Possible atezolizumab-associated acute kidney injury and immune thrombocytopenia

2020 ◽  
Vol 26 (7) ◽  
pp. 1791-1794 ◽  
Author(s):  
Ali Yılmaz ◽  
Cem Mirili ◽  
Mehmet Bilici ◽  
Salim Başol Tekin
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Drug Induced ◽  
Musculoskeletal Problems ◽  
Third Line ◽  
Anti Tumor Activity

Introduction The immune checkpoint inhibitors (ICIs), which are used to activate the immune system and stimulate anti-tumor activity, are preferred in many cancers. Atezolizumab acts by blocking programmed cell death ligand (PD-L1) and may cause immune hyperstimulation in healthy tissues like other ICIs, resulting in immune-related adverse events (irAEs). Hepatitis, colitis, pneumonitis, hypophysitis, hypothyroidism, rash, musculoskeletal problems are the most common irAEs, and on the other hand, acute kidney injury (AKI) and immune thrombocytopenic purpura (ITP) are infrequent. Case report We present a case with non-small cell lung cancer (NSCLC) treated with atezolizumab 1200 mg every three weeks for third-line treatment. The patient was admitted with fatigue and back pain. The patient’s complaints started one week after the first dose of atezolizumab. The patient had renal injury and thrombocytopenia and was diagnosed with drug-induced AKI and ITP. Management and outcome After platelet replacement, intravenous immunoglobulin (IVIG), and steroid therapy, the patient whose platelet count was normalized and creatinine level regressed was discharged, and routine follow-up continues. Discussion Here, we present a case with NSCLC treated with atezolizumab and with drug-induced ITP and AKI association. Given that atezolizumab and other immune checkpoint inhibitors are being utilized in the treatment of cancers, physicians should be aware of the irAEs, including the AKI and ITP.

scholarly journals Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors

2016 ◽  
Vol 90 (3) ◽  
pp. 638-647 ◽  
Author(s):  
Frank B. Cortazar ◽  
Kristen A. Marrone ◽  
Megan L. Troxell ◽  
Kenneth M. Ralto ◽  
Melanie P. Hoenig ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Clinicopathological Features

MO404ACUTE KIDNEY INJURY DUE TO IMMUNE CHECKPOINT INHIBITORS (CPIS) NEPHROTOXICITY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Fausta Catapano ◽  
Elisa Persici ◽  
Giulia Ubaldi ◽  
Francesca Romani ◽  
Elena Mancini
Keyword(s):  
Acute Kidney Injury ◽  
Renal Function ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Renal Outcome ◽  
Long Term Follow Up

Abstract Background and Aims The approved therapeutic indication for immune checkpoint inhibitors (CPIs) are rapidly expanding; however the immune-related toxicities associated with CPIs can limit its efficacy. Case Report. A 52 year-old female diagnosed with left ocular melanoma and treated for 14 months with nivolumab developed non-oliguric, stage 3 (KDIGO), Acute Kidney Injury (AKI) and mixed proteinuria (0.6 g/day), then was transferred in our Unit. As known causes of AKI were excluded, kidney biopsy was performed. By Optical Microscopy, there were 33 normal glomeruli; arteries and arterioles were normal. The main damage was interstitial and characterized by tubulitis, tubular necrosis, non-isometric citoplasmatic vacuolization and diffuse, acute and chronic, CD4+, inflammatory infiltrate (Figure 1, 2). By Immunofluorescence, 27 glomeruli were negative for all eight tested antibodies (IgA, IgM, IgG, F, C3, C1q, kappa and lambda light chains). On the basis of these histological findings, Nivolumab-induced Acute Tubulo-Interstitial Nephritis was diagnosed. Nivolumab was discontinuated. Patient was treated by steroids and she achieved almost complete renal function recovery (Figure 3). Conclusions. CPIs can induce a long-term Acute Kidney Injury. Histological features are characterized by Acute Tubulo-Interstitial Nephritis. Steroids can improve renal outcome. In patients treated with CPIs a multidisciplinary management between oncologists and nephrologists is desirable for monitoring renal function at basal, after drug administration and in the long-term follow-up.

scholarly journals Acute Kidney Injury after Pembrolizumab-Induced Adrenalitis and Adrenal Insufficiency

2018 ◽  
Vol 8 (2) ◽  
pp. 171-177 ◽  
Author(s):  
Ramy M. Hanna ◽  
Umut Selamet ◽  
Patrick Bui ◽  
Shih-Fan Sun ◽  
Olivia Shenouda ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Adrenal Insufficiency ◽  
Interstitial Nephritis ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Clinical Course ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Glomerular Disease ◽  
Severe Hypotension

Pembrolizumab is an immune checkpoint inhibitor that targets the programmed cell death protein 1 (PD-1) antigen and induces an immune response against tumor tissues. It has been successful in inducing remission in patients with severe metastatic disease, often refractory to other chemotherapeutic agents. The risk of injury of other organ systems has been noted with reported cases of glomerular disease and endocrine disease. In addition, hypophysitis as well as dermatological and gastroenterological side effects have been reported. Renal injury with immune checkpoint inhibitors like nivolumab and pembrolizumab is usually mediated via interstitial nephritis, though glomerular disease presentations like anti-neutrophil cytoplasmic antibody-associated vasculitis, immune complex disease, and thrombotic microangiopathy have also been reported. We report a 70-year-old Caucasian male who underwent treatment with pembrolizumab for adenocarcinoma of the lung. He developed acute adrenal insufficiency and concomitant severe hypotension upon presentation. He did not require renal replacement therapy, rather his severe acute kidney injury resolved with hydration, normalization of blood pressures with vasopressors, and treatment with high-dose corticosteroids. His urinary indices (fractional excretion of urea, FEUrea) and clinical course were highly suspicious for acute tubular necrosis that resolved quickly after treating his underlying adrenalitis. The urinary sediment, proteinuria, and clinical course were not typical for the usually expected renal lesion of interstitial nephritis in patients treated with immune checkpoint inhibitors.

640 Characterizing severe acute kidney injury in patients treated with immune checkpoint inhibitors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A676-A676
Author(s):  
Chung-Jiah Chen ◽  
Lisa Kim ◽  
Ashley Weaver ◽  
Sandip Patel
Keyword(s):  
Acute Kidney Injury ◽  
Renal Biopsy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
University Of California ◽  
High Dose ◽  
Renal Ultrasound ◽  
The University

BackgroundRenal immune-related adverse events (irAEs), are relatively rare in patients treated with immune checkpoint inhibitors (ICIs). This retrospective analysis characterizes the etiology of severe acute kidney injury (AKI) in patients treated with ICIs at the University of California, San Diego.MethodsThe electronic medical record was used to identify all patients with an estimated glomerular filtration rate (eGFR) <15 mL/hr who received ipilimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, avelumab, cemiplimab between 1/2000 and 1/2019. Patients with baseline eGFR < 15 mL/hr or who experienced an eGFR decline to <15 mL/hr prior to ICI initiation were excluded. Extracted data included serum creatinine, eGFR, ICI dose, urinalysis, renal ultrasound, clinical documentation of both ICI-related nephritis and other suspected causes of AKI. These data were analyzed to determine cause of AKI and possible relation to ICI.Results46 patients who received ICI therapy and subsequently developed an AKI with eGFR <15 mL/hr were identified. Three of these 46 patients (6.5%) had AKIs partially or predominately attributed by the clinician to ICI therapy (table 1). Characteristics of ICI-related AKI for these patients are summarized in (table 2). AKI onset occurred 32–110 days after ICI initiation. All three patients exhibited proteinuria, pyuria, and hematuria on urinalysis with negative urine cultures, but none underwent confirmatory renal biopsy. Only one patient had urine eosinophils checked, which was negative. Two (66%) of these patients received high-dose corticosteroids with subsequent complete eGFR recovery. Neither of these two patients required renal replacement therapy. One patient (33%) declined corticosteroid treatment due to concomitant multiorgan failure. An additional four (8.7%) patients developed multifactorial AKIs with other concurrent IRAEs that were treated with corticosteroids, but were not formally diagnosed with ICI-related AKI.Abstract 640 Table 1AKI etiologies in ICI-treated patientsAbstract 640 Table 2Patient characteristics in ICI-related AKIConclusionsIn our cohort, 6.5% of patients who develop AKI after receiving ICI therapy experienced immune-related nephritis. A further 8.7% of patients experienced other irAEs with AKI, suggesting that the true prevalence of immune-related nephritis is likely underdiagnosed. Notably, 84.8% of patients who develop AKI after ICI therapy have a non-ICI-related etiology, and no patient in our cohort of 46 patients underwent renal biopsy, highlighting the need for blood-based biomarker development for immune-related nephritis.Ethics ApprovalThe study was approved by the University of California San Diego’s Institutional Review Board, approval number 150348.

scholarly journals 363 Vactosertib and durvalumab as second or later line treatment for PD-L1 positive non-small cell lung cancer: interim result

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A388-A388
Author(s):  
Byoung Chul Cho ◽  
Ki Hyeong Lee ◽  
Ji-Youn Han ◽  
Byoung Yong Shim ◽  
Hye Ryun Kim ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Objective Response Rate ◽  
Immune Checkpoint Inhibitors ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Platinum Based Chemotherapy ◽  
Number Of Patients ◽  
Anti Tumor Activity

BackgroundTargeting transforming growth factor-β (TGF-β) is reported to augment the efficacy of immune checkpoint inhibitors (ICIs) through either enhanced anti-tumor immunity or the correction of tumor microenvironment (TME). Therefore, the combination of vactosertib, a highly selective TGF-β RI kinase inhibitor, and durvalumab is anticipated to improve anti-tumor activity of the ICI. A phase 1b/2a study was conducted to evaluate the combination of vactosertib and durvalumab in patients with advanced NSCLC who progressed after platinum-based chemotherapy.MethodsPatients were treated with vactosertib at a dose of 200 mg twice daily (five days on and two days off) and durvalumab at a dose of 1500 mg every four weeks. Eligible patients were ≥19 years old with good performance status (ECOG 0–1) and have no prior exposure to immune checkpoint inhibitors or other TGF- β R1 kinase inhibitors. The objectives of this analysis were to evaluate the safety, antitumor activity including objective response rate (ORR), duration of response (DOR), and time to response (TTR) as well as circulating pharmacodynamic biomarkers related to TGF-β signaling. Response was assessed per RECIST (v1.1).ResultsBy August 4 2020, twenty-six PD-L1 positive (SP263 assay) patients were analyzed. Median age was 61.5 years (range 48–83), 69.2% were male, median number of previous lines of chemotherapy was 1 (range 1–4), and all patients were PD-L1 positive (15 patients with PD-L1≥25% and 11 patients with PD-L1 1–24%). The most frequently reported treatment-related adverse events (TRAE) were itching (38.5%) and skin rash (34.6%), but no Gr≥3 itching and rash were observed. Each case of the following was reported as Grade 3 TRAEs: adrenal insufficiency, anemia, and pneumonitis; Grade 4 TRAE, CPK increase, was observed in one patient. Objective response rate was 30.8% and 40.0% in patients with PD-L1≥1% and ≥25% respectively. Circulating PAI-1 and CTGF evaluated in 15 patients decreased significantly on Cycle 1 day 5. Ongoing biomarker results will be presented.ConclusionsThe combination of vactosertib and durvalumab has demonstrated a manageable safety profile and encouraging anti-tumor activity as a potential therapeutic strategy in patients with advanced NSCLC. The efficacy outcomes of this combination in a larger number of patients with advanced NSCLC will be followed.Trial RegistrationNCT03732274Ethics ApprovalThe study was approved by Ethics Board of Severance Hospital (4-2018-0892), National Cancer Center (NCC2019-0057), St. Vincent’s Hospital (VC19MDDF0205), and Chungbuk National University Hospital (2019-08-015).

Tailored immunotherapy approach with nivolumab in advanced transitional cell carcinoma (TITAN-TCC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 446-446
Author(s):  
Marc-Oliver Grimm ◽  
Bernd Schmitz-Dräger ◽  
Uwe Zimmermann ◽  
Barbara Grün ◽  
Gustavo Bruno Baretton ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Transitional Cell ◽  
Added Value ◽  
Phase Iii ◽  
First Line ◽  
Third Line

446 Background: Several PD-1 immune-checkpoint inhibitors including Nivolumab (Nivo) are approved in urothelial cancer. Recently, in the front line setting, improved activity of combined PD-L1 and CTLA4 immune-checkpoint inhibition has been reported and a phase III trial with Nivolumab + Ipilimumab (Nivo+Ipi) is ongoing. Here we report a response-based tailored approach starting treatment with Nivo monotherapy using Nivo+Ipi as immunotherapeutic “boost”. Methods: Between July 2017 and April 2019 86 patients were enrolled and treated according to protocol version 3 (cohort 1). Patients started with Nivo 240 mg Q2W induction. After 4 dosings and tumor assessment at week 8 (i) responders (PR/CR) to Nivo monotherapy continued with maintenance while (ii) patients with stable (SD) or progressive disease (PD) received 2 cycles Nivo3+Ipi1 followed by another 2 cycles Nivo1+Ipi3 if not responding. Median follow-up is 8.7 months. The primary endpoint is confirmed investigator-assessed objective response rate (ORR) per RECIST1.1. Secondary endpoints include activity of Nivo monotherapy at week 8, remission rate with Nivo+Ipi “boosts”, safety, overall survival and quality of life. Results: Of the patients 42, 39 and 5 were first, second and third line, respectively. Median age was 67 years (range 45-84), 61 patients (71 %) were male and 25 female. ORR with Nivo monotherapy at first assessment (week 8) was 29 % and 23 % in first and second/third line, respectively. Of the patients 41 received Nivo+Ipi “boosts” after week 8 while 12 received later “boosts”. Best overall response (BOR) rate with Nivo induction ± Nivo+Ipi “boosts” was 48 % and 27 % in first and second/third line, respectively. In first line 7/17 (41 %) patients receiving Nivo+Ipi after week 8 had an improved response compared to 2/24 (8.3 %) in second/third line. Of the patients who continued with Nivo maintenance after week 8 and received later “boosts” 2/12 (17 %) had a PR and 2/12 (17 %) improved to SD. Treatment-related AEs will be presented. Conclusions: TITAN–TCC explores a response-driven use of Nivo+Ipi as an immunotherapeutic “boost”. In first line, this significantly improved ORR compared to the expected response rate of Nivo monotherapy, providing further evidence to the added value of Ipi in combination with Nivo. Further follow-up is ongoing to characterize duration and depth of response. Clinical trial information: NCT03219775 . Research Sponsor: Bristol-Myers Squibb[Table: see text]

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