Case Report: A Case of Sintilimab-Induced Cystitis/Ureteritis and Review of Sintilimab-Related Adverse Events

Immune checkpoint inhibitors (ICIs) have been proven to be beneficial in multiple advanced malignancies. However, the widespread use of ICIs also occurred with various immune-related adverse events (irAEs). Here, we first report a case of sintilimab-related cystitis/ureteritis. A 53-year-old man with driver gene-negative pulmonary adenocarcinoma (cT1cN3M1c, Stage IVB) was being treated with sintilimab in combination of paclitaxel-albumin and bevacizumab as second-line treatment. He was hospitalized for haematuria, pollakiuria, painful micturition and low back pain after three courses. Urinalysis showed red blood cells (RBCs) and white blood cells (WBCs) were obviously increased, and serum creatinine (sCr) level was also significantly elevated. Urine culture and cytology were both negative, and cystoscopy revealed diffused redness of bladder mucosa. Urinary ultrasonography showed mild hydronephrosis and dilated ureter. The patient was diagnosed as immunotherapy-related cystitis/ureteritis after a multidisciplinary team (MDT) meeting. Once the diagnosis was made, corticosteroid therapy was given, which rapidly resolved the patient’s symptoms and signs. Computer tomography angiography (CTA) and CT urography (CTU) was conducted after sCr level was back to normal and demonstrated ureter dilation and hydroureter. Once symptoms relieved, bladder biopsy was performed and confirmed the bladder inflammation. The patient was subsequently switched to maintenance dose of methylprednisolone and tapered gradually. Since sintilimab has been used in advanced malignancies, we first reported a rare case of sintilimab-induced cystitis/ureteritis and summarized sintilimab-related adverse events to improve the assessment and management of irAEs.

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Management of Hematologic Adverse Events Associated With Immune Checkpoint Inhibitors

Journal of the Advanced Practitioner in Oncology ◽

10.6004/jadpro.2021.12.4.4 ◽

2021 ◽

Vol 12 (4) ◽

Author(s):

Barbara Barnes Rogers, CRNP, MN, AOCN, ANP-BC ◽

Carolyn Zawislak, MPAS, PA-C ◽

Victoria Wong, PA-C

Keyword(s):

Cell Death ◽

Programmed Cell Death ◽

Adverse Events ◽

Immune Checkpoint ◽

Blood Cells ◽

Immune Checkpoint Inhibitors ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

White Blood Cells ◽

Activated T Cells

Immune checkpoint inhibitors target suppressor receptors, including cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death ligand 1 (PD-L1). The activated T cells are not antigen specific; therefore, the blockade of the immune checkpoint may result in the development of autoimmune adverse events. The most common immune-related adverse events (irAEs) are rash, colitis, and endocrinopathies. However, irAEs that affect the hematologic system are rare and can affect red blood cells (e.g., autoimmune hemolytic anemia), white blood cells, and platelets (e.g., immune thrombocytopenia). Usually one cell line is affected; however, in some cases, multiple cell lines can be affected. Other changes in the hematologic system can also be affected (e.g., cryoglobulinemia, cytokine release syndrome). Due to the rarity and lack of recognition of these AEs, the timing, spectrum of events, and clinical presentation are poorly understood. Management of hematologic irAEs usually involves the use of steroids; however, other agents (e.g., IVIG, cyclosporine, rituximab) or procedures (e.g., plasma exchange, transfusions) can also be used.

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Impact of radiotherapy on risk of adverse events in patients receiving immunotherapy: A U.S. Food and Drug Administration pooled analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.3018 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 3018-3018

Author(s):

Mitchell Steven Anscher ◽

Shaily Arora ◽

Chana Weinstock ◽

Rachael Lubitz ◽

Anup Amatya ◽

...

Keyword(s):

Adverse Events ◽

Inflammatory Responses ◽

Checkpoint Inhibitors ◽

Pooled Analysis ◽

Hematologic Toxicity ◽

Pooled Data ◽

Advanced Malignancies ◽

Prospective Trials ◽

Grade 3 ◽

The Impact

3018 Background: Immune checkpoint inhibitors (ICIs) are widely used in the treatment of multiple advanced malignancies. Radiotherapy (RT) has been used in combination with ICIs to activate tumor-specific T cell responses, and RT also promotes non-specific acute and chronic inflammatory responses both locally and systemically. More than 50% of patients receive RT at some point during their course of cancer therapy, and relatively little information is available pertaining to the impact of RT, if any, on the risk of adverse events (AEs) in patients receiving ICIs. Methods: Pooled data from prospective trials of ICIs submitted to the FDA in initial or supplemental BLAs or NDAs through 12/2019 were included (N=66). Trials from applications that were withdrawn or not approved were not included. Patients were subdivided by whether or not radiotherapy was administered at any time during the course of their cancer treatment. AEs common to both ICI treatment and RT were identified to focus on the following reactions: neutropenia, thrombocytopenia, colitis, hepatitis, pneumonitis, and myocarditis. Descriptive statistics were used to examine AEs associated with the use of radiation and ICIs. Results: A total of 25,836 patients were identified, of which 9087 (35%) received RT and 16,749 (65%) did not. Radiation was associated with similar rates of AEs overall with numerically higher hematologic toxicities and pneumonitis and numerically lower colitis, hepatitis and myocarditis (Table). Patients receiving RT were more likely to experience Grade 3-5 hematologic toxicities compared to those not receiving RT. Conclusions: To our knowledge, this is the largest report of AE risk associated with the use of radiation and ICIs. Our results show that the incidence of hematologic toxicity and pneumonitis in patients receiving RT may be slightly higher. Analysis to determine comparability of baseline demographic characteristics, comprehensive AE profile, and timing of RT is underway. [Table: see text]

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Intestinal Microbiome Associated With Immune-Related Adverse Events for Patients Treated With Anti-PD-1 Inhibitors, a Real-World Study

Frontiers in Immunology ◽

10.3389/fimmu.2021.756872 ◽

2021 ◽

Vol 12 ◽

Author(s):

Wenhui Liu ◽

Fang Ma ◽

Bao Sun ◽

Yiping Liu ◽

Haoneng Tang ◽

...

Keyword(s):

Adverse Events ◽

Checkpoint Inhibitors ◽

Predictive Biomarkers ◽

Intestinal Bacteria ◽

Classification Model ◽

Intestinal Microbiome ◽

Fecal Samples ◽

Microbial Biomarkers ◽

Advanced Malignancies ◽

Auc Value

AimImmune checkpoint inhibitors (ICIs) have updated the treatment landscape for patients with advanced malignancies, while their clinical prospect was hindered by severe immune-related adverse events (irAEs). The aim of this study was to research the association between gut microbiome diversity and the occurrence of ICI-induced irAEs.Patients and MethodWe prospectively obtained the baseline fecal samples and clinical data from patients treated with anti-PD-1 inhibitors as monotherapy or in combination with chemotherapy or antiangiogenesis regardless of treatment lines. The 16S rRNA V3-V4 sequencing was used to test the gene amplicons of fecal samples. The development of irAEs was evaluated and monitored from the beginning of therapy based on CTCAE V5.01.ResultsA total of 150 patients were included in the study and followed up for at least 6 months. A total of 90 (60%) patients developed at least one type of adverse effect, among which mild irAEs (grades 1–2) occurred in 65 patients (72.22%) and severe irAEs (grades 3–5) in 25 patients (27.78%). Patients with severe irAEs showed a visible higher abundance of Streptococcus, Paecalibacterium, and Stenotrophomonas, and patients with mild irAEs had a higher abundance of Faecalibacterium and unidentified_Lachnospiraceae. With the aid of a classification model constructed with 5 microbial biomarkers, patients without irAEs were successfully distinguished from those with severe irAEs (AUC value was 0.66).ConclusionCertain intestinal bacteria can effectively distinguish patients without irAEs from patients with severe irAEs and provide evidence of gut microbiota as an informative source for developing predictive biomarkers to predict the occurrence of irAEs.

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Two Cases of Small Cell Cancer of the Maxillary Sinus Treated with Cisplatin plus Irinotecan and Radiotherapy

Case Reports in Otolaryngology ◽

10.1155/2013/893638 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 2

Author(s):

Kiyoaki Tsukahara ◽

Kazuhiro Nakamura ◽

Ray Motohashi ◽

Hiroki Sato

Keyword(s):

Adverse Events ◽

Oral Mucositis ◽

Blood Cells ◽

Cell Cancer ◽

White Blood Cells ◽

Stage Iv ◽

Small Cell ◽

The Body ◽

Small Cell Cancer ◽

Stage Iv Cancer

Background. Small cell carcinoma (SmCC) in the nasal cavity and paranasal sinuses is very rare, and definitive therapies have not yet been established.Methods. Chemoradiotherapy comprised 60 Gy of external radiation, with the administration of irinotecan intravenously at 60 mg/m2on days 1, 8, and 15 and cisplatin at 60 mg/m2on day 1.Results. Case 1 involved a 66-year-old woman with stage III cancer. Adverse events included decreased white blood cells, anemia, and oral mucositis, all Grade 2. The patient remained free of cancer as of 3 years and 6 months after completing the treatment. Case 2 involved a 60-year-old man with stage IV cancer. He also experienced adverse events of decreased white blood cells, anemia, and oral mucositis, all Grade 2. He died after 11 months due to metastases throughout the body.Conclusions. The results suggest that this regimen may be tolerable as a therapy for this type of carcinoma.

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How we treat neurological toxicity from immune checkpoint inhibitors

ESMO Open ◽

10.1136/esmoopen-2019-000540 ◽

2019 ◽

Vol 4 (Suppl 4) ◽

pp. e000540 ◽

Cited By ~ 4

Author(s):

Lavinia Spain ◽

Zayd Tippu ◽

James M Larkin ◽

Aisling Carr ◽

Samra Turajlic

Keyword(s):

Adverse Events ◽

Immune Checkpoint ◽

Cytotoxic T Lymphocyte ◽

Checkpoint Inhibitors ◽

Death Receptor ◽

Treatment Strategies ◽

Presenting Symptoms ◽

Programmed Death ◽

Symptoms And Signs ◽

Substantial Morbidity

Neurological adverse events from immune checkpoint inhibition are increasingly recognised, especially with combination anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) and anti-programmed death receptor 1 (anti-PD-1) therapies. Their presenting symptoms and signs are often subacute and highly variable, reflecting the numerous components of the nervous system. Given the risk of substantial morbidity and mortality, it is important to inform patients of symptoms that may be of concern, and to assess any suspected toxicity promptly. As with other immune-related adverse events, the cornerstone of management is administration of corticosteroids. Specialist neurology input is vital in this group of patients to guide appropriate investigations and tailor treatment strategies.

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A Rare Presentation of Checkpoint Inhibitor Induced Distal RTA

Case Reports in Oncological Medicine ◽

10.1155/2021/7406911 ◽

2021 ◽

Vol 2021 ◽

pp. 1-5

Author(s):

Andrew V. Doodnauth ◽

Miriam M. Klar ◽

Zohra R. Malik ◽

Krunal H. Patel ◽

Samy I. McFarlane

Keyword(s):

Adverse Events ◽

Renal Tubular Acidosis ◽

Checkpoint Inhibitors ◽

Acute Interstitial Nephritis ◽

Rare Presentation ◽

New Era ◽

Advanced Malignancies ◽

Small Incidence ◽

History Of ◽

Renal Tubular

Immune checkpoint inhibitors have opened a new era in treating advanced malignancies, resulting in a rapid increase in utilization, given the remarkable clinical outcomes. The incidence of immune-related adverse events increased due to the immunologic effects of these therapeutic agents. However, immune-related renal adverse events remain low, representing only a small incidence of reported cases. Common renal toxicity described includes acute interstitial nephritis, minimal change disease, and immune complex glomerulonephritis. Renal tubular acidosis has occasionally been reported but is highly uncommon. This report presents a case of a 68-year-old woman with a known history of metastatic melanoma undergoing treatment with ipilimumab+nivolumab, who developed distal renal tubular acidosis requiring stress dose steroids and sodium bicarbonate for treatment. We describe the clinical characteristics, potential mechanisms, and management of this case, highlighting the need among clinicians utilizing immune check inhibitors to be aware of this immune-related disease entity.

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Automated Identification of Patients with Immune-related Adverse Events from Clinical Notes using Word embedding and Machine Learning

10.1101/2020.05.19.20106583 ◽

2020 ◽

Author(s):

Samir Gupta ◽

Anas Belouali ◽

Neil J Shah ◽

Michael B Atkins ◽

Subha Madhavan

Keyword(s):

Machine Learning ◽

Adverse Events ◽

Checkpoint Inhibitors ◽

High Accuracy ◽

Automated Identification ◽

Real World Data ◽

Clinical Notes ◽

Safety Research ◽

Advanced Malignancies ◽

Treatment Safety

Immune Checkpoint Inhibitors (ICIs) have substantially improved survival in patients with advanced malignancies. However, ICIs are associated with a unique spectrum of side effects termed Immune-Related Adverse Events (irAEs). To ensure treatment safety, research efforts are needed to comprehensively detect and understand irAEs from real world data (RWD). The goal of this work is to evaluate a Machine Learning-based phenotyping approach that can identify patients with irAEs from a large volume of retrospective clinical notes representing RWD. Evaluation shows promising results with an average F1-score=0.75 and AUC-ROC=0.78. While the extraction of any available irAEs in charts achieves high accuracy, individual irAEs extraction has room for further improvement.

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Ultrastructural changes in murine lymphoma cells exposed to ultraviolet-A radiation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010008482x ◽

1991 ◽

Vol 49 ◽

pp. 104-105

Author(s):

Delma P. Thomas ◽

Dianne E. Godar

Keyword(s):

Medical Devices ◽

Blood Cells ◽

White Blood Cells ◽

Consumer Products ◽

Ultrastructural Changes ◽

Ultraviolet A ◽

Uv Spectrum ◽

Lymphoma Cells ◽

Murine Lymphoma ◽

Transmission Electron

Ultraviolet radiation (UVR) from all three waveband regions of the UV spectrum, UVA (320-400 nm), UVB (290-320 nm), and UVC (200-290 nm), can be emitted by some medical devices and consumer products. Sunlamps can expose the blood to a considerable amount of UVR, particularly UVA and/or UVB. The percent transmission of each waveband through the epidermis to the dermis, which contains blood, increases in the order of increasing wavelength: UVC (10%) < UVB (20%) < UVA (30%). To investigate the effects of UVR on white blood cells, we chose transmission electron microscopy to examine the ultrastructure changes in L5178Y-R murine lymphoma cells.

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The Effect of Red Blood Cells on the ADP-induced Aggregation of Human Platelets in Flow Through Tubes

Thrombosis and Haemostasis ◽

10.1055/s-0038-1645696 ◽

1990 ◽

Vol 63 (01) ◽

pp. 112-121 ◽

Cited By ~ 18

Author(s):

David N Bell ◽

Samira Spain ◽

Harry L Goldsmith

Keyword(s):

Platelet Aggregation ◽

Shear Rate ◽

Red Blood Cells ◽

Blood Cells ◽

Platelet Rich Plasma ◽

Mean Transit Time ◽

White Blood Cells ◽

Aggregate Size ◽

Human Platelets ◽

Induced Aggregation

SummaryThe effect of red blood cells, rbc, and shear rate on the ADPinduced aggregation of platelets in whole blood, WB, flowing through polyethylene tubing was studied using a previously described technique (1). Effluent WB was collected into 0.5% glutaraldehyde and the red blood cells removed by centrifugation through Percoll. At 23°C the rate of single platelet aggregtion was upt to 9× greater in WB than previously found in platelet-rich plasma (2) at mean tube shear rates Ḡ = 41.9,335, and 1,920 s−1, and at both 0.2 and 1.0 µM ADP. At 0.2 pM ADP, the rate of aggregation was greatest at Ḡ = 41.9 s−1 over the first 1.7 s mean transit time through the flow tube, t, but decreased steadily with time. At Ḡ ≥335 s−1 the rate of aggregation increased between t = 1.7 and 8.6 s; however, aggregate size decreased with increasing shear rate. At 1.0 µM ADP, the initial rate of single platelet aggregation was still highest at Ḡ = 41.9 s1 where large aggregates up to several millimeters in diameter containing rbc formed by t = 43 s. At this ADP concentration, aggregate size was still limited at Ḡ ≥335 s−1 but the rate of single platelet aggregation was markedly greater than at 0.2 pM ADP. By t = 43 s, no single platelets remained and rbc were not incorporated into aggregates. Although aggregate size increased slowly, large aggregates eventually formed. White blood cells were not significantly incorporated into aggregates at any shear rate or ADP concentration. Since the present technique did not induce platelet thromboxane A2 formation or cause cell lysis, these experiments provide evidence for a purely mechanical effect of rbc in augmenting platelet aggregation in WB.

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