR=3.14, 95%CI:0.28～35...     

Cutaneous,gastrointestinal, hepatic,endocrine, and renal side-effects of anti-PD-1 therapy

BackgroundAnti-programmed cell death receptor-1 (PD-1) antibodies represent an effective treatment option for metastatic melanoma as well as for other cancer entities. They act via blockade of the PD-1 receptor, an inhibitor of the T-cell effector mechanisms that limit immune responses against tumours. As reported for ipilimumab, the anti-PD-1 antibodies pembrolizumab and nivolumab can induce immune-related adverse events (irAEs). These side-effects affect skin, gastrointestinal tract, liver, endocrine system and other organ systems. Since life-threatening and fatal irAEs have been reported, adequate diagnosis and management are essential.Methods and findingsIn total, 496 patients with metastatic melanoma from 15 skin cancer centers were treated with pembrolizumab or nivolumab; 242 side-effects were described in 138 patients. In 116 of the 138 patients, side-effects affected the skin, gastrointestinal tract, liver, endocrine, and renal system. Rare side-effects included diabetes mellitus, lichen planus, and pancreas insufficiency due to pancreatitis.ConclusionAnti-PD1 antibodies can induce a plethora of irAEs. The knowledge of them will allow prompt diagnosis and improve the management resulting in decreased morbidity.