scholarly journals Characterizing Immune Checkpoint Inhibitor-Induced Hypophysitis and Obstacles in Diagnosis

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A624-A625
Author(s):  
Jake Johnson ◽  
Dua’A Abdallah ◽  
Anupam Kotwal ◽  
Apar Kishor Ganti ◽  
Whitney Sears Goldner
Keyword(s):  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Serum Cortisol ◽  
Pituitary Hormones ◽  
High Dose ◽  
Pituitary Hormone ◽  
Central Hypothyroidism ◽  
Cell Lung Carcinoma

Abstract Background: Immune checkpoint inhibitors (ICI) are used in the treatment of multiple cancers. ICI-induced endocrinopathies are known side effects of many of these agents due to their immunogenic properties. The primary aim of this single institution analysis was to characterize the population who developed hypophysitis and secondary adrenal insufficiency (AI) related to ICI therapy, and identify diagnostic challenges. Methods: We performed a retrospective cohort study of adult cancer patients who received ICI therapy from 12/1/2012- 12/31/2019. We identified 839 patients who received CTLA-4, PD-1, PDL-1 inhibitors, or a combination during this time. Hypophysitis (H) was defined as low ACTH and low serum cortisol ± other pituitary hormone deficiencies. Results: Sixteen patients (1.9%; 16/839) developed hypophysitis after a median of 7 months from ICI initiation. The underlying cancers included: uroepithelial (1/48; 2.1 %), neuroendocrine (1/10; 10%), melanoma (9/156; 5.8%), renal cell carcinoma (4/74; 5.4%), and non-small cell lung carcinoma (1/247; 0.4%). Four patients were excluded since they had isolated secondary AI due to exogenous steroids. Two patients with hypophysitis also had exogenous steroid usage. However, these patients had central hypothyroidism + secondary AI so were included. The median age at start of ICI was 61.3 years and 57% were males. Patients who developed hypophysitis were younger compared to the non-hypophysitis (NH) patients (median age: 57 years vs. 65 years; p=0.0113). Time from initiation of ICI to death/last follow-up was longer in the H group (20 months vs. 10.8 months; p=.0013). 87.5% of group H as compared to 47.3% of NH were alive at end of data collection (p=0.0008). In the H cohort, 43.8% (7/16) received combination CTLA-4/PD-1 inhibitors, 43.8% (7/16) PD-1 monotherapy, 6.25% (1/16) CTLA-4 monotherapy, and 6.25% (1/16) PD-L1 monotherapy. Forty-six percent (6/13) of group H had radiographic evidence of hypophysitis on MRI that resolved on follow up imaging. Six patients had concurrent thyroiditis, 2/16 had concurrent type 1 diabetes, 9/16 had central hypothyroidism, 1/16 had secondary hypogonadism, and 2/16 had GH deficiency. In 15/16 patients, secondary AI presented as the first endocrinopathy, while one patient presented with central hypothyroidism. Conclusions: Development of hypophysitis following ICI therapy was associated with a longer survival. Deficiencies in multiple pituitary hormones occurred in the majority and non-pituitary endocrinopathies occurred in half the cases. High dose steroid usage can also present as secondary AI, making the diagnosis of ICI induced hypophysitis difficult. Further pituitary evaluation must be conducted to differentiate secondary AI due to exogenous steroids from hypophysitis from ICI therapy.

scholarly journals Immune checkpoint inhibitor related hypophysitis: diagnostic criteria and recovery patterns

2021 ◽  
Author(s):  
Ha Nguyen ◽  
Komal Shah ◽  
Steven G Waguespack ◽  
Mimi I Hu ◽  
Mouhammed Amir Habra ◽  
...  
Keyword(s):  
Adrenal Insufficiency ◽  
Diagnostic Criteria ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
High Dose ◽  
Central Hypothyroidism ◽  
Central Adrenal Insufficiency ◽  
Mri Changes

Data on the diagnosis, natural course and management of immune checkpoint inhibitor (ICI) related hypophysitis (irH) are limited. We propose this study to validate the diagnostic criteria, describe characteristics and hormonal recovery and investigate factors associated with occurrence and recovery of irH. A retrospective study including patients with suspected irH at the University of Texas MD Anderson Cancer Center from 5/2003 to 8/2017 was conducted. IrH was defined as: (1) ACTH or TSH deficiency plus MRI changes or (2) ACTH and TSH deficiencies plus headache/fatigue in the absence of MRI findings. We found that of 83 patients followed for a median of 1.75 years (range 0.6-3), the proposed criteria used at initial evaluation accurately identified 61/62 (98%) irH cases. In the irH group (n=62), the most common presentation were headache (60%), fatigue (66%), central hypothyroidism (94%), central adrenal insufficiency (69%) and MRI changes (77%). Compared with non-Ipilimumab (Ipi) regimens, Ipi has a stronger association with irH occurrence (p=0.004) and a shorter time to irH development (p<0.01). Thyroid, gonadal and adrenal axis recovery occurred in 24%, 58% and 0% patients, respectively. High dose steroids (HDS) or ICI discontinuation were not associated with hormonal recovery. In the non-irH group (n=19), one patient had isolated central hypothyroidism and 6 had isolated central adrenal insufficiency. All remained on hormone therapy at last follow up. We propose a strict definition of irH that identifies the vast majority of patients. HDS and ICI discontinuation is not always beneficial. Long term follow up to assess recovery is needed.

scholarly journals The effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing immune checkpoint inhibitor treatment: a retrospective study

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Hyunho Kim ◽  
Ji Eun Lee ◽  
Sook Hee Hong ◽  
Myung Ah. Lee ◽  
Jin Hyoung Kang ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Clinical Outcomes ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Objective Response ◽  
Progression Free Survival ◽  
Solid Cancer ◽  
Cell Lung Carcinoma ◽  
Antibiotics Use

Abstract Background This study aimed to assess the effect of antibiotics on the clinical outcomes of patients with solid cancers undergoing treatment with immune checkpoint inhibitors (ICIs). Methods The medical records of 234 patients treated with ICIs for any type of solid cancer between February 2012 and May 2018 at the Seoul St. Mary’s Hospital were retrospectively reviewed. The data of patients who received antibiotics within 60 days before the initiation of ICI treatment were analyzed. The patients’ responses to ICI treatment and their survival were evaluated. Results Non-small-cell lung carcinoma was the most common type of cancer. About half of the patients were treated with nivolumab (51.9%), and cephalosporin (35.2%) was the most commonly used class of antibiotics. The total objective response rate was 21%. Antibiotics use was associated with a decreased objective response (odds ratio 0.466, 95% confidence interval [CI] 0.225–0.968, p = 0.040). The antibiotics group exhibited shorter progression-free survival (PFS) and overall survival (OS) than the no antibiotics group (median PFS: 2 months vs. 4 months, p < 0.001; median OS: 5 months vs. 17 months, p < 0.001). In the multivariate analysis, antibiotics use was a significant predictor of patient survival (PFS: hazard ratio [HR] 1.715, 95% CI 1.264–2.326, p = 0.001; OS: HR 1.785, 95% CI 1.265–2.519, p = 0.001). Conclusions The use of antibiotics may affect the clinical outcomes of patients with solid cancers treated with ICIs. Careful prescription of antibiotics is warranted in candidates who are scheduled for ICI treatment. Trial registration Not applicable (retrospective study).

Efficacy of immune checkpoint inhibitors in patients with brain metastasis from NSCLC, RCC, and melanoma.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 214-214 ◽  
Author(s):  
Adam Lauko ◽  
Bicky Thapa ◽  
Xuefei Jia ◽  
Manmeet Singh Ahluwalia
Keyword(s):  
Brain Metastasis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Tertiary Care ◽  
Multivariable Analysis ◽  
Volumetric Analysis ◽  
Cell Lung Carcinoma ◽  
Combination Methods

214 Background: Immune checkpoint inhibitors are revolutionizing the treatment of multiple advanced malignancies, however, there is limited data on the efficacy of immune checkpoint blockade in brain metastasis. We conducted a study to analyze the overall survival (OS) and progression-free survival (PFS) among patients with brain metastasis from Non-Small Cell Lung Carcinoma (NSCLC), Renal Cell Carcinoma (RCC), and Melanoma treated with either Nivolumab, Pembrolizumab, Ipilimumab or a combination. Methods: After IRB approval, we retrospectively evaluated patients with brain metastasis treated at our tertiary care institution from 2011-2017 who underwent immunotherapy and one or more of the following; whole brain radiation therapy (WBRT), surgery, stereotactic radiosurgery (SRS) or systemic chemotherapy. Univariable and multivariable analysis was utilized to analyze OS and PFS. Volumetric analysis to assess treatment response is ongoing. Results: A total of 128 patients were identified with a median age of 60.6 years. 49% of patients were male; 77% of patients had a good (0 or 1) ECOG performance scores at the time of the brain metastasis; 83 patients had supratentorial brain metastasis, 11 had infratentorial and 24 had both. The prevalence of mutations was 34% in NSCLC patients, 58% in melanoma, and 0% in RCC. The median OS from the start of immunotherapy was not reached for RCC and was 17.1 and 28.9 months for Melanoma and NSCLC respectively. Median PFS was 5.9, 6.7 and 3.6 months for RCC, Melanoma, and NSCLC respectively. On multivariable analysis, SRS, sex and the number of cycles of immunotherapy had statistically significant hazard ratios. Conclusions: Immune checkpoint inhibitors are efficacious in the treatment of brain metastasis. Further analysis including response criteria using volumetric analysis is ongoing and final results will be presented at the meeting. [Table: see text]

scholarly journals Immunotherapy in head and neck cancer

2019 ◽  
Vol 65 (2) ◽  
Author(s):  
Mateusz Sikora ◽  
Rafał Becht
Keyword(s):  
Immune System ◽  
Head And Neck ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Systemic Treatment ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Malignant Neoplasms ◽  
Cell Lung Carcinoma ◽  
Positive Effects

Immunotherapy is a method for the systemic treatment of malignant neoplasms. It is based on the abolition of the immunosuppressive effect of cancer cells and is meant to mobilize the host’s immune system to actively combat with the disease. The group of cancers which are closely connected with the immune system includes: melanoma, non-small cell lung carcinoma (NSCLC), renal cancer, colon cancer, Hodgkin’s lymphoma, and head and neck squamous cell carcinoma (HNSCC). Currently, cancer immunotherapy involves treatment with immune checkpoint inhibitors, therapeutic cancer vaccines, oncolytic virotherapy, and monoclonal antibodies. In the case of HNSCC, the most frequently used method is treatment with immune checkpoint inhibitors. An example of an immunological checkpoint is programmed cell death protein-1 (PD-1), which may be activated in the process of carcinogenesis to repeal immune surveillance, favouring the development of neoplasm. The function of immune checkpoint inhibitors is based on abolition of the immunosuppressive influence of cancerous cells. Clinical trials show the positive effects of treating HNSCC with immunotherapy in certain patients. In comparison to standard systemic treatment with chemotherapy, immunotherapy rarely causes treatment-related adverse events (TRAEs). Greater survival and treatment response are factors which encourage the further development of immuno-oncology. In this article, we present a review of literature concerning the use of immunotherapy in the treatment of HNSCC.

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.

Immune checkpoint inhibitors in the treatment of cancer

2021 ◽  
Vol 16 ◽  
Author(s):  
Wissam Zam ◽  
Lina Ali
Keyword(s):  
T Cell Activation ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Research Field ◽  
Cell Lung Carcinoma ◽  
Checkpoint Proteins

Background: Immunotherapy drugs, known as immune checkpoint inhibitors (ICIs), work by blocking checkpoint proteins from binding with their partner proteins. The two main pathways that are specifically targeted in clinical practice are cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death protein 1 (PD-1) that showed potent immune-modulatory effects through their function as negative regulators of T cell activation. Methods: In view of the rapid and extensive development of this research field, we conducted a comprehensive review of the literature and update on the use of CTLA-4, PD-1 and PD-L1 targeted therapy in the treatment of several types of cancer including melanoma, non-small-cell lung carcinoma, breast cancer, hepatocellular carcinoma, hodgkin lymphoma, cervical cancer, head and neck squamous cell carcinoma. Results: Based on the last updated list released on March 2019, seven ICIs are approved by the FDA including ipilimumab, pembrolizumab, nivolumab, atezolizumab, avelumab, durvalumab, and cemiplimab. Conclusion: This review also highlighted the most common adverse effects caused by ICIs and which affect people in different ways.

Overlapping NMDA-R and GFAP antibody autoimmune encephalitis after Nivolumab therapy

2020 ◽  
pp. 10.1212/CPJ.0000000000001008
Author(s):  
Felipe A. Ayala ◽  
Sean C. Dougherty ◽  
William Swift ◽  
David A. Lapides
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Cell Activation ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Small Cell Lung Carcinoma ◽  
Death Receptor ◽  
Autoimmune Encephalitis ◽  
High Dose ◽  
Cell Lung Carcinoma

Immunotherapy represents a rapidly expanding area of cancer treatment. Immune checkpoint inhibitors (ICIs), monoclonal antibodies including those targeting cytotoxic T-lymphocyte associated protein 4 or the programmed cell death receptor-1 (PD-1) axis, function by removing inhibitory signals on T-cell activation 1. While promoting T-cell mediated tumor lysis, ICI’s alter the immune system’s regulatory checkpoints which can lead to a host of immune-related adverse events (irAEs) 2, 3. Here, we describe a patient treated with nivolumab (Opdivo, Bristol-Myers Squibb, Princeton, New Jersey) for non-small-cell lung carcinoma (NSCLC) over two years who developed overlapping n-methyl-D-aspartate receptor (NMDA-R) and glial fibrillary acidic protein (GFAP) antibody associated autoimmune encephalitis (AE)4. His hospital course was further complicated by dysautonomia responsive to high-dose steroids.

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
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