scholarly journals IgA Nephropathy Secondary to Ipilimumab Use

2021 ◽  
pp. 327-333
Author(s):  
Sean C. Dougherty ◽  
Nisa Desai ◽  
Helen P. Cathro ◽  
Amanda Renaghan
Keyword(s):  
Iga Nephropathy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Human Monoclonal Antibody ◽  
Kidney Injury ◽  
Stage Iv ◽  
Clinical History ◽  
High Prevalence ◽  
Initiation Of Therapy ◽  
Nephrotic Range Proteinuria

Ipilimumab is a human monoclonal antibody targeting cytotoxic T-lymphocyte-associated protein 4 approved for the treatment of non-small-cell lung cancer (NSCLC) and other malignancies. Despite a high prevalence of other immune-related adverse events (irAEs), checkpoint inhibitor (CPI)-related nephrotoxicity has been reported less frequently. In this clinical case report, we describe the evaluation of a 70-year-old female with stage IV NSCLC who presented with nephrotic range proteinuria 4 weeks after receiving her first cycle of ipilimumab. She underwent a renal biopsy and was found to have IgA nephropathy that was presumed to be secondary to ipilimumab use, given recent initiation of therapy and clinical history. Unfortunately, despite prompt initiation of corticosteroids, her acute kidney injury progressed and she required hemodialysis, later transitioning to hospice. To our knowledge, this is one of few reported cases of IgA nephropathy secondary to CPI use. With increasing use of CPIs, this case further emphasizes the need for continued surveillance for irAEs, which can occur at any point in a patient’s treatment course.

The efficacy and safety of ipilimumab (MDX-010) in patients with unresectable stage III or stage IV malignant melanoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8523-8523 ◽  
Author(s):  
J. S. Weber ◽  
E. M. Hersh ◽  
M. Yellin ◽  
G. M. Nichol ◽  
W. Urba ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Late Onset ◽  
Human Monoclonal Antibody ◽  
Stage Iv ◽  
Efficacy And Safety ◽  
Unresectable Stage ◽  
Biologic Effects ◽  
Study Completion

8523 Background: Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), enhances antitumor immune responses resulting in durable objective responses. In this study we examined the efficacy and safety of different ipilimumab preparations and regimens in patients with unresectable metastatic melanoma. Methods: In this study (MDX010–15), 34 patients received either 2.8 or 5 mg/kg transfectoma- or 3 mg/kg hybridoma-derived ipilimumab on days 1, 57 and 85. Additionally, 30 patients received single doses of 7.5 (6 pts), 10 (7 pts), 15 (6 pts) or 20 mg/kg (11 pts) transfectoma-derived ipilimumab. Once single doses up to 20 mg/kg were found to be well tolerated, 24 additional patients were given up to 4 doses of 10 mg/kg ipilimumab on days 1, 22, 43 and 64. Complete or partial responses (CR, PR), stable disease (SD) and adverse events (AEs) were monitored. Results: 1 CR, 3 PRs and 10 durable SDs were confirmed in 88 treated patients at the time of analysis. ORs were durable (∼29+, 34, 38+ and 39+ weeks [w]) and ongoing in 3 patients at study completion. PR in 1 patient was observed after ∼18.5w and developed to an ongoing CR at ∼51w. In another, SD for ∼16w preceded a ∼30w+ PR. Durable SD ranged from ∼21 to 79+w and is ongoing in 4 patients. Patients with OR or SD had immune-related AEs including rash, pruritis (G1/2), diarrhea (G1/2/3) or colitis (G2). AEs were severe in 27 patients, and considered ipilimumab-related (mostly G3/G4 colitis and diarrhea) in 9 (10% of all treated patients). Conclusions: Preliminary results suggest ipilimumab is generally safe and well tolerated. Late-onset ORs can occur, sometimes preceded by months of SD. ORs and SDs tend to be durable. Drug-related AEs of an immune nature are probably related to the biologic effects of ipilimumab, and are similar to those reported previously. No obvious dose relationship to AEs has been seen to date. [Table: see text]

Checkpoint Inhibitor Colitis Masked by Multi-drug Effect

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S52-S52
Author(s):  
J W Davis ◽  
M Canevari ◽  
J C Shaw
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Drug Effect ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Bowel Perforation ◽  
Clinical History ◽  
Tissue Reaction ◽  
Accurate Diagnosis ◽  
Architectural Distortion ◽  
Infectious Colitis

Abstract Casestudy: The utilization of checkpoint inhibitors such as programmed cell death protein 1 (PD-1/PD-L1) inhibitors (nivolumab) and cytotoxic T-lymphocyte antigen 4 inhibitors (ipilimumab) for treatment of certain malignancies has steadily gained popularity. Medication related colitis is uncommon, with a reported incidence of 1–9% depending on the checkpoint inhibitor used, and the histologic features have been characterized in recent literature. Because of the immunomodulating effect of these drugs, infectious colitis is in the differential diagnosis of enteritis. Multi-drug therapy in many of these patients further complicates identification of the culprit drug. We present the case of a 63-year-old male with metastatic renal cell carcinoma being treated with both nivolumab and ipilimumab who presented with acute on chronic non-bloody diarrhea. His clinical course was complicated by hypotension, acidosis and coagulopathy. The clinical differential for his colitis was cytomegalovirus infection versus a checkpoint inhibitor colitis. Colonoscopy revealed continuous circumferential loss of vascularity and diffuse erythema throughout the colon. Histology showed acute colitis with prominent apoptosis, cryptitis, crypt abscesses, and rare ringed mitotic figures, but without architectural distortion. Occasional smooth purple crystals consistent with pill material were present in the mucosa, but without significant tissue reaction. No pathogenic organisms were identified, and a cytomegalovirus immunostain was negative. These histologic findings in concert with the clinical history are consistent with checkpoint inhibitor colitis and multi-drug effect. A review of the patient’s chart showed cholestyramine was added to the patient’s regimen during hospitalization, which was consistent with the morphologic appearance of the crystals. Given the acute complications of checkpoint inhibitor induced enterocolitis and potential for increased morbidity (rare cases of bowel perforation and subsequent resection), accurate diagnosis is imperative. Management of checkpoint inhibitor associated colitis ranges from initiation of immunosuppression to checkpoint inhibitor cessation. When these findings are masked by multi-drug effect, accurate diagnosis can be difficult.

Ipilimumab-induced hypophysitis in melanoma patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8568-8568 ◽  
Author(s):  
Typhanie Carré ◽  
Caroline Gaudy-Marqueste ◽  
Frédérique Albarel ◽  
Sandrine Monestier ◽  
Stéphanie Mallet ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Clinical Symptoms ◽  
Cytotoxic T Lymphocyte ◽  
Human Monoclonal Antibody ◽  
Stage Iv ◽  
Adjuvant Setting ◽  
The Third ◽  
Melanoma Patients ◽  
Mri Changes ◽  
To Receive

8568 Background: Ipilimumab (Ipi) is a human monoclonal antibody directed against cytotoxic T-lymphocyte antigene-4 (CTLA-4) recently approved for the treatment of metastatic melanoma (MM) and currently under investigation in the adjuvant setting. Methods: Retrospective analysis of patients treated with ipi between June 2006 and September 2011 in our department in Marseille. As some patients are still blinded in trials, the exact number of patient under ipi is unknown. We present a minimal percentage (>%) assuming that the 120 patients received ipi. Results: A total of 120 patients were treated: 76 stages IV MM, from which 16 in the BMS clinical trials (CA184-022, -024, and-025 and MDX 010-20) and 44 stages III MM (in the BMS CA184-029 trial). Stage IV MM were administered 0.3, 3 or 10mg/kg IV dosage, while stages III MM were randomly assigned to receive 10 mg/ kg or placebo (1:1 ratio). Hypophysitis was diagnosed in 12 patients (>10%): 2/76 patients with stage IV MM (>2. 6 %) and 10/44 patients with stage III MM (>22.7). Diagnosis was performed at the 1st, 3rd and 4th administration in respectively 2 (1.6%), 6 (50%) and 4 patients (33.3%). Clinical symptoms included headaches (n=11; 91.6%), asthenia (n=7; 58.3%) and decreased libido (n=2; 1.6%). Adrenal, thyroidal and gonadal axis were affected in respectively 6 (50%), 9 (75%) and 7 patients (58.3%). MRI changes were observed in 7 patients (58.3%): pituitary swelling in 5 patients (41.6%) and heterogeneous enhancement in 4 patients (33.3%) including 2 patients with normal biology. Corticosteroids supplementation was required in 11 patients and thyroidian supplementation in 4 patients. Clinical symptoms regressed within one week in 8 patients (66.6%). Conclusions: Ipi-induced hypophysitis is detectable only if clinicians are aware of these unspecific signs. Only MRI can make diagnosis in some patients without clinical and/or biological signs. Our data suggest that it develops especially for 10mg/kg dosage, after the third administration, and that the rate could be higher in patients with a normal immune system (adjuvant treatment), than in metastatic ones. Hormonal supplementation usually controls the disease.

Checkpoint Inhibitor-Induced Colitis: A Case Series

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S63-S64
Author(s):  
S R Avalos Hernandez ◽  
S A Anderson ◽  
V Dal Zotto
Keyword(s):  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Wide Spectrum ◽  
Case Series ◽  
Clinical History ◽  
Symptom Improvement ◽  
Pathologic Features ◽  
Active Colitis ◽  
Histopathologic Features

Abstract Introduction/Objective Checkpoint inhibitors are novel immune-stimulating antibodies that have revolutionized the management and prognosis of several malignancies. The primary targets are cytotoxic T-lymphocyte–associated antigen-4 (anti-CTLA-4; e.g. pembrolizumab) and programmed cell death-1 receptor (anti-PD-1; e.g. ipilimumab and nivolumab). In spite of the significant advantages, many immune-related adverse effects have been identified. One of which is checkpoint inhibitor-induced colitis (CIC). Although there is awareness of the histopathologic features of anti- CTLA-4 induced colitis, there is much to be discovered about the pathologic features of anti-PD-1 colitis. Methods We herein report three cases of CIC. There were two women and 1 male (age range, 50 to 73-years-old, mean 64-years-old) who presented with diarrhea and/or hematochezia after multiple cycles of pembrolizumab or ipilimumab/ nivolumab combination therapy. Endoscopic examination was abnormal in all of these cases. Results The histologic features were similar in two cases, with moderate active chronic colitis and one case with focal active colitis. Two of the three patient were given steroids in addition to their regular medications with symptom improvement. One patient was removed off all medications and enrolled into hospice due to disease progression. CIC has been an increasingly recognized immune-related adverse effect that has a wide spectrum of clinical presentations ranging from mild diarrhea and abdominal pain to severe colitis and intestinal perforation. However, it is thought to be underestimated. Histologically, CIC can mimic inflammatory bowel disease, microscopic colitis and active colitis. Our cases showed histopathologic features mimicking those of ulcerative colitis. Conclusion Awareness of CIC is crucial for the multidisciplinary management essential for these patients. The histopathologic pattern coupled with the clinical history can allow pathologists to confirm the diagnosis of CIC and facilitate timely diagnosis and treatment.

scholarly journals IgA vasculitis (Henoch-Schönlein purpura) nephritis and psoriasis in a child: is there a relationship?

2021 ◽  
Author(s):  
Ana Sofia Vaz ◽  
Raquel Penteado ◽  
Carolina Cordinhã ◽  
Carmen Carmo ◽  
Clara Gomes
Keyword(s):  
Iga Nephropathy ◽  
Systemic Vasculitis ◽  
Kidney Injury ◽  
Common Mechanism ◽  
Henoch Schonlein Purpura ◽  
Systemic Involvement ◽  
Kidney Involvement ◽  
Schonlein Purpura ◽  
Nephrotic Range Proteinuria ◽  
Henoch Schönlein Purpura

Abstract Background Psoriasis is a chronic immune-mediated disorder that primarily affects the skin in both adults and children but can also have systemic involvement, particularly with arthritis and kidney injury. IgA nephropathy is the most frequent kidney disorder associated with psoriasis. Approximately one third of all cases of psoriasis begin in childhood, but association between psoriasis and renal disorders has scarcely been reported in pediatric patients. Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized by IgA deposits in the vessel walls of affected organs and in the mesangium of the kidney. HSP nephritis histopathology is identical to IgA nephropathy. Case report A 6-year-old boy with recent onset of psoriasis developed HSP with kidney involvement, clinically manifested by nephrotic-range proteinuria and hematuria. Kidney biopsy revealed fibrocellular glomerular crescents and mesangial IgA deposits compatible with IgA nephropathy. Treatment with systemic corticosteroids led to the control of hematuria, but as nephrotic-range proteinuria persisted, cyclophosphamide was added, leading to a gradual decrease in proteinuria. Conclusions We propose an underlying common mechanism in the pathogenesis of both HSP and psoriasis, involving a dysregulation of the IgA-mediated immune response, which could predispose to both entities as well as to kidney damage and IgA nephropathy in these patients.

Immune Checkpoint Inhibitor (ICPI) induced Nephrotoxicity – An Insight.

JMS SKIMS ◽  
2020 ◽  
Vol 23 (3) ◽  
Author(s):  
Mohmad Hussian Mir ◽  
Tariq Ahmad Bhat ◽  
Khalid Parvez Sofi ◽  
Imtiyaz Ahmad Wani ◽  
Muzafar Maqsood Wani
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Kidney Injury ◽  
Check Point ◽  
Transplant Recipients ◽  
Kidney Transplant Recipients ◽  
New Class ◽  
Transplant Patients ◽  
Check Point Inhibitors

Immune check point inhibitors (ICPIs) are a new class of anti-neoplastic agents being increasingly used by oncologists to treat various malignancies. These drugs have been associated with varied side effects and have a nephrotoxic potential. Many cases of ICPI induced acute kidney injury are increasingly being reported. Their use in CKD patients on dialysis as well as in kidney transplant recipients is associated with various challenges. This review discusses the use of ICPIs in CKD, dialysis and renal transplant patients and their nephrotoxic potential  

scholarly journals Checkpoint inhibitor induced hepatitis and the relation with liver metastasis and outcome in advanced melanoma patients

2021 ◽  
Author(s):  
Maaike Biewenga ◽  
Monique K. van der Kooij ◽  
Michel W. J. M. Wouters ◽  
Maureen J. B. Aarts ◽  
Franchette W. P. J. van den Berkmortel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Liver Metastasis ◽  
Combination Therapy ◽  
Real World ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Negative Effect ◽  
Melanoma Patients

Abstract Background Checkpoint inhibitor-induced hepatitis is an immune-related adverse event of programmed cell death protein 1 (PD-1) inhibition, cytotoxic T-lymphocyte associated 4 (CTLA-4) inhibition or the combination of both. Aim of this study was to assess whether checkpoint inhibitor-induced hepatitis is related to liver metastasis and outcome in a real-world nationwide cohort. Methods Data from the prospective nationwide Dutch Melanoma Treatment Registry (DMTR) was used to analyze incidence, risk factors of checkpoint inhibitor-induced grade 3–4 hepatitis and outcome. Results 2561 advanced cutaneous melanoma patients received 3111 treatments with checkpoint inhibitors between May 2012 and January 2019. Severe hepatitis occurred in 30/1620 (1.8%) patients treated with PD-1 inhibitors, in 29/1105 (2.6%) patients treated with ipilimumab and in 80/386 (20.7%) patients treated with combination therapy. Patients with hepatitis had a similar prevalence of liver metastasis compared to patients without hepatitis (32% vs. 27%; p = 0.58 for PD-1 inhibitors; 42% vs. 29%; p = 0.16 for ipilimumab; 38% vs. 43%; p = 0.50 for combination therapy). There was no difference in median progression free and overall survival between patients with and without hepatitis (6.0 months vs. 5.4 months progression-free survival; p = 0.61; 17.0 vs. 16.2 months overall survival; p = 0.44). Conclusion Incidence of hepatitis in a real-world cohort is 1.8% for PD-1 inhibitor, 2.6% for ipilimumab and 20.7% for combination therapy. Checkpoint inhibitor-induced hepatitis had no relation with liver metastasis and had no negative effect on the outcome.

scholarly journals Decelerated tumor growth due to hypothyroidism with prolongation of survival in a patient with lung adenocarcinoma: a case report

2019 ◽  
Vol 48 (3) ◽  
pp. 030006051988530
Author(s):  
Jia Hou ◽  
Shan-Shan Xiong ◽  
Zhao-Qi Huang ◽  
Xing-Dong Cai
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitor ◽  
Tumor Therapy ◽  
Stage Iv ◽  
Small Cell Lung ◽  
Anti Cancer ◽  
Advanced Stages

Lung adenocarcinoma is a form of non-small-cell lung cancer with high mortality in the advanced stages, and is one of the most common histological subtypes of lung cancer in most countries. Prognosis of lung adenocarcinoma is generally poor, with a median survival of 4–13 months. We report a case of unusually prolonged survival of a patient with advanced lung adenocarcinoma complicated by hypothyroidism. A 71-year-old man with stage IV lung adenocarcinoma presented with hypothyroidism. Surprisingly, without any anti-tumor and anti-hypothyroidism therapy, he survived this lung cancer for longer than 2.5 years before his last follow-up visit. Patients with advanced lung adenocarcinoma rarely survive for longer than 2 years, even after therapy. We hypothesize that hypothyroidism is the cause for this discrepancy. Thyroid hormones can promote growth of carcinoma. Therefore, hypothyroidism appears to be beneficial to anti-cancer therapy. We believe that hypothyroidism, as an adverse event commonly occurring in anti-tumor therapy (e.g., an immune checkpoint inhibitor), might not be able to be completely eliminated.

scholarly journals Native kidney biopsies in Armenian and Swiss children: high prevalence of amyloidosis in Yerevan and of IgA nephropathy in Zurich

2014 ◽  
Vol 466 (1) ◽  
pp. 77-83
Author(s):  
Guido F. Laube ◽  
Ashot Sarkissian ◽  
Helen Nazaryan ◽  
Giuseppina Spartà ◽  
Armen Sanamyan ◽  
...  
Keyword(s):  
Iga Nephropathy ◽  
Native Kidney ◽  
High Prevalence

Liver Toxicity with Cancer Checkpoint Inhibitor Therapy

2018 ◽  
Vol 38 (04) ◽  
pp. 366-378 ◽  
Author(s):  
Brian Nadeau ◽  
Leslie Fecher ◽  
Scott Owens ◽  
Nataliya Razumilava
Keyword(s):  
Liver Toxicity ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Immunosuppressive Agents ◽  
Inhibitor Therapy ◽  
Significant Survival ◽  
The Us ◽  
Checkpoint Inhibitor Therapy ◽  
Clinically Significant

AbstractImmune checkpoint inhibition targeted against cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) and programmed cell death protein 1 (PD-1) has shown clinically significant survival benefit when used to treat multiple types of advanced cancer. These drugs have gained approval by the US Food and Drug Administration and their indications continue to increase. Checkpoint inhibitor therapy is associated with a unique side-effect profile characterized as immune-related adverse events (irAEs), which can result in significant morbidity and rarely mortality. Hepatotoxicity from checkpoint inhibitors is a less common irAE and often mild, while its incidence and severity vary based on the class and dose of checkpoint inhibitor, monotherapy versus combination therapy, and the type of cancer. Histological assessment of suspected irAEs is nonspecific and can show a variety of features. Hepatic irAEs can require discontinuation of checkpoint inhibitor therapy and treatment with immunosuppressive agents.

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