scholarly journals Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: a prospective study

2020 ◽  
Vol 8 (2) ◽  
pp. e000779 ◽  
Author(s):  
Tomoko Kobayashi ◽  
Shintaro Iwama ◽  
Yoshinori Yasuda ◽  
Norio Okada ◽  
Takayuki Okuji ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malignant Melanoma ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Pituitary Dysfunction ◽  
Pituitary Enlargement

BackgroundSeveral immune-related adverse events (irAEs) are reported to be associated with therapeutic efficacy of immune checkpoint inhibitors, yet whether pituitary dysfunction, a life-threatening irAE, affects overall survival (OS) in patients with malignancies is unclear. This prospective study examined the association of pituitary dysfunction (pituitary-irAE) with OS of patients with non-small cell lung carcinoma (NSCLC) or malignant melanoma (MM).MethodsA total of 174 patients (NSCLC, 108; MM, 66) treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab at Nagoya University Hospital were evaluated for OS and the development of pituitary-irAE. Kaplan-Meier curves of OS as a function of the development of pituitary-irAE were produced with the log-rank test as a primary endpoint.ResultsPituitary-irAE was observed in 16 patients (4 (3.7%) with NSCLC, 12 (18.2%) with MM) having two different disease types: hypophysitis with deficiency of multiple anterior pituitary hormones accompanied by pituitary enlargement, and isolated adrenocorticotropic hormone (ACTH) deficiency without pituitary enlargement. Among these patients, 6 developed pituitary-irAE while being treated with ipilimumab (6/25 patients (24.0%) treated with ipilimumab) and 10 developed pituitary-irAE during treatment with nivolumab or pembrolizumab (10/167 (6.0%)). All 16 patients had ACTH deficiency and were treated with physiological doses of hydrocortisone. The development of pituitary-irAE was associated with better OS in patients with NSCLC (not reached vs 441 (95% CI not calculated) days, p<0.05) and MM (885 (95% CI 434 to 1336) vs 298 (95% CI 84 to 512) days, p<0.05).ConclusionsIn our study cohort, the incidence of pituitary-irAE was higher than previously reported and the development of pituitary-irAE predicted better prognosis for both NSCLC and MM when patients were treated with physiological doses of hydrocortisone.Clinical trials registrationUMIN000019024.

scholarly journals Challenges of Immunotherapy in Stage IV Non–Small-Cell Lung Cancer

2021 ◽  
pp. OP.20.00949
Author(s):  
Sophie Stock-Martineau ◽  
Kate Magner ◽  
Kevin Jao ◽  
Paul Wheatley-Price
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Programmed Death

Treatment for metastatic non–small-cell lung carcinoma has seen important advances in recent years with the introduction of targeted therapies and immunotherapy. Immune checkpoint inhibitors, which target the programmed death 1 receptor and programmed death ligand-1, alone or in combination with platinum-based chemotherapy, have become standard of care in the first-line setting for patients with advanced non–small-cell lung carcinoma without targetable driver mutations. However, several clinical questions have now since emerged. Physicians treating lung cancer lack guidance when treating patients who have a poor performance status, patients who are receiving corticosteroids, and those known for pre-existing autoimmune disorders. Furthermore, data are scarce on rechallenging a patient with immune checkpoint inhibitors after the occurrence of a significant immune-related adverse event. In this review, we aim to shed light on these topics.

scholarly journals Immune checkpoint inhibitors for the management of advanced non–small-cell lung carcinoma

2020 ◽  
Vol 31 (6) ◽  
pp. 637-645 ◽  
Author(s):  
Li-ting Lai ◽  
Zheng-yu Zhan ◽  
Miao Feng ◽  
Fan Li ◽  
Lin-feng Lai ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

Utilization of novel highly multiplexed immunofluorescence microscopy technology to understand immunological tumor microenvironments in small cell lung carcinoma patients receiving combination PD-L1 and PARP inhibition therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14289-e14289 ◽  
Author(s):  
Christopher Julius Trindade ◽  
Elizabeth McDonough ◽  
Jeffery Hanson ◽  
Beatriz Walter Rodriguez ◽  
Nitin Roper ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Immune Response ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Cd8 T Cell ◽  
Small Cell ◽  
Cell Tumor ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

e14289 Background: Immune checkpoint inhibitors have changed the way we treat most malignant tumors especially lung carcinomas. While PD-L1 is the only FDA approved companion diagnostic used to predict response, its accuracy and specificity is lacking. Thus, new biomarkers and mechanisms of checkpoint inhibitor need to be elucidated. A major limitation with the current approved method, immunohistochemistry, is that it can typically only measure one parameter per tissue section. Currently new multiplexing microscopy techniques are being developed that allow us to see multiple parameters at the cell level, which can answer new questions regarding tumor immune microenvironments (TIME). In this study we used a novel multiplexed immunofluorescent (MxIF) microscopy technique, Cell DIVE™ (GE Healthcare, Issaquah, WA), to analyze formalin fixed paraffin embedded (FFPE) tissue samples from small cell lung carcinoma (SCLC) patients treated with a PD-L1 inhibitor, durvalumab (MEDI4736), in combination with a PARP inhibitor, olaparib. Methods: Biopsies from patients enrolled in a phase II expansion cohort clinical trial (NCT02484404) treated with durvalumab and olaparib were analyzed. Tumor immune response from a cohort of 3 responders and 3 non-responders, before and after treatment, underwent MxIF analysis using biomarkers including CD3, CD4, CD8, CD20, CD39, CD45RA, CD45RO, CD56, CD57, CD103, FOXP3, GATA3, LAMP1, PD-L1 and T-bet. Our panel was able to effectively discern T-cells (including subsets, maturation, and function), B-cells, and NK cells and their interaction with tumor cells. The results were validated for accuracy and consistency using immunohistochemistry and Vectra Polaris Imaging System. Results: Spatial analysis of TIME showed responders (3/3) were associated with an inflamed CD8+ T-cell tumor microenvironment while non-responders (3/3) displayed an excluded or desert CD8+ T-cell tumor microenvironment. MxIF/Cell DIVE™ allowed us to further characterize the immune response. Conclusions: Analyzing the type and pattern of immune response using multiplexed immunofluorescent and single cell characterization microscopy may better predict prognosis than PD-L1 immunohistochemistry in SCLC patients treated with immune checkpoint inhibitors. Clinical trial information: NCT02484404.

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