Enteric plexus neuropathy associated with PD-L1 blockade in a patient with small-cell lung cancer

Immunotherapy ◽  
2021 ◽  
Author(s):  
Ioannis P Trontzas ◽  
Vasiliki E Rapti ◽  
Nikolaos K Syrigos ◽  
George Kounadis ◽  
Nikoleta Perlepe ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Autonomic Neuropathy ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Enteric Plexus

Immune checkpoint inhibitors have revolutionized the management of patients with cancer. The increasing use of these agents has brought up a new set of adverse events which are widely heterogenous and potentially life-threatening. Rare immune-related adverse events associated with nervous system have not been described thoroughly, but their early recognition and management may be crucial. Immune-related autonomic neuropathy may be presented with a constellation of symptoms ranging from gastrointestinal and urinary complaints, to sweating and hypotension. Intestinal pseudo-obstruction as consequence of immune-related myenteric autonomic neuropathy is an under-recognized, not-well described and potentially fatal adverse event. We herein, present a unique case of enteric plexus neuropathy induced by PD-L1 blockade in a patient with small-cell lung cancer.

Panuveitis in patient on ipilimumab/nivolumab combination for small-cell lung cancer treated with an intravitreal dexamethasone implant

2020 ◽  
pp. 107815522096979
Author(s):  
Jade L Hefler ◽  
Lauren M Bailey ◽  
Cynthia El Rahi ◽  
Amy C Schefler ◽  
Eric H Bernicker
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Checkpoint Inhibitors ◽  
Early Recognition ◽  
Small Cell ◽  
Small Cell Lung ◽  
Antitumor Effects ◽  
Serious Adverse Events

Background Immunotherapy with checkpoint inhibitors has demonstrated durable responses and remarkable antitumor effects in a variety of cancers. Although these agents are generally well-tolerated, patients can experience immune-related adverse events (irAEs) that require prompt recognition by healthcare providers. Immune-related ocular toxicities are rare, but serious adverse events have been reported with the use of checkpoint inhibitors. Case presentation: Here, we describe a rare case of panuveitis during Nivolumab and Ipilimumab combination treatment in a patient being treated for recurrent Small Cell Lung Cancer (SCLC). The patient was managed with an injection of Ozurdex (Allergan, Madison, NJ), a dexamethasone intravitreal implant. The patient had a resolution of inflammation and an improvement in her vision and was able to resume nivolumab monotherapy without recurrence of the panuveitis. Conclusion This case highlights the importance of early recognition of ocular irAEs by ocular oncologists and the successful approach to treatment of immunotherapy-induced panuveitis in order to avoid permanent cessation of therapy.

scholarly journals 803 Immune-related adverse events correlate with improved outcomes in patients with advanced non-small cell lung cancer treated with combinations of immune-checkpoint inhibitors and chemotherapy

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A840-A840
Author(s):  
Lindsey Shantzer ◽  
Sean Dougherty ◽  
Wendy Novicoff ◽  
John Melson ◽  
Daniel Reed ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung

BackgroundImmune checkpoint inhibitors (ICIs) have become the backbone of treatment for most driver-mutation negative, advanced non-small cell lung cancers. ICIs have been approved both as monotherapy and in combination with chemotherapy for front line management. While ICIs are generally regarded as well-tolerated, an unintended activation of the immune system can result in a variety of immune-related adverse events (irAEs), which can limit their use in severe cases. In patients with NSCLC treated with ICI monotherapy, the occurrence of an irAE and the development of multisystem irAEs have been associated with improved clinical outcomes, suggesting irAE occurrence could have prognostic implications.1–4 However, in patients treated with combination immunotherapy plus chemotherapy, the correlation between irAEs and survival has not been completely elucidated.MethodsWe conducted a retrospective chart review of 94 patients with advanced NSCLC treated with a combination of ICI plus chemotherapy between 2015 and 2021 to evaluate for a correlation between irAE occurrence and overall survival (OS). Patients were divided into two groups: those who experienced at least one irAE and those who did not experience an irAE. To account for immortal time bias, we conducted landmark analyses at 12 and 24 weeks. We additionally investigated the impact of multisystem irAEs on clinical outcomes and described the profile of irAEs observed at our institution.ResultsAmong the 94 evaluable patients identified in our population, 43.6% experienced at least one irAE. Of those patients who experienced an irAE, 26 (63.4%) experienced a single irAE, 9 (22.0%) experienced 2 irAEs, and 6 (14.6%) experienced 3 or more irAEs. The most commonly observed irAEs were dermatitis followed by pneumonitis and colitis. In our cohort, patients with at least one irAE had significantly longer median OS (16.8 mos vs 9.8 mos) compared to those who did not experience an irAE (HR 0.51, 95% CI 0.43–0.76, p=0.011) (figure 1). Landmark survival analyses at 12 and 24 weeks continued to support significant differences in median OS based on presence or absence of an irAE (HR 0.49, 95% CI 0.24–0.46, and HR 0.45, 95% CI 0.21–0.60 respectively). Among patients with at least one irAE, the subset of patients who experienced multiple irAEs had further improved median OS compared to those with a single irAE.ConclusionsIn patients with advanced NSCLC treated with combination ICI plus chemotherapy, the occurrence of an irAE is associated with improved overall survival.ReferencesTeraoka S, Fujimoto D, Morimoto T, et al. Early Immune-related adverse events and association with outcome in advanced non-small cell lung cancer patients treated with Nivolumab: a prospective cohort study. Journal of Thoracic Oncology : Official Publication of the International Association for the Study of Lung Cancer 2017;12(12):1798–1805. doi:10.1016/j.jtho.2017.08.022.Ricciuti B, Genova C, De Giglio A, et al. Impact of immune-related adverse events on survival in patients with advanced non-small cell lung cancer treated with nivolumab: long-term outcomes from a multi-institutional analysis. Journal of Cancer Research and Clinical Oncology 2019;145(2):479–485. doi:10.1007/s00432-018-2805-3.Toi Y, Sugawara S, Kawashima Y, et al. Association of immune-related adverse events with clinical benefit in patients with advanced non-small-cell lung cancer treated with nivolumab. The Oncologist. 2018;23(11):1358–1365. doi:10.1634/theoncologist.2017-0384.Shankar B, Zhang J, Naqash AR, et al. Multisystem immune-related adverse events associated with immune checkpoint inhibitors for treatment of non-small cell lung cancer. JAMA Oncol 2020;6(12):1952–1956. doi:10.1001/jamaoncol.2020.5012Ethics ApprovalThis research study obtained ethics approval by the institutional review board at the University of Virginia, IRB# 19083.Abstract 803 Figure 1Overall Survival by presence or absence of an irAE in patients with advanced lung cancer treated with immune checkpoint inhibitors plus chemotherapy

Immune-related adverse events and outcomes during treatment with immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21662-e21662
Author(s):  
Javier López Gallego ◽  
Pablo Ayala de Miguel ◽  
Itziar Gorospe García ◽  
Pablo René Rivera Vargas ◽  
Andrea Posada Restrepo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cox Regression ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung

e21662 Background: Immunotherapy of cancer has changed the paradigm of treatment of many tumours, specially non-small cell lung cancer (NSCLC). The use of immune-checkpoint inhibitors (ICI) is associated in some patients with the development of new immune-related adverse events (irAEs). Our aim was to study if there is any correlation between the appearence of irAEs and the efficacy of ICI. Methods: We collected data of 104 patients diagnosed of advanced NSCLC and treated with ICI in monotherapy at our institution between December 2015 and December 2019. Several variables as clinical, tumour-related and therapeutical were included and univariate and multivariate Cox regression analysis were performed. Results: Cohort of 84 men and 20 women, median age of 67 years and 86% with Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1. 89% were active or ex-smokers and 11% had never smoked. 60% of patients had adenocarcinoma histology, 39% scamous and 1% had not otherwise specified (NOS) carcinoma histology. 3% of patients had III-B stage at the moment of start of immunotherapy, 37% M1a, 30% M1b and 30% M1c. 2 patients had driver mutations in EGFR gene. 41% of patients had unknown PDL1 status; 14% had no PDL1 expression, 14% low expression and 31% high expression. 78% of patients had progressed to prior line of treatment, while 22% were treatment-naive. irAEs occured in 65% of patients; 12% developed grade 3 to 4 toxicities. More frequent irAEs were fatigue (54%) and rash (27%). Significant statistical variables in univariate analysis were included in multivariate analysis by Cox regression. The appearence of any grade of iRAE was associated with improved progression-free survival (PFS) (median 17.9 months vs 5.1 months; HR 7.12; p = 0.008). Those patients who experimented any grade of irAE were more likely to achieve stabilization or response than those who suffered progression of disease (HR 13.00; p < 0.001; 95% CI [3.47-48.78]. The use of corticosteroids during treatment with ICI was not related to the benefit of treatment. Conclusions: Appearence of immune-related adverse effects during treatment with ICI was associated with better outcomes in our population. The use of corticosteroids during immunotherapy didn´t have any deleterious effect on the efficacy of treatment.

A phase II study of vorolanib in combination with toripalimab in patients with non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21053-e21053
Author(s):  
Jun Zhao ◽  
Jianjie Li ◽  
Hanxiao Chen ◽  
Xue Yang ◽  
Jia Zhong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Phase Ii ◽  
Cell Lung Cancer ◽  
Phase Ii Study ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Nsclc Patients

e21053 Background: VEGF promotes an immunosuppressive microenvironment and contributes to resistance of immune checkpoint inhibitors in cancer treatment. VEGF inhibitors have been shown to enhance efficacy of checkpoint inhibitors in clinical studies. Vorolanib (CM082) is a multi-target tyrosine kinase inhibitor including VEGF, PDGF, c-kit, and Flt-3. Toripalimab (JS001) is a humanized IgG4 mAb against programmed death-1 (PD-1). This phase II study aims to evaluate efficacy and safety of the combination of vorolanib and JS001 in non-small cell lung cancer (NSCLC) patients who progressed with prior first-line standard therapy. Methods: This single-arm, single-center, phase II study (NCT03848611) enrolls NSCLC patients with measurable disease (RECIST 1.1) and Eastern Cooperative Oncology Group performance status ≤ 1, regardless of PD-L1 status. 15 patients received 150 mg oral CM082 daily plus 240 mg intravenous JS001 every 3 weeks while 3 patients received 100 mg oral CM082 daily plus 240 mg intravenous JS001 every 3 weeks until disease progression or intolerable toxicity. The primary endpoint is objective response rate (ORR). Results: Between April 2019 and July 2020, 18 patients were enrolled. Median age was 64 years. 9 of 18 patients (50%) were adenocarcinoma and 9 of 18 patients (50%) were squamous. Males account for 83% (15/18) with 4 non-smokers among the male patients. At the data cutoff (January 11, 2021), we observed 2 (11%) confirmed and 1 (6%) unconfirmed partial response (PR), 6 (33%) stable disease (SD) and 9 (50%, including 2 PR of the target lesions) progression disease (PD). Tumor shrinkage was seen in 6 (33%) of the 18 patients. Two (11%) patients were still on the study drugs. Interestingly, all the patients with confirmed PR or PR of the target lesions were squamous histology. The most common treatment-related adverse events were proteinuria (67%), elevated ALT (60%), elevated AST (53%), hypertension (40%), and increased bilirubin (40%). Grade 3 adverse events include elevated ALT (20%), elevated AST (20%), liver function damage (13%), elevated GGT (7%), fatigue (7%), bellyache (7%), ruptured and infected tumor (7%), and dysphagia (7%). One Grade 4 adverse event was pulmonary embolism. Conclusions: Vorolanib with toripalimab showed a promising antitumor activity with acceptable safety profiles for patients with NSCLC. We hypothesized that the potential benefits of combination therapy for patients with squamous cell carcinoma may be better than those for patients with adenocarcinoma, and the study is ongoing. Clinical trial information: NCT03848611.

Association Between Immune-related Adverse Events and Efficacy of Immune Checkpoint Inhibitors in Non–small-cell Lung Cancer

2019 ◽  
Vol 20 (3) ◽  
pp. 201-207 ◽  
Author(s):  
Mathieu Grangeon ◽  
Pascale Tomasini ◽  
Solene Chaleat ◽  
Arnaud Jeanson ◽  
Maxime Souquet-Bressand ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung
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