scholarly journals Immune Checkpoint Inhibitor Nephrotoxicity: Update 2020

Kidney360 ◽  
2020 ◽  
Vol 1 (2) ◽  
pp. 130-140 ◽  
Author(s):  
Shruti Gupta ◽  
Frank B. Cortazar ◽  
Leonardo V. Riella ◽  
David E. Leaf
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Solid Organ Transplantation ◽  
Treatment Strategies ◽  
Solid Organ ◽  
Diagnostic Uncertainty ◽  
Patients With Cancer ◽  
Underlying Malignancy

Immune checkpoint inhibitors (ICPIs) have transformed the landscape of oncology, but are associated with a variety of autoimmune adverse events, including AKI. ICPI-associated AKI (ICPI-AKI) is emerging as an increasingly frequent cause of AKI in patients with cancer, and poses unique diagnostic and management challenges to clinicians who care for these patients. In this review, we describe the incidence and risk factors for ICPI-AKI, including proton pump inhibitor use, CKD, and combination immunotherapy. We discuss the limitations of the various definitions used for ICPI-AKI in prior studies, and propose a novel classification system (definite, probable, and possible ICPI-AKI) that recognizes the diagnostic uncertainty inherent in many cases. We discuss the key clinicopathologic features and treatment strategies for ICPI-AKI, including the role of kidney biopsy versus empirical treatment with steroids. We also explore the under-studied area of ICPI use in the setting of solid organ transplantation, where nephrologists and oncologists must balance the risk of rejection versus treating the underlying malignancy. Finally, we summarize existing data on the role of ICPI rechallenge after an episode of ICPI-AKI.

scholarly journals Safety of Influenza Vaccine in Patients With Cancer Receiving Pembrolizumab

2020 ◽  
Vol 16 (7) ◽  
pp. e573-e580 ◽  
Author(s):  
Jarrett J. Failing ◽  
Thanh P. Ho ◽  
Siddhartha Yadav ◽  
Neil Majithia ◽  
Irbaz Bin Riaz ◽  
...  
Keyword(s):  
Influenza Vaccination ◽  
Immune Checkpoint ◽  
Medical Records ◽  
Patient Population ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Patients With Cancer ◽  
Cumulative Incidence Curve ◽  
Checkpoint Inhibitor Therapy ◽  
Multivariable Analyses

PURPOSE: There is a concern that influenza vaccination could increase the incidence of immune-related adverse events (irAEs) in patients with cancer receiving immune checkpoint inhibitors. The aim of our study was to determine the safety of influenza vaccination in this patient population. PATIENTS AND METHODS: We retrospectively identified patients who received at least 1 dose of pembrolizumab during any influenza season from September 2014 to August 2017 and reviewed medical records for irAEs. The primary endpoint was the incidence of irAEs. We used multivariable logistic regression and cumulative incidence curve with competing risks for comparison. RESULTS: Among 162 patients with cancer included in this study, 70 patients (43.2%) received at least 1 influenza vaccination. The vaccinated group was significantly older ( P = .002) and received more cycles of pembrolizumab ( P = .006). The incidence of any grade irAEs in the vaccinated group trended toward being lower (25.7% v 40.2%; P = .07) compared with the nonvaccinated group. Influenza vaccination was independently associated with fewer irAEs, with an odds ratio of 0.4 (95% CI, 0.2 to 0.9; P = .03) in multivariable analyses. The vaccinated group was less likely to have irAEs compared with the nonvaccinated group (24.7% v 34.4% at 12 months; P = .05), with death as a competing risk. The median irAE-free duration in the vaccinated group was longer than the nonvaccinated group (not reached v 28 months; P = .037). CONCLUSION: Influenza vaccination in patients with cancer receiving immune checkpoint inhibitor therapy was not associated with increased irAEs. This supports the safety of influenza vaccination in this patient population.

scholarly journals The Efficacy and Safety of Immune Checkpoint Inhibitors in Patients With Cancer and Preexisting Autoimmune Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Hui Tang ◽  
Jianfeng Zhou ◽  
Chunmei Bai
Keyword(s):  
Autoimmune Disease ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Close Monitoring ◽  
Tumor Type ◽  
Patients With Cancer ◽  
High Benefit

Immune checkpoint inhibitor (ICI) is a revolutionary breakthrough in the field of cancer treatment. Because of dysregulated activation of the immune system, patients with autoimmune disease (AID) are usually excluded from ICI clinical trials. Due to a large number of cancer patients with preexisting AID, the safety and efficacy of ICIs in these patients deserve more attention. This review summarizes and analyzes the data regarding ICI therapy in cancer patients with preexisting AID from 17 published studies. Available data suggests that the efficacy of ICIs in AID patients is comparable to that in the general population, and the incidence of immune-related adverse events (irAEs) is higher but still manageable. It is recommended to administer ICIs with close monitoring of irAEs in patients with a possibly high benefit-risk ratio after a multidisciplinary discussion based on the patient’s AID category and severity, the patient’s tumor type and prognosis, alternative treatment options, and the patient’s intention. Besides, the prevention and management of irAEs in AID patients have been discussed.

scholarly journals Acute kidney injury in patients treated with immune checkpoint inhibitors

2021 ◽  
Vol 9 (10) ◽  
pp. e003467
Author(s):  
Shruti Gupta ◽  
Samuel A P Short ◽  
Meghan E Sise ◽  
Jason M Prosek ◽  
Sethu M Madhavan ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Kidney Biopsy ◽  
Checkpoint Inhibitors ◽  
Cox Model ◽  
Kidney Injury ◽  
Renal Recovery ◽  
Patients With Cancer ◽  
Lower Baseline

BackgroundImmune checkpoint inhibitor-associated acute kidney injury (ICPi-AKI) has emerged as an important toxicity among patients with cancer.MethodsWe collected data on 429 patients with ICPi-AKI and 429 control patients who received ICPis contemporaneously but who did not develop ICPi-AKI from 30 sites in 10 countries. Multivariable logistic regression was used to identify predictors of ICPi-AKI and its recovery. A multivariable Cox model was used to estimate the effect of ICPi rechallenge versus no rechallenge on survival following ICPi-AKI.ResultsICPi-AKI occurred at a median of 16 weeks (IQR 8–32) following ICPi initiation. Lower baseline estimated glomerular filtration rate, proton pump inhibitor (PPI) use, and extrarenal immune-related adverse events (irAEs) were each associated with a higher risk of ICPi-AKI. Acute tubulointerstitial nephritis was the most common lesion on kidney biopsy (125/151 biopsied patients [82.7%]). Renal recovery occurred in 276 patients (64.3%) at a median of 7 weeks (IQR 3–10) following ICPi-AKI. Treatment with corticosteroids within 14 days following ICPi-AKI diagnosis was associated with higher odds of renal recovery (adjusted OR 2.64; 95% CI 1.58 to 4.41). Among patients treated with corticosteroids, early initiation of corticosteroids (within 3 days of ICPi-AKI) was associated with a higher odds of renal recovery compared with later initiation (more than 3 days following ICPi-AKI) (adjusted OR 2.09; 95% CI 1.16 to 3.79). Of 121 patients rechallenged, 20 (16.5%) developed recurrent ICPi-AKI. There was no difference in survival among patients rechallenged versus those not rechallenged following ICPi-AKI.ConclusionsPatients who developed ICPi-AKI were more likely to have impaired renal function at baseline, use a PPI, and have extrarenal irAEs. Two-thirds of patients had renal recovery following ICPi-AKI. Treatment with corticosteroids was associated with improved renal recovery.

scholarly journals Targeting nuclear acid-mediated immunity in cancer immune checkpoint inhibitor therapies

2020 ◽  
Vol 5 (1) ◽  
Author(s):  
Miaoqin Chen ◽  
Shiman Hu ◽  
Yiling Li ◽  
Ting Ting Jiang ◽  
Hongchuan Jin ◽  
...  
Keyword(s):  
Cancer Immunotherapy ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Immune Checkpoint Inhibitor ◽  
Cell Function ◽  
Checkpoint Inhibitors ◽  
Critical Role ◽  
Tumor Control ◽  
New Strategies

AbstractCancer immunotherapy especially immune checkpoint inhibition has achieved unprecedented successes in cancer treatment. However, there are many patients who failed to benefit from these therapies, highlighting the need for new combinations to increase the clinical efficacy of immune checkpoint inhibitors. In this review, we summarized the latest discoveries on the combination of nucleic acid-sensing immunity and immune checkpoint inhibitors in cancer immunotherapy. Given the critical role of nuclear acid-mediated immunity in maintaining the activation of T cell function, it seems that harnessing the nuclear acid-mediated immunity opens up new strategies to enhance the effect of immune checkpoint inhibitors for tumor control.

scholarly journals New emerging targets in cancer immunotherapy: the role of TIM3

ESMO Open ◽  
2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. e000497 ◽  
Author(s):  
Alex Friedlaender ◽  
Alfredo Addeo ◽  
Giuseppe Banna
Keyword(s):  
Immune Checkpoint ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Treatment Strategies ◽  
Lung Cancer Patients ◽  
Programmed Death ◽  
Programmed Death 1 ◽  
Cancer Types ◽  
Domain 3

Currently, the programmed death-1/programmed death ligand-1 and the cytotoxic T-lymphocyte-associated protein 4 are the two commonly targeted immune-checkpoint inhibition pathways. These drugs have significantly improved the prognosis of many cancer types. While immune-checkpoint inhibitors have revolutionised the treatment of many cancer types, the majority of patients still progress. Several treatment strategies have been pursued to improve current results. One approach is to combine two checkpoint inhibitors, currently with promising results in melanoma, renal cell carcinoma and a subset of non-small-cell lung cancer patients. The identification of new checkpoint targets could allow the field of immuno-oncology to evolve further. We will discuss one of the most promising immune-checkpoint targets currently under investigation, the T-cell immunoglobulin and mucin domain-3.

Molecular profiling of appendix-derived pseudomyxoma peritonei (PMP).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 571-571 ◽  
Author(s):  
Elizabeth Gleeson ◽  
Rebecca Feldman ◽  
Sherri Z. Millis ◽  
Beth Mapow ◽  
Lynn Mackovick ◽  
...  
Keyword(s):  
Protein Expression ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Tumor Infiltrating Lymphocytes ◽  
Molecular Profiling ◽  
Low Frequencies ◽  
Rare Malignancy

571 Background: PMP is a rare malignancy originating from the appendix, characterized by disseminated mucinous tumor implants on peritoneal surfaces. Cytoreductive surgery and intraperitoneal chemotherapy offers optimal outcomes for most patients; however, for patients that progress, there are few treatment options. We examined the role of multiplatform molecular profiling to study biomarker-guided treatment strategies for this rare malignancy. Methods: 54 patients with appendix-derived PMP were included in the study and tested centrally at Caris Life Sciences (Phoenix, AZ). Tests included one or more of the following: gene sequencing (Sanger or next generation sequencing [NGS]), protein expression (immunohistochemistry [IHC]) and gene amplification (C/FISH). Results: Targeted sequencing of 47 genes detected variants in KRAS (79%), GNAS (73%) and SMAD4 (18%). Mutations were found at low frequencies (n = 1-2) in APC, ATM, BRAF, PIK3CA, MLH1 and TP53. GNAS and KRAS co-occurrence was found in 38%. High rates of protein overexpression were found in EGFR (83%), cMET (59%), cKIT (58%) and PDGFRA (58%), respectively. Immune checkpoint expression was found in 36% (PD1-positive tumor infiltrating lymphocytes) and 9% (PDL1 tumor expression). Expression of surrogate markers of cell proliferation were found at low rates (TLE3 27%, TOP2A 22%), consistent with the slow-growing biology of PMP. PTEN was intact (wild type [100%] and positive IHC [80%]) in the majority of PMP. Patients exhibit stable microsatellite status and mismatch repair proficiency in 93% of patients. Importantly, multidrug resistance protein expression was found at high levels (100% BCRP, 94% MRP1, 88% PGP). Markers for gemcitabine (RRM1), fluorouracil (TS), oxaliplatin (ERCC1) and irinotecan (TOPO1) chemo-sensitivities were found to be favorable in 93%, 87%, 77% and 65%, respectively. Conclusions: Molecular profiling by multiple platforms identified potential therapy options in the non-targetable setting of a KRAS-mutated population. The role of cMET-targeted therapies and immune checkpoint inhibitors merit further investigation. Biomarker-guided selection of cytotoxic chemotherapies may facilitate responses to systemic treatment.

scholarly journals The immunotherapy revolution in genitourinary malignancies

Immunotherapy ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 819-831
Author(s):  
Shruti U Gandhy ◽  
Ravi A Madan ◽  
Jeanny B Aragon-Ching
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitor ◽  
Checkpoint Inhibitors ◽  
Cell Cancer ◽  
Treatment Modalities ◽  
Metastatic Setting ◽  
Cancer Types ◽  
Therapeutic Cancer Vaccines ◽  
Demonstrate Survival Benefit

Immune checkpoint inhibitor (ICI) therapy and therapeutic cancer vaccines have continued to demonstrate survival benefit and durable clinical response in patients with renal cell cancer, prostate cancer and bladder cancer, with limited responses in testicular cancer. The role of immunotherapy in combination with chemotherapy or other targeted therapies in the neo-adjuvant, adjuvant and metastatic setting is actively being explored. We describe the current immunotherapy-related treatment modalities approved for genitourinary cancers, focusing on immune checkpoint inhibitors, vaccines and other modalities, and highlight ongoing studies involving immunotherapy in these cancer types.

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