Nivolumab-induced exocrine pancreatic insufficiency

2021 ◽  
pp. flgastro-2021-102013
Author(s):  
Anna Jones ◽  
Kay Rodgers ◽  
Debbie Jeffrey ◽  
Waqas I Ali ◽  
HJN Andreyev
Keyword(s):  
Side Effects ◽  
Checkpoint Inhibitor ◽  
Pancreatic Insufficiency ◽  
Death Receptor ◽  
Standard Of Care ◽  
Exocrine Pancreatic Insufficiency ◽  
Gastrointestinal Disorders ◽  
Cancer Management ◽  
Checkpoint Inhibitor Therapy ◽  
Cell Death Receptor

Immune checkpoint inhibition is the standard-of-care for many advanced cancers. Side effects of therapy may prevent optimal treatment of the cancer. Management of side effects is dominated by recommendations derived from oncological, not gastroenterological practice. We report a patient who developed pancreatic insufficiency during checkpoint inhibitor therapy with a programmed cell death receptor 1 inhibitor, nivolumab, which if not diagnosed would have prevented ongoing treatment. This is a problem which affects approximately 1 in 100 patients treated with this agent but is rarely recognised. Gastroenterologists need to be aware of the spectrum of gastrointestinal disorders which occur after immunotherapy to treat cancer.

scholarly journals A CASE OF ACQUIRED GENERALIZED LIPODYSTROPHY ASSOCIATED WITH PEMBROLIZUMAB IN A PATIENT WITH METASTATIC MALIGNANT MELANOMA

2020 ◽  
Vol 6 (1) ◽  
pp. e40-e45 ◽  
Author(s):  
Sara Bedrose ◽  
Christie G. Turin ◽  
Victor R. Lavis ◽  
Sang T. Kim ◽  
Sonali N. Thosani
Keyword(s):  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Subcutaneous Fat ◽  
Death Receptor ◽  
Metastatic Malignant Melanoma ◽  
Unexplained Weight Loss ◽  
Checkpoint Inhibitor Therapy ◽  
To Receive ◽  
Cell Death Receptor

Objective: To describe an unusual immune-related adverse event (irAE), acquired generalized lipodystrophy (AGL), from checkpoint inhibitor therapy in a patient treated with pembrolizumab. Methods: This is a case report of a 67-year-old male with metastatic melanoma who was treated with pembrolizumab. Prior to pembrolizumab, the patient was treated with another immune-checkpoint inhibitor and developed autoimmune hemolytic anemia. After starting pembrolizumab, he developed a scrotal mass consistent with panniculitis and after several subsequent cycles, he developed AGL. Results: Loss of subcutaneous fat, unexplained weight loss in combination with worsening insulin resistance and worsening hypertriglyceridemia after initiation of pembrolizumab were consistent with AGL. Autoimmune disorders and other etiologies were ruled out. Despite this irAE, the patient continued to receive pembrolizumab given stabilization of melanoma with treatment. Conclusion: We report the second case of a patient who developed AGL secondary to pembrolizumab, and the fourth case to report such complication secondary to antiprogrammed cell death receptor-1 inhibitors. As use of checkpoint inhibitors becomes more common to treat several types of cancer, it is vital for clinicians to recognize these rare irreversible complications that are not frequently reported in clinical trials.

scholarly journals Diagnosis, monitoring, and management of adverse events from immune checkpoint inhibitor therapy

2019 ◽  
Vol 27 (S2) ◽  
Author(s):  
O.F. Khan ◽  
J. Monzon
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Early Recognition ◽  
Case Reports ◽  
Standard Of Care ◽  
Health Care Team ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy

Immune checkpoint inhibitor therapy (ICIT) is now standard of care for a variety of cancers in both the metastatic and adjuvant settings. As a result, it is imperative to understand the timing, epidemiology, monitoring, diagnosis, and management of immune related adverse events (irAEs) associated with ICIT. This article reviews specific irAEs by organ system, consolidating recommendations from multiple guidelines and incorporating data from case reports to highlight additional evolving therapeutic options for patients. Managing these adverse events requires early recognition, early intervention, and education of both patients and the multidisciplinary health care team. Given the durable responses observed with ICIT, and the irreversible nature associated with some of these irAEs, further research into management of the sequelae of ICIT is required.

Stevens-Johnson syndrome manifesting late in the course of pembrolizumab therapy

2018 ◽  
Vol 25 (6) ◽  
pp. 1520-1522 ◽  
Author(s):  
Andrew Hwang ◽  
Andrew Iskandar ◽  
Constantin A Dasanu
Keyword(s):  
Cell Death ◽  
Side Effects ◽  
Programmed Cell Death ◽  
Toxic Epidermal Necrolysis ◽  
Death Receptor ◽  
Favorable Outcome ◽  
Stevens Johnson Syndrome ◽  
Erythematous Rash ◽  
Johnson Syndrome ◽  
Cell Death Receptor

Pembrolizumab is a humanized antibody that targets programmed cell death receptor-1. This agent is approved for use in the treatment of several malignancies. While pruritus and papulo-erythematous rash are not uncommon with its use, severe reactions such as Stevens-Johnson syndrome/toxic epidermal necrolysis are very rare. We present herein a case of Stevens-Johnson syndrome occurring in a patient who had previously tolerated pembrolizumab without significant side effects for seven months. Prompt recognition of Stevens-Johnson syndrome/toxic epidermal necrolysis and discontinuation of the offending agent are paramount to ensure a favorable outcome.

Long-term immune-related adverse events after discontinuation of immunotherapy

Immunotherapy ◽  
2021 ◽  
Author(s):  
Karoline Horisberger ◽  
Carmen Portenkirchner ◽  
Andreas Rickenbacher ◽  
Luc Biedermann ◽  
Christoph Gubler ◽  
...  
Keyword(s):  
Side Effects ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Late Onset ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Symptomatic Therapy ◽  
Checkpoint Inhibitor Therapy ◽  
Severe Colitis

Immune checkpoint inhibitors have revolutionized the treatment of various cancers but are notorious for their potential to cause severe side effects. While most side effects occur during ongoing therapy, an increasing number of reports of late onset have emerged. It is also not yet clear how long side effects can last. Resolution is achieved under symptomatic therapy, but the side effects may persist latently. We present a patient case with recurrence of colitis after closure of an ileostomy over 1 year after discontinuation of immune checkpoint inhibitor therapy with nivolumab and pembrolizumab. To the best of our knowledge, no other case with severe colitis still lasting after more than a year of suspension of therapy has yet been reported.

scholarly journals Az onkológiában alkalmazott immuncheckpointgátló terápiák autoimmun mellékhatásai: patogenezis, klinikum és terápia

2019 ◽  
Vol 160 (23) ◽  
pp. 887-895
Author(s):  
Éva Szekanecz ◽  
Zoltán Szekanecz
Keyword(s):  
Side Effects ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Current View ◽  
Immune Mediated ◽  
Underlying Malignancy ◽  
Organ Specific ◽  
Checkpoint Inhibitor Therapy

Abstract: Oncotherapy has been revolutionised by the introduction of immune-checkpoint inhibitors including CTLA4, PD1 and PDL1 inhibitors. Patients with malignant diseases may largely benefit from these therapies, which may result in long-term remission even in the most therapy-resistant tumour types. Differences in the mode of action of the various agents may result in varying side-effect profiles. In addition to organ-specific side-effects, overt autoimmune syndromes may also develop. Our current view of oncotherapy has changed as these mostly immune-mediated side-effects highly differ from those observed previously during the administration of traditional anti-tumour compounds. These side-effects should be carefully characterized and differentiated from infections or the progression of the underlying malignancy. Fortunately, several recent recommendations have become available on the management of immune-mediated adverse events due to checkpoint-inhibitor therapy. Orv Hetil. 2019; 160(23): 887–895.

scholarly journals Mathematical prediction of clinical outcomes in advanced cancer patients treated with checkpoint inhibitor immunotherapy

2020 ◽  
Vol 6 (18) ◽  
pp. eaay6298 ◽  
Author(s):  
Joseph D. Butner ◽  
Dalia Elganainy ◽  
Charles X. Wang ◽  
Zhihui Wang ◽  
Shu-Hsia Chen ◽  
...  
Keyword(s):  
Mathematical Model ◽  
Checkpoint Inhibitor ◽  
Standard Of Care ◽  
Model Parameters ◽  
Advanced Cancer Patients ◽  
Patient Response ◽  
Checkpoint Inhibitor Therapy ◽  
Personalized Oncology ◽  
Physical Interactions ◽  
True Progression

We present a mechanistic mathematical model of immune checkpoint inhibitor therapy to address the oncological need for early, broadly applicable readouts (biomarkers) of patient response to immunotherapy. The model is built upon the complex biological and physical interactions between the immune system and cancer, and is informed using only standard-of-care CT. We have retrospectively applied the model to 245 patients from multiple clinical trials treated with anti–CTLA-4 or anti–PD-1/PD-L1 antibodies. We found that model parameters distinctly identified patients with common (n = 18) and rare (n = 10) malignancy types who benefited and did not benefit from these monotherapies with accuracy as high as 88% at first restaging (median 53 days). Further, the parameters successfully differentiated pseudo-progression from true progression, providing previously unidentified insights into the unique biophysical characteristics of pseudo-progression. Our mathematical model offers a clinically relevant tool for personalized oncology and for engineering immunotherapy regimens.

scholarly journals Nivolumab-Induced Exocrine Pancreatic Insufficiency

2021 ◽  
pp. 1628-1632
Author(s):  
Boudewijn Sweep ◽  
Sofie Wilgenhof ◽  
Sander Anten
Keyword(s):  
Side Effects ◽  
Cd8 T Cells ◽  
Pancreatic Insufficiency ◽  
Exocrine Pancreatic Insufficiency ◽  
High Dose ◽  
Endocrine Dysfunction ◽  
Severe Damage ◽  
Chemotherapy Side Effects ◽  
Dose Prednisone ◽  
Exocrine Dysfunction

Immunotherapy is increasingly gaining applicability for several malignancies. While the survival of several malignancies has dramatically improved, immune-related adverse events (irAEs) can occur and can cause severe damage to patients. Side effects such as colitis are well known nowadays; however, with increased use of immunotherapy, less common side effects should also be addressed. In this article, 2 patients that received nivolumab developed exocrine dysfunction of the pancreas. Endocrine dysfunction has been well known, but exocrine dysfunction is less often described. It is important to be aware of this side effect because it is possibly underdiagnosed. Symptoms often mimic symptoms of malignancy, chemotherapy side effects, or immune-related colitis. Although the exact mechanism is yet to be elaborated, dormant CD8+ T cells are likely to be involved. No known therapy is yet been proven to be effective. More knowledge and research about irAEs will lead to possible therapies that will be effective. Currently, high-dose prednisone is recommended based on expert opinion.

Benefits and Side Effects of Different Vegetable Oil Vectors on Apoptosis, Oxidative Stress, and P2X7 Cell Death Receptor Activation

2007 ◽  
Vol 48 (11) ◽  
pp. 5000 ◽  
Author(s):  
Toihiri Said ◽  
Me´lody Dutot ◽  
Raymond Christon ◽  
Jean-Louis Beaudeux ◽  
Chantal Martin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Side Effects ◽  
Vegetable Oil ◽  
Death Receptor ◽  
Receptor Activation ◽  
Cell Death Receptor
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