scholarly journals Acute kidney injury from immune checkpoint inhibitor use

2019 ◽  
Vol 12 (10) ◽  
pp. e231211 ◽  
Author(s):  
Lexis Gordon ◽  
Pouneh Dokouhaki ◽  
Kimberly Hagel ◽  
Bhanu Prasad
Keyword(s):  
Acute Kidney Injury ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Programmed Death ◽  
Programmed Death 1

Immune checkpoint inhibitors are novel oncological medications, current classes of which include monoclonal antibodies that target inhibitory receptors cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), programmed death 1 protein (PD-1) and programmed death-ligand 1. While they are novel in their ability to treat cancer, they also have a unique spectrum of immune-related adverse events. Renal-related immune adverse events, though rare, are an increasingly recognised clinical entity. We present the case of a 67-year-old man with acute kidney injury (AKI) after the second cycle of combination anti-CTLA-4 and anti-PD-1 antibodies for metastatic cutaneous melanoma. He presented with vomiting and diarrhoea, and AKI secondary to dehydration was treated with aggressive rehydration. After failing to recover biochemically, a renal biopsy was performed, which demonstrated severe acute interstitial nephritis. The culprit medications were held and he was treated with steroids. With immunosuppression, creatinine improved to pretreatment values.

scholarly journals Management of Immune Checkpoint Inhibitor-Related Rheumatological Toxicities

2020 ◽  
Vol 20 (01) ◽  
pp. 25-34
Author(s):  
Pak Yui Fong ◽  
Shing Chuen Chow ◽  
Bernard Ming Hong Kwong ◽  
Charlene Cheuk Lam Lau ◽  
Christy Yik Ching Lau ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Eosinophilic Fasciitis ◽  
Low Grade ◽  
Programmed Death ◽  
Rheumatological Diseases ◽  
Cell Death Protein

Immune checkpoint inhibitors (ICIs) have forged a new direction for the treatment of cancer. However, ICIs – programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors – are also known to cause immune-related adverse events (irAEs). Rheumatological adverse events are uncommon and often low grade, but flares of underlying rheumatological diseases may be triggered. Guidelines are available for the effective management of the rheumatological adverse events that more frequently arise from the use of ICIs, such as inflammatory arthritis, inflammatory myopathies, Sjogren syndrome, scleroderma, and polymyalgia rheumatica and eosinophilic fasciitis.

scholarly journals Membranoproliferative Glomerulonephritis Associated with Nivolumab Therapy

2020 ◽  
Vol 2020 ◽  
pp. 1-4
Author(s):  
Jessica Cruz-Whitley ◽  
Nolan Giehl ◽  
Kuang-Yu Jen ◽  
Brian Young
Keyword(s):  
Immune Checkpoint ◽  
Membranoproliferative Glomerulonephritis ◽  
Immune Checkpoint Inhibitor ◽  
Tubulointerstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Anal Carcinoma ◽  
Kidney Injury ◽  
Unique Case ◽  
Programmed Death ◽  
Programmed Death 1

Nivolumab is an immune checkpoint inhibitor that targets programmed death-1 on T cells and is designed to amplify an immunologic reaction against cancer cells. However, upregulation of the immune system with checkpoint inhibition is nonspecific, and it can be associated with certain renal side effects, the best documented of which is acute tubulointerstitial nephritis. We present a unique case of a patient with acute kidney injury associated with nephrotic syndrome shortly after starting nivolumab therapy for metastatic anal carcinoma. Subsequent renal biopsy revealed membranoproliferative glomerulonephritis (MPGN). We believe this represents the first reported direct case of nivolumab-associated MPGN. As immunotherapy becomes more widely used in cancer treatment, particular attention must be paid to possible consequences of immune checkpoint inhibitors.

scholarly journals Nivolumab-induced hypothyoidism with consequent hypothyroid related myopathy

2019 ◽  
Vol 26 (1) ◽  
pp. 224-227 ◽  
Author(s):  
Eric D Johnson ◽  
Katie Kerrigan ◽  
Katerina Butler ◽  
Shiven B Patel
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Hormone Replacement ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Anti Tumor Activity

Purpose Nivolumab is a fully human IgG4 programmed death 1 immune checkpoint inhibitor (ICI) antibody that has anti-tumor activity by selectively blocking the interaction of the programmed death 1 receptor with its two known programmed death ligands PD-L1 and PD-L2. In doing so, this immune checkpoint inhibitor removes the negative signal stifling T cell activation and proliferation within the tumor microenvironment and demonstrates favorable antitumor activity. Case report We report an interesting case of immune checkpoint inhibitor-induced primary hypothyroidism with associated hypothyroid myopathy in a young patient with surgically resected stage IIIB melanoma receiving adjuvant nivolumab. He presented 12 weeks into therapy with severe myalgias, arthralgias, and intermittent disequilibrium of unclear etiology. Laboratory evaluation demonstrated a significant elevation in thyroid stimulating hormone and creatine kinase with an undetectable free T4 with standard laboratory measurement. With thyroid hormone replacement therapy alone, he had rapid improvement in his musculoskeletal symptoms and laboratory parameters over a three-week period. Discussion This case emphasizes the serious nature of endocrine immune-related adverse events in patients receiving immune checkpoint inhibitors. Additionally, it highlights that unlike most other immune-related adverse events, endocrine immune-related adverse events can generally be managed with adequate hormone replacement alone with swift improvements in symptoms. This allows patients to continue immune checkpoint inhibitors safely without immunosuppression which may dampen the anti-tumor activity of these agents. Conclusion This case highlights the importance of early recognition and the appropriate management of endocrine immune-related adverse events to maximize patient safety and good outcomes.

Tubulitis in a patient treated with nivolumab: Case report and literature review

2018 ◽  
Vol 2 (2-3) ◽  
pp. 107-112
Author(s):  
Viral Vakil ◽  
Mark Birkenbach ◽  
Katti Woerner ◽  
Lihong Bu
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint Inhibitors ◽  
Kidney Biopsy ◽  
Tubulointerstitial Nephritis ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Programmed Death Ligand 1 ◽  
Programmed Death ◽  
Metastatic Urothelial Carcinoma ◽  
Programmed Death 1

Kidney injury associated with use of immune checkpoint inhibitors that target the programmed death-1 molecule commonly manifests as acute tubulointerstitial nephritis on kidney biopsy. We present a case of a 66-year-old man who developed acute kidney injury at 6 months after initiation of treatment with anti-programmed death-1 antibody, nivolumab, for treatment of metastatic urothelial carcinoma. A renal biopsy showed focal moderate-to-severe lymphocytic tubulitis with minimal interstitial inflammation. Programmed death ligand-1 immunopositivity was detected only in tubules exhibiting lymphocytic tubulitis. The patient’s renal function improved to baseline with conservative management consisting of discontinuation of nivolumab followed by prednisone treatment.

scholarly journals Immune Checkpoint Inhibitor Therapy in Patients With Preexisting Inflammatory Bowel Disease

2020 ◽  
Vol 38 (6) ◽  
pp. 576-583 ◽  
Author(s):  
Hamzah Abu-Sbeih ◽  
David M. Faleck ◽  
Biagio Ricciuti ◽  
Robin B. Mendelsohn ◽  
Abdul R. Naqash ◽  
...  
Keyword(s):  
Adverse Events ◽  
T Lymphocyte ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Inhibitor Therapy ◽  
Checkpoint Inhibitor Therapy ◽  
Inflammatory Bowel

PURPOSE The risk of immune checkpoint inhibitor therapy–related GI adverse events in patients with cancer and inflammatory bowel disease (IBD) has not been well described. We characterized GI adverse events in patients with underlying IBD who received immune checkpoint inhibitors. PATIENTS AND METHODS We performed a multicenter, retrospective study of patients with documented IBD who received immune checkpoint inhibitor therapy between January 2010 and February 2019. Backward selection and multivariate logistic regression were conducted to assess risk of GI adverse events. RESULTS Of the 102 included patients, 17 received therapy targeting cytotoxic T-lymphocyte antigen-4, and 85 received monotherapy targeting programmed cell death 1 or its ligand. Half of the patients had Crohn’s disease, and half had ulcerative colitis. The median time from last active IBD episode to immunotherapy initiation was 5 years (interquartile range, 3-12 years). Forty-three patients were not receiving treatment of IBD. GI adverse events occurred in 42 patients (41%) after a median of 62 days (interquartile range, 33-123 days), a rate higher than that among similar patients without underlying IBD who were treated at centers participating in the study (11%; P < .001). GI events among patients with IBD included grade 3 or 4 diarrhea in 21 patients (21%). Four patients experienced colonic perforation, 2 of whom required surgery. No GI adverse event–related deaths were recorded. Anti–cytotoxic T-lymphocyte antigen-4 therapy was associated with increased risk of GI adverse events on univariable but not multivariable analysis (odds ratio, 3.19; 95% CI, 1.8 to 9.48; P = .037; and odds ratio, 4.72; 95% CI, 0.95 to 23.53; P = .058, respectively). CONCLUSION Preexisting IBD increases the risk of severe GI adverse events in patients treated with immune checkpoint inhibitors.

scholarly journals A case report of psoriasis flare following immunotherapy: Report of an important entity and literature review

2020 ◽  
Vol 8 ◽  
pp. 2050313X1989770 ◽  
Author(s):  
Anastasia Politi ◽  
Dimas Angelos ◽  
Davide Mauri ◽  
George Zarkavelis ◽  
George Pentheroudakis
Keyword(s):  
Adverse Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Skin Lesions ◽  
Inflammatory Disorder ◽  
Immune Mediated ◽  
Programmed Death ◽  
History Of ◽  
Programmed Death 1 ◽  
Cessation Of Treatment

Immune checkpoint inhibitors, such as anti-cytotoxic T-lymphocyte–associated antigen-4 and anti-programmed death-1, are a type of cancer immunotherapy approved for late-stage malignancy treatment. However, such therapies often induce immune-related adverse events. During anti-programmed death-1 blockade therapy, the most commonly reported adverse effects are skin toxicities, such as psoriasis—a chronic immune-mediated inflammatory disorder affecting the skin. We present the clinical characteristics of flared psoriasis in one patient under anti-programmed death-1 therapy who was diagnosed with T2N2M0/IIIB squamous lung carcinoma with a history of psoriasis for the past 5 years, exacerbated after the first cycle of nivolumab. After the third cycle, the extensive skin plaques necessitated treatment cessation. Following the discontinuation of anti-programmed death-1 treatment, skin lesions were treated locally. Possibly, anti-programmed death-1 immunotherapy can trigger immune-mediated diseases, such as psoriasis. Physicians should be alert to immune-related adverse events. Continuation or permanent cessation of treatment depends on the severity and reversibility of immune-related adverse events.

scholarly journals Kidney injury associated with antitumor therapy: focus on the adverse events of modern immuno-oncological drugs

2021 ◽  
Vol 93 (6) ◽  
pp. 649-660
Author(s):  
Elena S. Kamyshova ◽  
Irina N. Bobkova ◽  
Marina I. Sekacheva
Keyword(s):  
Adverse Events ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Inhibitory Effect ◽  
Immune System Activation ◽  
Programmed Death ◽  
Programmed Death Protein 1 ◽  
System Activation ◽  
New Generation

Immune checkpoint inhibitors (ICIs), including cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) and programmed death protein 1 (PD-1) or its ligand (PD-L1), are a new generation of immuno-oncological drugs that to date have demonstrated efficacy in a number of malignancies. The mechanism of ICT inhibitors action consist in the potentiation of the immune response by eliminating the tumor cells inhibitory effect on the T-lymphocytes activation. However, excessive immune system activation can cause the development of a special class of immune-related adverse events (irAEs) involved a wide variety of organs and systems, including the kidneys. Despite the fact that immuno-mediated kidney injury caused by ICI therapy develops quite rarely, it can be serious and determine the patient's prognosis, which necessitates early diagnosis and timely start of treatment. In this regard, awareness of the manifestations of ICI-associated renal irAEs is particularly relevant not only for oncologists and for nephrologists, but for doctors of other specialties. In this review, we elucidated the main variants of immuno-mediated kidney injury caused by ICI therapy, discussed possible predictors and mechanisms of their development, and considers the general principles of diagnosis and management of patients according to the severity of irAEs.

scholarly journals A new expression of immune checkpoint inhibitors’ renal toxicity: when distal tubular acidosis precedes creatinine elevation

2019 ◽  
Vol 13 (1) ◽  
pp. 42-45
Author(s):  
Xavier Charmetant ◽  
Cécile Teuma ◽  
Jennifer Lake ◽  
Frédérique Dijoud ◽  
Vincent Frochot ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Renal Toxicity ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Acute Interstitial Nephritis ◽  
Tubular Dysfunction ◽  
Distal Tubular Acidosis

Abstract The main manifestation of acute interstitial nephritis (AIN) due to immune checkpoint inhibitors is acute kidney injury. We report here a biopsy-proven AIN revealed by tubular acidosis. This case highlights that immune checkpoint inhibitor prescribers must be aware of electrolytic disorders since tubular dysfunction can precede serum creatinine increase and reveal renal toxicity.

Multiple autoimmune side effects of immune checkpoint inhibitors in a patient with metastatic melanoma receiving pembrolizumab

2020 ◽  
pp. 107815522092154
Author(s):  
Nikhila Kethireddy ◽  
Steffi Thomas ◽  
Poorva Bindal ◽  
Prateek Shukla ◽  
Upendra Hegde
Keyword(s):  
Type 1 Diabetes ◽  
Adverse Events ◽  
Immune Checkpoint ◽  
Polymyalgia Rheumatica ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Close Monitoring ◽  
Programmed Death ◽  
Programmed Death 1

Introduction Immune agents including anti-programmed death receptor-1 and anti-cytotoxic T-lymphocyte antigen-4 have been associated with numerous immune-related complications. Pembrolizumab, a programmed death-1 inhibitor, has been associated with a number of immune-related adverse events such as pneumonitis, colitis, hepatitis, hypophysitis, hyperthyroidism, hypothyroidism, nephritis, and type 1 diabetes. Case report We present a rare case of an elderly male on pembrolizumab who suffered from four autoimmune toxicities including type 1 diabetes, pneumonitis, hypothyroidism, and polymyalgia rheumatica likely catalyzed by age-related immune activation. Management and outcome: Immunotherapy was indefinitely stopped, and patient was started on steroids for the immune-related adverse events with complete resolution of polymyalgia rheumatica. Thyroid dysfunction resolved once he started thyroid replacement therapy. His diabetes is well controlled with insulin and is followed by endocrinology. He continues on prednisone for immune-mediated pneumonitis with a good response with regular monitoring via computed tomography scans and pulmonary consultation. Discussion Few cases wherein multiple toxicities are seen within one patient are reported. Aging appears to be a risk factor for immune-related adverse events. Aging is associated with an increased incidence of autoimmunity as programmed death-1 ligand expression represents an important mechanism that tissues use to protect from self-reactive effector T cells. Programmed death-1 blockade breaks this protective mechanism and enhances autoimmune diseases. Therefore, close monitoring and extreme vigilance is warranted while using immune checkpoint inhibitors including pembrolizumab as multiple toxicities can occur within a short span of infusion, especially in elderly individuals. Prompt discontinuation and the use of a multidisciplinary team are prudent to prevent further morbidity and mortality.

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