scholarly journals Secukinumab, Pituitary Enlargement and Panhypopituitarism: Are They Related?

2021 ◽  
Author(s):  
Diogo Ramalho ◽  
André Araújo ◽  
Gustavo Rocha ◽  
Filipa Duarte-Ribeiro
Keyword(s):  
Monoclonal Antibody ◽  
Differential Diagnosis ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Human Monoclonal Antibody ◽  
Pituitary Incidentaloma ◽  
Common Etiology ◽  
Pituitary Enlargement ◽  
Prognostic Implications ◽  
Work Up

Pituitary adenomas represent the most common etiology of hypopituitarism associated with a pituitary enlargement, but other causes have been emerging, namely immune checkpoint inhibitors-induced hypophysitis (ipilimumab, nivolumab and pembrolizumab). Secukinumab is a recently approved human monoclonal antibody used for the treatment of psoriasis, with no know reported cases of hypophysitis. We describe a challenging case of panhypopituitarism in a patient with a pituitary incidentaloma and a timing relationship between secukinumab initiation and the manifestation of clinical features suggestive of hypopituitarism. In such intricate work-up, differential diagnosis should be carefully equated, taking into account the therapeutic and prognostic implications.

scholarly journals Opportunities for using in silico‐based extended dosing regimens for monoclonal antibody immune checkpoint inhibitors

2020 ◽  
Vol 86 (9) ◽  
pp. 1769-1777 ◽  
Author(s):  
Cody J. Peer ◽  
Daniel A. Goldstein ◽  
Jennifer C. Goodell ◽  
Ryan Nguyen ◽  
William D. Figg ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Immune Checkpoint ◽  
In Silico ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Dosing Regimens

scholarly journals Paraneoplastic tubulointerstitial nephritis exacerbated by immune checkpoint inhibitor

2021 ◽  
pp. 239936932110563
Author(s):  
Thomas Paul Scherer ◽  
Karim Alexander Saba ◽  
Raeto Thomas Strebel ◽  
Ariana Gaspert ◽  
Richard Cathomas ◽  
...  
Keyword(s):  
Paraneoplastic Syndrome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tubulointerstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Paraneoplastic Syndromes ◽  
Prior Literature ◽  
Metastasized Renal Cell Carcinoma ◽  
Work Up

Background: With the expanding indications and thus broader use of immune checkpoint inhibitors, clinicians are faced with a new kind of immune-related adverse events. Because of their immune modulating effects, immune checkpoint inhibitors have the potential to worsen autoimmunity in general. Paraneoplastic syndromes can be caused by tumor-induced autoimmune mechanisms. The use of immune-activating substances such as checkpoint inhibitors might lead to exacerbation of paraneoplastic syndromes causing premature discontinuation of the immunotherapy. Case presentation: We report on a 64-year-old patient with metastasized renal cell carcinoma who developed acute kidney failure after cytoreductive nephrectomy. Work-up revealed a paraneoplastic syndrome that caused tubulointerstitial nephritis (TIN). Glucocorticoid therapy successfully reversed the acute kidney injury. However, adjuvant therapy with Nivolumab provoked a flare-up of the paraneoplastic syndrome on two occasions, eventually leading to a treatment discontinuation. Conclusions: Many cases of Nivolumab-induced TIN have been described lately. However, our case demonstrates therapy failure due to a flare-up of a pre-existing paraneoplastic syndrome of the renal cancer. Against this background, it can only be speculated that some of the TIN cases discussed in prior literature might also have been flare-ups of subclinical autoimmunity.

Endocrine adverse events related with immune checkpoint inhibitors: an update for clinicians

Immunotherapy ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 481-510 ◽  
Author(s):  
Maria V Deligiorgi ◽  
Mihalis I Panayiotidis ◽  
Dimitrios T Trafalis
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Clinical Success ◽  
Future Perspective ◽  
Programmed Cell Death 1 ◽  
Diagnostic Work ◽  
Work Up

Designated as scientific breakthrough of current decade, immune checkpoint inhibitors attenuate the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed cell death 1 (PD-1)/ligand 1 (PD-L1) pathways, depriving cancer cells of a key strategy of evasion from immunosurveillance. The reinvigoration of immune response translates into clinical success, inevitably entwined with a novel constellation of immune-related adverse events. The present review dissects the endocrine immune-related adverse events, emphasizing their unique profile featured by unpredictable onset, irreversibility, nonspecific symptoms, wide clinical spectrum and sophisticated diagnostic work-up. Guidelines advocate individualized decision-making process guided by clinicians' judgement. Future perspective should be governed by five principles – prevention, anticipation, detection, treatment, monitoring – aiming to gain the optimal profit diminishing immunotoxicity.

Evaluation of the clinical benefits of immune checkpoint inhibitors in patients with advanced melanoma.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 194-194
Author(s):  
Qiyun Ou ◽  
Yunfang Yu ◽  
Dagui Lin ◽  
Tuping Fu ◽  
Quanlong Gao ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Randomized Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Single Agent ◽  
Advanced Melanoma ◽  
Combination Immunotherapy ◽  
Wild Type ◽  
Clinical Benefits

194 Background: Immune checkpoint inhibitors selection in advanced melanoma is complicated further, with choices among anti-CTLA4 or anti-PD-1 therapeutic antibodies options. We aimed to evaluate the clinical benefits of immune checkpoint inhibitors for discussing evidence-based treatment strategies by a meta-analysis of randomized clinical trials (RCTs) data. Methods: We searched for RCTs investigating immune checkpoint inhibitors in patients with advanced melanoma until September 2017. Hazard ratios (HRs) was estimated for overall survival (OS) and progression-free survival (PFS). The quality of the evidence was evaluated with the GRADE framework. Results: Overall, 18 RCTs including a total of 8,917 patients were identified. Immune checkpoint inhibitors versus placebo or observation prolonged PFS (HR = 0.59, 95% confidence interval (CI) 0.44 to 0.78, P < 0.0001) and OS (HR = 0.77, 95% CI 0.72 to 0.84, P < 0.0001). The combination immunotherapy had significantly higher benefit than monotherapy for PFS (HR = 0.75, 95% CI 0.61 to 0.92, P = 0.005) and OS (HR = 0.70, 95% CI 0.61 to 0.79, P < 0.0001). Treatment with anti-PD-1 monoclonal antibody was associated with improved PFS (HR = 0.61, 95% CI 0.59 to 0.69, P < 0.0001) and OS (HR = 0.66, 95% CI 0.58 to 0.77, P < 0.0001) compared with anti-CTLA-4 monoclonal antibody. According to BRAF status analysis, there was a PFS benefit of immune checkpoint inhibitors versus placebo or observation (mutant, HR = 0.58, 95% CI 0.35 to 0.96, P = 0.035; wild–type, HR = 0.52, 95% CI 0.43 to 0.69, P = 0.001), anti-PD-1 outperformed anti-CTLA-4 checkpoint inhibitor (mutant, PFS HR = 0.64, 95% CI 0.51 to 0.79, P < 0.0001; wild–type, PFS HR = 0.58, 95% CI 0.47 to 0.71, P < 0.0001); and combination compared with single-agent immunotherapy (mutant, HR = 0.38, 95% CI 0.15 to 0.98, P = 0.046; wild–type, HR = 0.40, 95% CI 0.23 to 0.69, P = 0.001). Conclusions: This analysis provides an evidence that immune checkpoint inhibitors enhanced OS and PFS in patients with advanced melanoma, as well as combination immunotherapy and anti-PD-1 monoclonal antibody appear to be clinically beneficial option preference.

scholarly journals Silencing of VEGFR2 by RGD-Modified Lipid Nanoparticles Enhanced the Efficacy of Anti-PD-1 Antibody by Accelerating Vascular Normalization and Infiltration of T Cells in Tumors

Cancers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3630
Author(s):  
Riki Cho ◽  
Yu Sakurai ◽  
Haleigh Sakura Jones ◽  
Hidetaka Akita ◽  
Akihiro Hisaka ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Endothelial Cells ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Lipid Nanoparticles ◽  
Vascular Normalization ◽  
Tumor Endothelial Cells

Despite the promising anticancer effects of immune checkpoint inhibitors, their low objective response rate remains to be resolved; thus, combination therapies have been investigated. We investigated the combination of an anti-programmed cell death 1 (aPD-1) monoclonal antibody with the knockdown of vascular endothelial factor receptor 2 (VEGFR2) on tumor endothelial cells to overcome resistance to immune checkpoint inhibitors and improve the objective response rate. The successful delivery of small interfering RNA to tumor endothelial cells was achieved by RGD peptide-modified lipid nanoparticles composed of a novel, pH-sensitive, and biodegradable ssPalmO-Phe. RGD-modified lipid nanoparticles efficiently induced the knockdown of VEGFR2 in tumor endothelial cells (TECs), which induced vascular normalization. The combination of a PD-1 monoclonal antibody with Vegfr2 knockdown enhanced CD8+ T cell infiltration into tumors and successfully suppressed tumor growth and improved response rate compared with monotherapy. Our combination approach provides a promising strategy to improve therapeutic outcomes in immune checkpoint inhibitor-resistant cancers.

Immunotherapy-induced autoimmune hypophysitis

2017 ◽  
Vol 25 (1) ◽  
pp. 217-220 ◽  
Author(s):  
Gautam Valecha ◽  
Manisha Pant ◽  
Uroosa Ibrahim ◽  
Jean P Atallah
Keyword(s):  
Adverse Event ◽  
Checkpoint Inhibitors ◽  
Oral Intake ◽  
Resonance Imaging ◽  
Small Cell Lung ◽  
Autoimmune Hypophysitis ◽  
Extensive Stage ◽  
Pituitary Enlargement ◽  
Diagnostic Work ◽  
Work Up

Autoimmune hypophysitis is an immune-related adverse event of immune checkpoint inhibitors. In this article, we present the case of a 58-year-old female patient who presented to the emergency room with gradually worsening nonspecific symptoms of headache, nausea, vomiting and decreased oral intake of one week duration. The patient had been diagnosed with relapsed extensive stage small cell lung cancer. She was being treated with a combination of ipilimumab and nivolumab after progression on chemotherapy. Gadolinium-enhanced magnetic resonance imaging of head revealed pituitary enlargement up to 1.5 cm and pituitary stalk enlargement up to 4 mm consistent with hypophysitis. The patient was treated with corticosteroids resulting in rapid resolution of her symptoms. The objective of our report is to highlight this rare but important adverse event associated with checkpoint inhibitors, and discuss its clinical features, diagnostic work-up and treatment.

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.

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