Immune-related adverse events in advanced NSCLC treated with immunotherapy alone or concurrent chemotherapy and immunotherapy.

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 83-83
Author(s):  
John Melson ◽  
Daniel Reed ◽  
Bethany J. Horton ◽  
Margaret Moore ◽  
Jacqueline Theresa Brown ◽  
...  
Keyword(s):  
Adverse Events ◽  
Proportional Hazards ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Therapy Group ◽  
Stage Iv ◽  
Standard Of Care ◽  
Concurrent Chemotherapy ◽  
Increased Risk ◽  
Treatment Naïve

83 Background: Concurrent chemotherapy (CTX) with checkpoint inhibitors (CPI) has become a new standard of care for treatment naïve stage IV non-small cell lung cancer (NSCLC). Little is known about the timing and pattern of immune-related adverse events (irAEs) when CTX and CPI are combined. We sought to characterize irAEs and determine if combination CTX+CPI affects time to first irAE in comparison to patients (pts) receiving CPI alone. Methods: Advanced NSCLC patients who received at least one dose of a CPI at our institution between 2015 and 2018, either alone or with CTX, were identified. Retrospective review for occurrence of irAEs and clinical outcomes was performed. Proportional hazards models were used to assess time to first irAE for CPI vs CTX+CPI and overall survival (OS) for CPI alone. Results: 149 pts were identified. 112 pts received CPI alone and 37 received CTX+CPI. The proportion of pts with at least 1 irAE was higher in the combination therapy group than the monotherapy group (59% vs 34% of patients). Time to any grade first irAE was shorter with CTX+CPI vs CPI alone (6.0 m vs 36.7 m, HR 1.8, p = 0.0304). Among pts treated with CPI alone, OS was significantly longer with any irAE (38.0 m vs 11.4 m, HR 2.9, p = 0.0026). While there were more irAEs in the CTX+CPI cohort, the frequency of irAEs by organ system was similar to previous reports. Conclusions: For patients receiving CTX+CPI, there is an increased risk of irAEs and a significantly shorter time to first irAE occurrence compared to CPI alone. Among patients receiving CPI alone, the presence of irAE was associated with a 3-fold improvement in OS. Further analysis of OS for the CTX+CPI group is planned with additional follow-up. [Table: see text]

scholarly journals Circulating regulatory T cells predict efficacy and atypical responses in lung cancer patients treated with PD-1/PD-L1 inhibitors

2021 ◽  
Author(s):  
Da Hyun Kang ◽  
Chaeuk Chung ◽  
Pureum Sun ◽  
Da Hye Lee ◽  
Song-I Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Advanced Nsclc ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Treg Cells ◽  
University Hospital ◽  
X Rays ◽  
Lung Cancer Patients ◽  
National University

Abstract Background Immune checkpoint inhibitors (ICIs) have become the standard of care for a variety of cancers, including non-small cell lung cancer (NSCLC). In this study, we investigated the frequency of pseudoprogression and hyperprogression in lung cancer patients treated with ICIs in the real world and aimed to discover a novel candidate marker to distinguish pseudoprogression from hyperprogression soon after ICI treatment. Methods This study included 74 patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors at Chungnam National University Hospital (CNUH) between January 2018 and August 2020. Chest X-rays were examined on day 7 after the first ICI dose to identify changes in the primary mass, and the response was assessed by computed tomography (CT). We evaluated circulating regulatory T (Treg) cells using flow cytometry and correlated the findings with clinical outcomes. Results The incidence of pseudoprogression was 13.5%, and that of hyperprogression was 8.1%. On day 7 after initiation of treatment, the frequency of CD4+CD25+CD127loFoxP3+ Treg cells was significantly decreased compared with baseline (P = 0.038) in patients who experienced pseudoprogression and significantly increased compared with baseline (P = 0.024) in patients who experienced hyperprogression. In the responder group, the frequencies of CD4+CD25+CD127loFoxP3+ Treg cells and PD-1+CD4+CD25+CD127loFoxP3+ Treg cells were significantly decreased 7 days after commencement of treatment compared with baseline (P = 0.034 and P < 0.001, respectively). Conclusion Circulating Treg cells represent a promising potential dynamic biomarker to predict efficacy and differentiate atypical responses, including pseudoprogression and hyperprogression, after immunotherapy in patients with NSCLC.

The combination of EGFR-TKIs and anlotinib as a first-line therapy for EGFR-mutant advanced non-small cell lung cancer: A multicenter, single-arm, phase II clinical trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9030-9030
Author(s):  
Zhiyong He ◽  
Jinghui Lin ◽  
Yueming He ◽  
Jing Zhang ◽  
Dongyong Yang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Adverse Events ◽  
Advanced Nsclc ◽  
De Novo ◽  
Egfr Mutations ◽  
Treatment Naïve ◽  
Pre Treatment ◽  
Egfr Mutant ◽  
Nsclc Patients ◽  
Egfr Tkis

9030 Background: Currently,EGFR-TKIs are widely accepted as the standard treatment for EGFR- mutant advanced non-small-cell lung cancer (NSCLC); however, acquired resistance is inevitable. Combination therapy is considered as a strategy to overcome the resistance to EGFR-TKIs. Anlotinib, a novel multi-targeting, small-molecule TKI, has shown active to suppress tumor angiogenesis and growth. However, there is still a lack of evidence supporting the use of EGFR-TKIs in combination with anlotinib for the treatment of NSCLC until now. A multi-center, single-arm, phase II clinical trial was therefore designed to examine the efficacy and safety of EGFR-TKIs combined with anlotinib for treatment-naïve, advanced NSCLC patients, and unravel the possible mechanisms. Methods: This study was conducted in 14 research centers in Fujian, China. The main eligibility criteria were stage IV or relapsed nonsquamous NSCLC with EGFR mutations (exon 19 deletion,, and L858R), ECOG score 0-2,and age 20 to 75 years and no previous systemic treatment. Patients with asymptomatic brain metastases were admitted.Eligible patients were given gefitinib (250 mg QD) or icotinib (125 mg TID) in combination with anlotinib (10 mg per day, on days 1‒14; 21 days per cycle) until disease progression. The primary endpoint is progression-free survival (PFS) and safety, and the secondary endpoint is overall survival (OS), objective response rate (ORR) and disease control rate (DCR).Peripheral blood was sampled pre-treatment, once every two months during treatment and after disease progression, and T790M mutation was detected in plasma ctDNA using a droplet digital PCR (ddPCR) assay. Results: Of 60 patients enrolled (August 2, 2018 to May 28, 2020). As of February 1, 2021, 37 patients (61.7%) experienced PFS events and 10 (16.7%) died. The ORR was 78.3%, and the DCR was100%.Median PFS was 13.0 months (95%CI,10.7-15.3).The 5 most common treatment-related adverse events included rash (63.3%), fatigue (55.0%), hypertension (48.3%), diarrhea (33.3%) and hand-foot syndrome (30.0%), and grade 3 adverse events included hypertension (5.0%), rash (1.67%), hypertriglyceridemia (1.67%), vomiting (1.67%) and elevated ALT (1.67%); no grade 4 adverse events or drug-related deaths were observed. Peripheral blood samples were collected from 36 patients pre-treatment, and 30.6% were identified with low-frequency de novo T790M mutations, with the mutation-allele frequency (MAF) ranging from 0.01% to 0.28%. Conclusions: The combination of the first-generation EGFR-TKIs and anlotinib shows impressive ORR and DCR, and acceptable toxicity in treatment-naïve advanced NSCLC patients with activating EGFR mutations, and we observed a high proportion of patients harboring de novo EGFR T790M mutations in this study. Clinical trial information: NCT03720873.

Safety and efficacy of nivolumab plus recombinant human endostatin in previously treated advanced non-small cell lung cancer: A prospective and multicenter phase 2 trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21079-e21079
Author(s):  
Weize Lv ◽  
Beilong Zhong ◽  
Wenhua Zhao ◽  
Zhong Lin ◽  
Xiaofeng Pei ◽  
...  
Keyword(s):  
Adverse Events ◽  
Advanced Nsclc ◽  
Response Rate ◽  
Checkpoint Inhibitors ◽  
Objective Response ◽  
Efficacy And Safety ◽  
Small Cell Lung ◽  
First Line ◽  
Recombinant Human Endostatin ◽  
Phase 2 Trial

e21079 Background: Although the administration of immune checkpoint inhibitors (ICIs) and antiangiogenic agents in advanced non–small-cell lung cancer (NSCLC) has been well established, evidence supporting the combination of immune checkpoint inhibitors plus antiangiogenic drugs in previous treatment patients with advanced NSCLC is insufficient. We aimed to investigate the efficacy and safety of nivolumab combined with recombinant human endostatin (rh-Endostatin) as second-line or later treatment for advanced NSCLC. Methods: In this prospective and multicentre phase 2 trial we enrolled patients with advanced NSCLC who had not responded to standardized first-line treatment regimen from two cancer centres in China. Eligible patients were those aged 18-75 years without ICIs in first-line treatment who received nivolumab (3mg/kg, intravenous drip, day 1) every 2 weeks and rh-Endostatin (30 mg, 24-hour continous intravenous infusion，day 1–7) every 4 weeks till disease progression or discontinuation. The primary end points were objective response rate and safety. This study is registered with Chinese Clinical Trial Registry, number ChiCTR1900023664. Results: A total of 35 patients (median age, 60 years; range, 37-72 years) received nivolumab and rh-Endostatin. Median previous treated line of eligible patients was 2 lines (range, 1-7 lines). Patients received a median of 2 cycles of therapy (range, 1-14 cycles). Eleven of 33 evaluable patients achieved confirmed partial response with an objective response rate of 33.3% (11/33, 95% confidence interval [CI]: 17.2% – 49.4%) and disease control rate of 60.6% (20/33,95%CI:43.9%–77.3%). Median follow-up was 8.2 months (range: 0.9 –17.1). Median progression-free survival was 7.1 months (95% CI: 1.2m–13.0m), median overall survival was not reached and the 6-month overall survival rate was 54.5% (95% CI:37.6%–71.4%). The predominant grade 1-2 adverse events were thyroiditis, arrhythmia, hypertension. The grade 3 treatment-related adverse events were pneumonitis (3/35, 8.6%), hypertension (1/35, 2.9%) and atrial fibrillation (1/35, 2.9%), respectively. No grade 4 or 5 treatment-related adverse events were observed. Conclusions: To the best of our knowledge, this is the first prospective study that assessed nivolumab combined with rh-Endostatin as second-line or later treatment in pretreated patients with advanced NSCLC. In view of its encouraging efficacy and safety profile, nivolumab plus rh-Endostatin represents a promising treatment regimen in this patient population. Clinical trial information: ChiCTR1900023664.

scholarly journals Management of pulmonary toxicity associated with immune checkpoint inhibitors

2019 ◽  
Vol 28 (154) ◽  
pp. 190012 ◽  
Author(s):  
Myriam Delaunay ◽  
Grégoire Prévot ◽  
Samia Collot ◽  
Laurent Guilleminault ◽  
Alain Didier ◽  
...  
Keyword(s):  
Adverse Events ◽  
Immune Checkpoint ◽  
Pulmonary Toxicity ◽  
Immune Checkpoint Inhibitors ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Standard Of Care ◽  
Serious Adverse Events ◽  
Programmed Cell Death 1 ◽  
Life Threatening

Immunotherapy has become a standard of care in oncology, following the recent approvals of cytotoxic T-lymphocyte-associated protein-4 and programmed cell death-1 inhibitors in lung cancer, melanoma, renal cell carcinoma, Hodgkin's lymphoma, bladder, head and neck cancers. Besides their efficacy, these agents also generate specific immune-related adverse events. Due to the increasing prescription of immune-checkpoint inhibitors, the incidence of immune toxicity will continue to rise. The awareness of immune-related adverse events is key to ensuring both diagnosis and management of the possible serious adverse events. Although severe immune-related adverse events remain rare, they can lead to discontinued treatment or to death if they are not forecasted and managed properly. Even if lung toxicity is not the most frequent adverse event, it remains critical as it can be life-threatening. Herein, the main aspects of pulmonary toxicity are reviewed and guidelines are also proposed in order to manage the possible side-effects.

scholarly journals Immune-Related Adverse Events Requiring Hospitalization: Spectrum of Toxicity, Treatment, and Outcomes

2019 ◽  
Vol 15 (9) ◽  
pp. e825-e834 ◽  
Author(s):  
Aanika Balaji ◽  
Jiajia Zhang ◽  
Beatriz Wills ◽  
Kristen A. Marrone ◽  
Hany Elmariah ◽  
...  
Keyword(s):  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Patient Characteristics ◽  
Spectrum Management ◽  
Service Planning ◽  
Inpatient Service ◽  
High Demand ◽  
Academic Center ◽  
Increased Risk ◽  
Oncology Center

PURPOSE: Immune checkpoint inhibitors (ICIs) cause immune-related adverse events (irAEs). The proportion of patients who are hospitalized for irAEs and their spectrum, management, and outcomes are not well described. METHODS: We report the proportion of hospitalized patients in an academic center who were treated with ICIs from May to December 2017. Patient characteristics, toxicities, management, and outcomes for confirmed irAE admissions are reported. Associations between patient features and irAE hospitalizations are examined. RESULTS: Twenty-three percent (n = 100) of 443 patients who were admitted to an academic oncology center over 6 months had ever received ICIs. Of these patients, 41% were admitted for suspected irAEs and 23% were confirmed irAEs. IrAEs accounted for 5% of all oncology hospitalizations (n = 23). Ninety-one percent of patients with confirmed irAEs prompted a medicine subspecialist consultation, most commonly gastroenterology (22%). Fifteen patients (65%) had their irAEs improve/resolve, seven (30%) had worsening irAEs, and three (13%) died of their irAEs. The majority of patients (n = 20; 87%) discontinued ICIs after discharge. Among ICI-treated patients who required admission, an increased likelihood of irAE-related hospitalization was associated with patient age older than 65 years (odds ratio, 5.4; 95% CI, 1.6 to 17.8) and receipt of combination immunotherapy (OR, 6.8; 95% CI, 2.0 to 23.2). CONCLUSION: A notable proportion of ICI-treated patients are hospitalized for irAEs, and these patients have a high demand for multidisciplinary management. Older age and combination ICI treatment were associated with an increased risk of irAE-related hospitalization. Whereas these data are from an academic center and include patients in clinical trials, with expanding use of ICIs, these data have important implications for inpatient service planning and risk stratification.

Cisplatin(P)-including triplets versus P-free doublets in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC): SICOG 0101 randomized trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7103-7103 ◽  
Author(s):  
P. Comella ◽  
S. Palmeri ◽  
G. De Cataldis ◽  
G. Filippelli ◽  
R. Cioffi ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Locally Advanced ◽  
Stage Iv ◽  
Standard Of Care ◽  
Rank Test ◽  
Stage Iiia ◽  
Log Rank Test ◽  
Grade 3 ◽  
Metastatic Sites ◽  
Nsclc Patients

7103 Background: We previously reported that triplets with P-gemcitabine (G) plus vinorelbine (V) (PGV) or paclitaxel (T) (PGT) prolonged the survival (S) of advanced NSCLC patients (pts) in comparison with P-based doublets (PG or PV). Aims of the present study were: (1) to compare (log-rank test) the S of P-based triplets vs P-free doublets, and (2) to compare (Fisher test) safety and response rate (RR) of T- and V-regimens. Methods: A 2x2 factorial design was adopted. Pts aged ≤ 70 years, with PS (ECOG) < 2, inoperable stage IIIA, IIIB, or IV NSCLC were randomly treated with: GV = G 1,000 mg/m2 + V 25 mg/m2 on day (D) 1 and 8; GT = G 1,000 mg/m2 + T 125 mg/m2 on D 1 and 8; PGV = P 50 mg/m2 on D 1 and 8 + GV; PGT = P 50 mg/m2 on D 1 and 8 + GT. In all arms, cycles were repeated Q 3 weeks. Only responder pts after 3 cycles received further chemotherapy (CT). Thoracic RT was delivered after CT to pts with intra-thoracic disease. 330 events were required to have a 90% power to demonstrate (two-sided P < 0.05) a 30% reduction of hazard of death. Results: From April 2001 to December 2005, 431 pts were recruited in the 4 arms. Characteristics in % were well balanced in P-based triplets and P-free doublets: males, 84/91; PS 0, 25/23; squamous cell carcinoma, 38/42; weight loss, 22/29; stage IV, 66/65; CNS metastases, 5/8; ≥ 2 metastatic sites, 29/30. So far, 411 pts were assessed for response: RR of triplets vs doublets was 88/204 (43%) vs 68/207 (33%) (P = 0.020), and of T-based vs V-based regimens was 40% vs 36% (P = 0.218). To date, 313 deaths were registered: median and 1-year S were 10.6 mo. and 41% for pts treated with triplets, and 10.4 mo. and 39% for pts treated with doublets (P = 0.786). Over initial 3 courses, occurrence of grade ≥ 3 toxicity (T vs V, % pts) was: neutropenia, 18% vs 30% (P < 0.004); febrile neutropenia, 4% vs 7%; platelets, 7% vs 12% (P = 0.056); anemia, 5% vs 7%; vomiting, 1% vs 2%; diarrhea, 6% vs 3%; stomatitis, 3% vs 0.5%. Grade ≥ 2 neurotoxicity occurred in 1% of both groups. Conclusions: Activity was significantly higher with P-based triplets, but they did not affect the OS. T-based regimens were equally active and less toxic than V-based regimens. Therefore, the GT regimen may represent a new standard of care for advanced NSCLC pts. No significant financial relationships to disclose.

Long-term comparative toxicity of LDR versus HDR prostate brachytherapy ± EBRT and evaluation of risk hazard over time: A SEER-Medicare analysis.

2016 ◽  
Vol 34 (2_suppl) ◽  
pp. 108-108 ◽  
Author(s):  
Jonathan D. Tward ◽  
Stephanie Jarosek ◽  
Haitao Chu ◽  
Dennis C. Shrieve ◽  
Sean Elliott
Keyword(s):  
Adverse Events ◽  
Dose Rate ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Baseline Risk ◽  
High Dose ◽  
Radiation Toxicity ◽  
Prostate Brachytherapy ◽  
Increased Risk ◽  
Over Time

108 Background: Severe urinary adverse events (UAEs) include surgical treatment of urethral stricture, urinary incontinence and radiation cystitis. Our objective is to compare the incidence of late UAEs after low dose rate BT (LDR) and high dose rate BT (HDR) as well as LDR+EBRT and HDR+EBRT. Methods: We identified men treated with LDR (n=12,801), HDR (n=685), LDR+EBRT (8,518) and HDR+EBRT (n=2,392) from the SEER-Medicare Database. The populations were balanced by propensity weighting and the Kaplan-Meier incidence of severe UAEs was compared. Propensity-weighted Cox proportional hazards models were used to compare the adjusted hazard of UAEs. These UAEs were compared to a cohort of men not treated for prostate cancer. Results: Median follow-up was 4.3 years. At 8 years, the propensity weighted cumulative UAE incidence was highest after HDR+EBRT (28%) and lowest after LDR (17%; see Figure). The absolute excess risk over non-treated controls of a UAE at 8 years was 1.9%, 3.8%, 8.4% and 12.9% for the LDR, HDR, LDR + EBRT, and HDR + EBRT respectively. This translates into a number needed to harm of 53, 26, 12, and 8 persons. There is no statistical difference in severe UAE risk between HDR vs. LDR or between HDR+EBRT vs. LDR+EBRT. The additional risk for developing a UAE related to treatment for LDR, LDR+EBRT, and HDR+EBRT, was greatest within the 2 years following treatment, and continued to decline over time. For HDR monotherapy, the risk was greatest within the first 4 years, and then declined. The risk of developing a severe UAE matched the baseline risk of the control population for all treatments at 4 years following therapy. Conclusions: LDR and HDR brachytherapy are statistically indistinguishable for late severe urinary adverse events. However, combination radiotherapy (either HDR+EBRT or LDR+EBRT) increases the risk of severe UAEs compared to HDR alone or LDR alone. In the 8 years following brachytherapy treatment, the increased risk of urinary toxicity occurs almost exclusively within the 2 years following therapy, and then declines to a baseline hazard. The hypothesis that late urinary radiation toxicity accelerates over time is not supported by this study.

Pilot study of NKTR214 and nivolumab in patients with sarcomas.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11010-11010
Author(s):  
Sandra P. D'Angelo ◽  
Anthony Paul Conley ◽  
Ciara Marie Kelly ◽  
Mark Andrew Dickson ◽  
Mrinal M. Gounder ◽  
...  
Keyword(s):  
Pilot Study ◽  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Soft Part ◽  
Objective Response ◽  
Multiple Tumor ◽  
Pleomorphic Sarcoma ◽  
Treatment Naïve ◽  
Grade 3 ◽  
Tumor Types

11010 Background: Monotherapy checkpoint inhibitors have minimal efficacy in most patients with metastatic sarcoma. NKTR-214 is a CD122-preferential IL-2 pathway agonist that activates and expands natural killer and CD8+ T cells. Phase I/II data demonstrated the safety and efficacy of nivolumab plus NKTR-214 in multiple tumor types. A trial of NKTR-214 plus nivolumab was initiated in patients with selected sarcomas. Methods: This is a multi-center pilot study enrolling patients (pts) failing prior regimens within 9 cohorts: leiomyosarcoma (LMS), undifferentiated pleomorphic sarcoma (UPS), dedifferentiated liposarcoma (DDLPS), chondrosarcoma (CS), osteosarcoma (OS), angiosarcoma (AS), alveolar soft part sarcoma (ASPS), synovial sarcoma/small blue round cell and other. Pts received NKTR 0.006mg/kg with nivolumab 360 mg every 3 weeks. Primary endpoint was objective response rate (ORR), secondary endpoints were adverse events (AEs), progression-free, overall survival (PFS,OS) and clinical benefit rate (CBR.) Pre/on treatment biopsies performed on patients for correlative studies including PD-L1 expression and TIL characterization by immunohistochemistry, whole exome sequencing and RNAseq. Results: Enrollment completed with 10 patients in cohorts below. 50 pts enrolled (median age 58, range 14-80), 54% female. Median follow-up time is 13m. 50% of patients were refractory ≥3 lines of therapy. Grade 3/4 treatment related adverse events occurred in 26% of patients. 2% of patients stopped due to AEs. Median time to response was 3.6m. Responses seen in LMS, UPS, dedifferentiated CS; on-going in UPS/CS. Prolonged disease stability in DDLPS. 6 patients remain on treatment. Conclusions: Nivolumab plus NKTR-214 was safe and tolerable in heavily pre-treated and refractory sarcoma patients. Responses were protracted overtime; on-going in UPS and dedifferentiated CS. Prolonged disease stability seen in DDLPS in patients. All correlative analyses are in progress and will be presented. Enrollment continues with plans to add a treatment naïve cohort. Clinical trial information: NCT03282344. [Table: see text]

Rates of immunosuppressive treatment and hospitalization after checkpoint inhibitor therapy in melanoma and lung cancer patients with autoimmune diseases.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14140-e14140
Author(s):  
David Andrew Bender ◽  
Catherine Spina ◽  
Samuel P. Heilbroner ◽  
Eric Xanthopoulos ◽  
Tony J. C. Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Autoimmune Diseases ◽  
Cancer Patients ◽  
Checkpoint Inhibitors ◽  
Oral Prednisone ◽  
Immunosuppressive Treatment ◽  
Lung Cancer Patients ◽  
Pharmacy Claims ◽  
Increased Risk

e14140 Background: Immune checkpoint inhibitors (ICIs) are known to cause immune-related adverse events. Patients with autoimmune diseases (AID) were excluded from most ICI clinical trials due to the potentially high risk of adverse effects. Data on the safety of ICIs in patients with a diagnosis of AID is therefore limited. Methods: A retrospective cohort study was conducted using a de-identified large oncology health care and pharmacy claims database with data from March 2010 until April 2017. Patients analyzed had a diagnosis of either melanoma or lung cancer and were treated with either of the anti-PD-1 inhibitors nivolumab or pembrolizumab. We assessed whether patients with AID compared with no AID were more likely to require medical interventions within 180 days of ICI therapy. We determined the percentage of patients receiving oral prednisone, IV methylprednisolone, or were hospitalized, which may represent responses to ICI toxicity. Results: 16.7% (16/96) of patients with either melanoma or lung cancer and AID received oral prednisone treatment within 180 days of ICI treatment, while 8.3% (131/1573) of patients without AID received oral prednisone during the same period. 8.4% (16/190) of patients with AID received IV methylprednisolone compared to 3.6% (79/2190) of patients without AID. Among melanoma patients, 24.1% (13/54) of patients with AID were hospitalized following ICI treatment, compared to 5.8% (28/480) of patients without ICI. Among lung cancer patients, 38.2% (52/136) of patients with AID were hospitalized compared to 31.6% (541/1711) of patients without AID. All comparisons are significant at p < 0.05 except hospitalizations in lung cancer patients. Conclusions: Patients with AID were more likely to receive interventions after ICI treatment that may represent responses to immune-related adverse events, suggesting that patients with AID are at increased risk for toxicity when being treated with ICIs.

Incidence and prediction of checkpoint inhibitor immune-related nephrotoxicity.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 91-91
Author(s):  
Jonathan D Sorah ◽  
Tracy L. Rose ◽  
Roshni Radhakrishna ◽  
Vimal Derebail ◽  
Matthew I. Milowsky
Keyword(s):  
Autoimmune Disease ◽  
Adverse Events ◽  
Checkpoint Inhibitors ◽  
Kidney Injury ◽  
Retrospective Chart Review ◽  
Tumor Type ◽  
True Incidence ◽  
Platinum Based Chemotherapy ◽  
Increased Risk ◽  
Clinically Significant

91 Background: Immune checkpoint inhibitors (ICIs), through inhibition of self-tolerance, have the potential to cause immune-related adverse events that can affect any organ, including the kidneys. Our study aimed to better characterize the incidence of and predictive characteristics for immune-related nephrotoxicity. Methods: All patients at the University of North Carolina (UNC) who received ICIs between April 2014 and December 2018 for any malignancy were identified. Patients on dialysis or those who received concurrent platinum-based chemotherapy were excluded. Any patient who subsequently had a clinically significant acute kidney injury (AKI), defined as a doubling or more of baseline creatinine, was included for analysis. A retrospective chart review was performed to determine the cause of AKI. Any uncertain cases were reviewed by two nephrologists for expert consensus (R.R. and V.D.). Results: 1766 patients received an ICI during the study period. 123 (7%) patients had AKI within one year of the first ICI dose. 14 were due to immune-related nephrotoxicity (11% of patients with AKI and 0.8% of all ICI patients). Pre-existing autoimmune disease was more likely in patients with immune-related nephrotoxicity than in those with non-immune AKI (14% vs 3%, p = 0.04). Similarly, concurrent or prior other immune-related adverse events were more common in patients with immune-related AKI (57% vs 6%, p = 0.01). Patients with immune-related AKI were more likely to see a nephrologist (57% vs 23%, p = 0.007) and had a more profound increase in creatinine from baseline (median 2.6 vs 1.6, p = 0.02). Age, sex, urinalysis findings, and primary tumor type were not associated with increased risk. Conclusions: The true incidence of ICI related nephrotoxicity is difficult to ascertain due to the many confounders that contribute to AKI in this population. Severe immune-related nephrotoxicity is rare, but patients with preexisting autoimmune disease or history of immune-related adverse events are at increased risk.

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