Racial differences in development of immune-related adverse events.

e15148 Background: Immune-related adverse events (irAEs) due to immune checkpoint inhibitors (ICIs) are caused by non-specific immune system activation and develop in 30-70% of patients. The goal of this study is to examine the association of race with the development of irAEs secondary to ICIs as autoimmune diseases generally exhibit racial differences. Methods: A retrospective chart review was done using University of Louisville pharmacy database. Patients with solid cancers who received ICIs between Jan 2016 to June 2019 were included. IrAEs were identified through the review of electronic medical records. Descriptive analysis evaluated the incidence and severity of irAEs. Multivariable logistic regression was used to calculate standardized incidence of irAEs among Whites and African Americans. Results: A total of 476 patients were included in this study. The mean age was 61 years, 57% were males and 89.7% were whites. A majority of patients had melanoma (50%). The remainder of the dataset included lung (33.4%), gastrointestinal (7.4%), head & neck (4.8%), breast (2.5%) and genitourinary (1.9%) cancers. ICIs included single agent anti-PD-1 (74.8%), single agent anti-PD-L1 (9.4%), combination anti-CTLA-4 with anti-PD-1 (7.1%). Some patients were also treated with > 1 ICI as subsequent therapy (8.6%). Overall, the rate of irAEs was 44.3% with 33.8% grade 1-2 and 12.4% grade 3-4 irAEs. There was no difference in development of any grade irAEs in Whites as compared to African Americans after adjusting for age, sex, cancer type and ICIs (44.3% vs 44.2%; OR: 0.99, 95% CI: 0.50 – 1.97; p = 0.99). There was also no difference in development of grade 3-4 irAEs in whites as compared to African Americans (12.8% vs 14.5%; OR: 1.16, 95% CI: 0.43 – 3.12; p = 0.75). Conclusions: In this study, we found no racial difference in the development of irAEs between Whites and African Americans. This is in contrast to general autoimmune diseases which exhibit racial differences with higher prevalence among African Americans compared to Whites. We will continue to accrue patients to this study as larger sample size is needed to confirm these findings.

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Management of immune-related adverse events: A single-center retrospective analysis in a real-world scenario.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15163 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15163-e15163

Author(s):

Donatella Iacono ◽

Maria Grazia Vitale ◽

Francesco Cortiula ◽

Marianna Macerelli ◽

Marika Cinausero ◽

...

Keyword(s):

Adverse Events ◽

Checkpoint Inhibitors ◽

Immunosuppressive Agents ◽

Management Strategies ◽

Immunosuppressive Treatment ◽

Second Line ◽

Cutaneous Toxicity ◽

Immune System Activation ◽

Grade 3 ◽

Ecog Ps

e15163 Background: Immune checkpoint inhibitors (ICI), anti CTLA-4 and anti PD-1/PD-L1 agents, have demonstrated an improvement in survival outcome in several malignancies. Therapy with ICI is characterized by immune-related adverse events (irAEs) as a result of exuberant immune system activation. Despite good tolerance for ICI, the potentially severe and life-threatening irAEs underscore the importance of investigating optimal management strategies. Methods: A retrospective series of 130 consecutive patients (pts) treated with ICI from Jan 2012 to Dec 2017 was analyzed. Adverse events with a potential immunological etiology were defined as irAEs and graded according to CTCAE v.4.0. The aim of the study was to evaluate irAEs management in an academic hospital center. Results: Pts with a diagnosis of NSCLC n = 64 (49%), melanoma n = 55 (42%), kidney n = 9 (7%) and others n = 2 (2%) were investigated. Baseline ECOG PS was ≤ 1 in 96% of the pts. ICI represented first line treatment for 27% pts, second line for 57% and third or further line for the remaining 16%. 18% were treated with ipilimumab and 82% with anti PD-1/PD-L1 agents (nivolumab 60%, pembrolizumab 21%, atezolizumab 1%). Overall, 50 (38% of pts) developed an irAE.42% of irAEs were grade 1, 38% grade 2, 14% grade 3 and 6% grade 4. The most frequent irAEs were endocrinopathies in 17 pts (34%), followed by cutaneous toxicity in 9 pts (18%) and colitis and diarrhea in 7 pts (14%). A total of 373 unscheduled accesses were observed, 89 (24%) of them were due to irAEs: 78 were unplanned consultations in the oncology department and 11 in the emergency department. irAEs led to hospitalization in 14 pts for 118 days, cumulatively. Grade ≥ 2 colitis was the most frequent irAE associated with hospitalization, it occurred in 4 pts (29%). Colitis and diarrhea required the longest hospitalization (range 4-31 days). 48% (24 pts) required immunosuppressive treatment. Systemic steroids were the most common immunosuppressive agents used. Only one patient received infliximab as second line immunosuppressive treatment after steroid failure. Totally, irAEs required 67 specialist consultancies and additional diagnostic examinations. 15 pts required ICI discontinuation because of irAEs. Conclusions: In our center prevalence and severity of irAEs were similar to literature data. Considered the complexity of irAEs management, multidisciplinary approach and a trained hospital network plays a key role for a more efficient diagnostic and treatment work-up in pts who received ICI therapy and experienced irAEs.

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Improved survival among patients with malignant pleural mesotheliomas who develop immune-related adverse events on immunotherapy.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8556 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8556-8556

Author(s):

Michael Offin ◽

Jacklynn V. Egger ◽

Caroline G. McCarthy ◽

Vasilisa Rudneva ◽

Jason Beattie ◽

...

Keyword(s):

Adverse Events ◽

Median Time ◽

Checkpoint Inhibitors ◽

Single Agent ◽

Progression Free Survival ◽

Clinicopathologic Characteristics ◽

Kaplan Meier ◽

Clinicopathologic Feature ◽

Thoracic Radiation ◽

Grade 3

8556 Background: While immune checkpoint inhibitors (ICI) are a standard option for patients with malignant pleural mesotheliomas (MPM), there is limited data on the rate of immune related adverse events (irAEs) and effects on clinical outcomes. Methods: 61 patients with MPM who received ICI between January 2016 and October 2020 were assessed and followed through November 2020. irAEs (CTCAE v5.0) were noted along with the time from ICI start to irAE onset. Patients were grouped into irAE ever versus never. Clinicopathologic characteristics, prior treatments, and investigator assessed clinical benefit rate (CBR; partial response [PR] + stable disease [SD]) were compared by Fisher’s Exact and Mann-Whitney Tests. Overall survival (OS) and investigator assessed progression free survival (PFS) from ICI start were compared using Kaplan Meier. In consented patients (n = 56), next generation sequencing (MSK-IMPACT) was performed with HLA genotyping analysis by POLYSOLVER software and alleles for the three major MHC class I (HLA-A, -B, -C) genes were obtained from whole exome recapture. Results: Most patients were male (72%), smokers (55%), > 70 years old (median 72, range 34-90), and had epithelioid histology (67%). No patients had baseline autoimmune disease. The median line of prior systemic therapies to ICI start was 2 (range 1-5). 17 patients (28%) developed an irAE on therapy including 7 (11%) with grade 3 to 5 events (pneumonitis, myositis, pancreatitis, nephritis, encephalitis and adrenal insufficiency). The median time from ICI start to irAE was 2.5 months (range 2 days – 5.8 months). There was no association with dual ICI (n = 6) vs single agent (n = 11) and sooner onset (2.1 vs 4.0 months; p = 0.10) nor higher grade (median grade 2 vs 3; p = 0.31) of irAEs. 1 patient developed grade 5 pneumonitis with onset 2 days after initial dose of dual-ICI. Comparing patients with irAEs to those without, there was no difference in distribution of epithelioid histology (n = 10 vs 31; p = 0.54), median age (71 vs 72 years old; p = 0.43), nor prior thoracic radiation (n = 5 vs 11; p = 0.75).There was no difference in HLA type nor the fraction of HLA alleles of individual genes amongst the groups. Patients who had an irAE were on ICI longer than those that did not (median time on ICI 5.4 vs 0.9 months, respectively; p = 0.02). OS was higher in patients with irAEs compared to those without (21.1 vs 4.7 months; p = 0.003) as was PFS (6.8 vs 1.7 months; p = 0.01). There was a significant increase in the CBR between those that had an irAE (65%; 5 PR, 6 SD) and those that did not (27%; 2 PR, 10 SD; p = 0.006). Conclusions: 28% of patients with MPM who received ICIs developed an irAE and onset tended to be early in the course of treatment. There was no clear predictive clinicopathologic feature that correlated with the occurrence of irAE. There was a significant increase in OS, PFS, and CBR in patients that had an irAE compared to those that did not.

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Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes

Cancers ◽

10.3390/cancers13102365 ◽

2021 ◽

Vol 13 (10) ◽

pp. 2365

Author(s):

Charline Lafayolle de la Bruyère ◽

Pierre-Jean Souquet ◽

Stéphane Dalle ◽

Pauline Corbaux ◽

Amélie Boespflug ◽

...

Keyword(s):

Adverse Events ◽

Checkpoint Inhibitors ◽

Single Agent ◽

Progression Free Survival ◽

Long Term Outcomes ◽

Term Survival ◽

Glucocorticoid Administration ◽

Grade 3 ◽

The Impact

It remains unclear whether immune-related adverse events (irAEs) and glucocorticoid use could impact long-term outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective unicentric study. The objectives were to assess the impact of grade ≥3 irAEs, glucocorticoid use and the interruption of immunotherapy on progression-free survival (PFS) and overall survival (OS). In this 828-patient cohort, the first occurrence of grade ≥3 irAEs had no significant impact on PFS or OS. Glucocorticoid administration for the irAEs was associated with a significantly shorter PFS (adjusted HR 3.0; p = 0.00040) and a trend toward shorter OS. ICI interruption was associated with a significantly shorter PFS (adjusted HR 3.5; p < 0.00043) and shorter OS (HR 4.5; p = 0.0027). Glucocorticoid administration and ICI interruption were correlated. In our population of patients treated with single agent ICI, grade ≥3 irAEs did not impact long-term outcomes. However, the need for glucocorticoids and the interruption of immunotherapy resulted in poorer long-term outcomes. The impact of grade ≥3 irAEs reported in other studies might then be explained by the management of the irAEs.

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Tivozanib combined with nivolumab: Phase Ib/II study in metastatic renal cell carcinoma (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.6_suppl.618 ◽

2018 ◽

Vol 36 (6_suppl) ◽

pp. 618-618 ◽

Cited By ~ 15

Author(s):

Bernard Escudier ◽

Philippe Barthelemy ◽

Alain Ravaud ◽

Sylvie Negrier ◽

Michael N. Needle ◽

...

Keyword(s):

Adverse Events ◽

Checkpoint Inhibitors ◽

Single Agent ◽

Elevated Serum ◽

Safety Data ◽

Growth Factor Receptor ◽

High Specificity ◽

Serum Lipase ◽

Phase Ib ◽

Grade 3

618 Background: Tivozanib is a VEGFR-TKI with high specificity and lower incidence of class effect adverse events. As combinations of vascular endothelial growth factor receptor tyrosine kinase inhibitiors (VEGFR-TKIs) and checkpoint inhibitors have proven to be toxic, alternatives with an improved AE profile are required. We present safety data from a phase Ib/II combination of tivozanib and nivolumab Methods: In this phase Ib/II study, tivozanib was administered orally at two dose levels, 1.0 mg and 1.5 mg, once daily for 21 days every 28 day cycle in combination with nivolumab 240 mg every 14 days intravenously. Results: Eighteen patients have been enrolled. Phase Ib is complete. Safety data is available for 13, 3 at 1.0 mg tivo; 10 at 1.5 mg tivo. The median age was 62; 11 patients were ECOG 0 and 5 ECOG 1; and there were 13 males. 16 had clear cell histology No patient in phase Ib experienced an DLT in cycle 1. Patients in phase II are receiving tivozanib at 1.5 mg. All patients experienced at least one AE. The most common adverse events were hypertension, asthenia, mucositis, diarrhea, hand foot syndrome, arthralgia, and pruritis. Five patients (38%) had grade 3-4 AEs. One patient had both elevated serum lipase and amylase and one patient had an SAE of symptomatic malignant hypertension complicated by a seizure. The other grade 3-4 AEs were pneumonitis, stomatitis, and elevated ALT. Conclusions: As expected from a VEGFR-TKI with high specificity and a preferable toxicity pattern as a single agent, the combination of tivozanib with nivolumab is safe and manageable at full dose of both drugs. Efficacy is pending. This data is based on limited exposure and should be interpreted with caution. Additional patients are being enrolled and treated. This begs the question if tivozanib could be added to a triple combination with ipilimumab and nivolumab. Clinical trial information: NCT03136627. [Table: see text]

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Comparative efficacy, safety, and tolerability of immune checkpoint inhibitors (ICIs) in cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e15151 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e15151-e15151

Author(s):

Laith Al-Showbaki ◽

Michelle Nadler ◽

Alexandra Desnoyers ◽

Fahad Almugbel ◽

David W. Cescon ◽

...

Keyword(s):

Adverse Events ◽

Urothelial Cancer ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Single Agent ◽

Similar Efficacy ◽

Microsoft Excel ◽

Serious Adverse Events ◽

Comparative Safety ◽

Grade 3

e15151 Background: Multiple ICIs have been approved, and in some diseases there is a choice of more than one ICI. The comparative safety, efficacy, and tolerability are not known. Here we report on a network meta-analysis comparing different ICIs targeting PD1 or PDL1. Methods: Randomized trials (RCTs) supporting the registration of a single agent anti-PD1 or anti-PDL1 inhibitors between 2015-2019 were identified. We extracted the hazard ratio (HR) for overall survival (OS) and calculated the odds ratio (OR) for commonly reported safety and tolerability outcomes. We then performed a network meta-analysis including only disease sites in which more than one ICI has been approved. Multiple pair-wise comparisons were then performed. When more than 2 comparisons were available for a pair of ICIs these were pooled into a single estimate. Analyses were performed in Microsoft Excel and RevMan 5.3. Results: Of 16 RCTs included, 10 in non-small-cell lung cancer, 2 in melanoma, 2 in head and neck squamous cell carcinoma and 2 in urothelial cancer. There was a total of 10673 patients in the analysis. Compared to pembrolizumab, efficacy was similar for nivolumab (HR 1.06, 95% CI 0.97-1.16) and for atezolizumab (HR 1.05, 95% CI 0.93-1.20). However, avelumab appeared inferior (HR 1.29, 95% CI 1.07-1.57). Pembrolizumab showed similar odds of serious adverse events (SAEs) as nivolumab (OR 1.12, 95% CI 0.56-2.27) and atezolizumab (OR 1.05, 95% CI 0.55-2.04). However, compared to nivolumab, atezolizumab was associated with more SAEs (OR 2.14, 95% CI 1.47-3.12). Avelumab had the lowest odds of grade 3-4 adverse events compared to pembrolizumab (OR 0.42, 95% CI 0.24-0.74), nivolumab (OR 0.38, 95% CI 0.24-0.62) and atezolizumab (OR 0.21, 95% CI 0.14-0.33). Atezolizumab was associated with more grade 3-4 adverse events than nivolumab (OR 1.84, 95% CI 1.37-2.47). The odds of treatment discontinuation without progression were similar between nivolumab and atezolizumab (OR 1.20, 95% CI 0.73-2.00), but higher with pembrolizumab compared to nivolumab (OR 1.35, 95% CI 0.83-2.17) and atezolizumab (OR 2.56, 95% CI 1.29-5.00). Pembrolizumab was associated with higher OR of immune related adverse events (IRAEs) compared to nivolumab (OR 2.12, 95% CI 1.49-3.03) and atezolizumab (OR 1.63, 95% CI 1.09-2.43), while the OR of IRAEs was almost similar between nivolumab and atezolizumab. Conclusions: Pembrolizumab, nivolumab, and atezolizumab have similar efficacy. Avelumab appears efficacious. Safety and tolerability seem better with avelumab, but worse with atezolizumab and pembrolizumab.

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The Price of Success: Immune-Related Adverse Events from Immunotherapy in Lung Cancer

Current Oncology ◽

10.3390/curroncol28060373 ◽

2021 ◽

Vol 28 (6) ◽

pp. 4392-4407

Author(s):

Courtney H. Coschi ◽

Rosalyn A. Juergens

Keyword(s):

Immune Response ◽

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Low Grade ◽

Cancer Type ◽

Immune System Activation ◽

Cancer Types ◽

System Activation

Cancer immunotherapy has the goal of enhancing a patient’s intrinsic immune processes in order to mount a successful immune response against tumor cells. Cancer cells actively employ tactics to evade, delay, alter, or attenuate the anti-tumor immune response. Immune checkpoint inhibitors (ICIs) modulate endogenous regulatory immune mechanisms to enhance immune system activation, and have become the mainstay of therapy in many cancer types. This activation occurs broadly and as a result, activation is supraphysiologic and relatively non-specific, which can lead to immune-related adverse events (irAEs), the frequency of which depends on the patient, the cancer type, and the specific ICI antibody. Careful assessment of patients for irAEs through history taking, physical exam, and routine laboratory assessments are key to identifying irAEs at early stages, when they can potentially be managed more easily and before progressing to higher grades or more serious effects. Generally, most patients with low grade irAEs are eligible for re-challenge with ICIs, and the use of corticosteroids to address an irAE is not associated with poorer patient outcomes. This paper reviews immune checkpoint inhibitors (ICIs) including their mechanisms of action, usage, associated irAEs, and their management.

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Abstract 3060: Racial Disparities in Early Institution of “Do Not Resuscitate” Orders Influence Survival in Acute Ischemic Strokes.

Stroke ◽

10.1161/str.43.suppl_1.a3060 ◽

2012 ◽

Vol 43 (suppl_1) ◽

Author(s):

Pratik Bhattacharya ◽

Ambooj Tiwari ◽

Sam Watson ◽

Scott Millis ◽

Seemant Chaturvedi ◽

...

Keyword(s):

Critical Care ◽

African American ◽

Ischemic Stroke ◽

African Americans ◽

Acute Ischemic Stroke ◽

Racial Differences ◽

Racial Disparity ◽

Retrospective Chart Review ◽

Do Not Resuscitate ◽

Dnr Orders

Background: The importance of early institution of “Do Not Resuscitate” (DNR) orders in determining outcomes from intracerebral hemorrhage is established. In the setting of acute ischemic stroke, African Americans tend to utilize critical care interventions more and palliative care options less than Caucasians. Recent epidemiological studies in acute ischemic stroke have shown a somewhat better survival for African Americans compared with Caucasians. Our hypothesis was that racial differences in early institution of DNR orders would influence mortality in acute ischemic stroke. Methods: a retrospective chart review was conducted on consecutive admissions for acute ischemic stroke across 10 hospitals in Michigan for the year 2006. Subjects with self reported race as African American or Caucasian were selected. Demographics, stroke risk factors, pre morbid status, DNR by day 2 of admission, stroke outcome and discharge destination were abstracted. Results: The study included 574 subjects (144 African American, 25.1%; 430 Caucasian, 74.9%). In-hospital mortality was significantly higher among Caucasians (8.6% vs. 1.4% amongst African Americans, p=0.003). More Caucasians had institution of DNR by day 2 than African Americans (22.5% vs. 4.3%, p<0.0001). When adjusted for racial differences in DNR by day 2 status, Caucasian race no longer predicted mortality. Caucasians were significantly older than African Americans (median age 76 vs. 63.5 years, p<0.0001); and age was a significant predictor of DNR by day 2 and mortality. In the adjusted analysis, however, age marginally influenced the racial disparity in mortality ( table ). Caucasians with coronary disease, atrial fibrillation, severe strokes and unable to walk prior to the stroke tend to be made DNR by day 2 more frequently. Only 27.1% of Caucasians with early DNR orders died in the hospital, whereas 20.8% were eventually discharged home. Conclusions: Early DNR orders result in a racial disparity in mortality from acute ischemic stroke. A substantial proportion of patients with early DNR orders eventually go home. Postponing the use of DNR orders may allow aggressive critical care interventions that may potentially mitigate the racial differences in mortality.

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Systematic Review and Network Meta-Analysis of Immune Checkpoint Inhibitors in Combination with Chemotherapy as a First-Line Therapy for Extensive-Stage Small Cell Carcinoma

Cancers ◽

10.3390/cancers12123629 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3629

Author(s):

Hsiao-Ling Chen ◽

Yu-Kang Tu ◽

Hsiu-Mei Chang ◽

Tai-Huang Lee ◽

Kuan-Li Wu ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Small Cell ◽

Randomized Controlled ◽

Extensive Stage ◽

Grade 3

Patients with extensive-stage small cell lung cancer (ED-SCLC) have a very short survival time even if they receive standard cytotoxic chemotherapy with etoposide and platinum (EP). Several randomized controlled trials have shown that patients with ED-SCLC who received a combination of EP plus immune checkpoint inhibitors (ICIs) had superior survival compared with those who received EP alone. We conducted a systematic review and network meta-analysis to provide a ranking of ICIs for our primary endpoints in terms of overall survival (OS), progression free survival (PFS), and objective response rate (ORR), as well as our secondary endpoint in terms of adverse events. The fractional polynomial model was used to evaluate the adjusted hazard ratios for the survival indicators (OS and PFS). Treatment rank was estimated using the surface under the cumulative ranking curve (SUCRA), as well as the probability of being best (Prbest) reference. EP plus nivolumab, atezolizumab or durvalumab had significant benefits compared with EP alone in terms of OS (Hazard Ratio HR = 0.67, 95% Confidence Interval CI = 0.46–0.98 for nivolumab, HR = 0.70, 95% CI = 0.54–0.91 for atezolizumab, HR = 0.73, 95% CI = 0.59–0.90 for durvalumab) but no significant differences were observed for pembrolizumab or ipilimumab. The probability of nivolumab being ranked first among all treatment arms was highest (SCURA = 78.7%, Prbest = 46.7%). All EP plus ICI combinations had a longer PFS compared with EP alone (HR = 0.65, 95% CI = 0.46–0.92 for nivolumab, HR = 0.77, 95% CI = 0.61–0.96 for atezolizumab, HR = 0.78, 95% CI = 0.65–0.94 for durvalumab, HR = 0.75, 95% CI = 0.61–0.92 for pembrolizumab), and nivolumab was ranked first in terms of PFS (SCURA = 85.0%, Prbest = 66.8%). In addition, nivolumab had the highest probability of grade 3–4 adverse events (SUCRA = 84.8%) in our study. We found that nivolumab had the best PFS and OS in all combinations of ICIs and EP, but nivolumab also had the highest probability of grade 3–4 adverse events in our network meta-analysis. Further head-to head large-scale phase III randomized controlled studies are needed to verify our conclusions.

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Immune-related adverse events associated with immune checkpoint inhibitors in patients with cancer

Tumori Journal ◽

10.1177/0300891620953468 ◽

2020 ◽

pp. 030089162095346

Author(s):

Nilay Sengul Samanci ◽

Duygu Ilke Cikman ◽

Kerem Oruc ◽

Sahin Bedir ◽

Emir Çelik ◽

...

Keyword(s):

Adverse Events ◽

Health Care Providers ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Early Recognition ◽

Care Providers ◽

Patients With Cancer ◽

Combination Treatments ◽

Grade 3

Introduction: With the widespread use of immune checkpoint inhibitors (ICIs), we are facing challenges in the management of immune-related adverse events (irAEs). We aimed to characterize the spectrum of toxicity, management, and outcomes for irAEs. Methods: Patients who were treated with at least one ICI in clinical trials, expanded access programs, or routine clinical practice were included. Clinical and laboratory parameters were collected retrospectively to determine the incidence of irAEs, methods of management, and treatment outcomes. Results: A total of 255 patients were screened retrospectively. Of these, 71 (27.8%) patients developed irAEs. More than 2 different types of irAEs were detected in 16 (6.2%) out of 255 patients. A total of 3177 doses were given to 255 patients. In 93 (2.9%) of the 3177 doses, 1 episode of irAEs was experienced. A total of 22 out of 93 (23.7%) episodes were reported as grade 1, 49 (52.7%) as grade 2, 19 (20.4%) as grade 3, and 3 (3.2%) as grade 4. The most frequently seen irAEs were pneumonitis, hepatitis, and hypothyroidism. With regard to treatment, 39 out of 93 episodes (42%) of any grade irAEs occurred after anti–programmed cell death-1 therapy, 47 (50.5%) occurred following administration of anti–programmed death-ligand 1, and 7 (7.5%) occurred after combination treatments. Conclusion: With the increased use of immunotherapeutic agents, increased awareness and early recognition are required for effective management of irAEs. Our experience as a single institution might be of use for health care providers in oncology.

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Comparative risk of serious and fatal treatment-related adverse events caused by 19 immune checkpoint inhibitors used in cancer treatment: a network meta-analysis

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920940927 ◽

2020 ◽

Vol 12 ◽

pp. 175883592094092 ◽

Cited By ~ 1

Author(s):

Tingting Liu ◽

Bo Jin ◽

Jun Chen ◽

Hui Wang ◽

Shuiyu Lin ◽

...

Keyword(s):

Adverse Events ◽

Cancer Treatment ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

Meta Analysis ◽

Combinatorial Therapy ◽

Grade 5 ◽

Comparative Risk ◽

Grade 3

Background: This network meta-analysis assessed the comparative risk of grade 3–5 and grade 5 treatment-related adverse events (TRAEs) for immune checkpoint inhibitors (ICIs), either alone or in combination with other modalities, for cancer treatment. Methods: PubMed, Embase, Cochrane Library, Web of Science, and recent predominant oncology congresses were searched for relevant phase II and phase III randomized controlled trials (RCTs). As outcomes, grade 3–5, and grade 5 TRAE outcomes were reported as odds ratios and 95% confidence intervals. Results: In 67 RCTs involving 36,422 patients and 19 ICIs, the incidence of grade 3–5 and grade 5 TRAEs was 17.9% and 0.8% with ICI monotherapy and 46.3% and 1.4%, respectively, with combinatorial therapy. Pneumonitis was the most common cause of grade 5 TRAEs following either monotherapy (16.3%) or combinatorial therapy (11.4%). Regarding grade 3–5 TRAEs, atezolizumab + chemotherapy (CT) and antiangiogenic therapy (AT) (atezolizumab + CAT), pembrolizumab + CT, ipilimumab + CT, and atezolizumab + CT were more toxic than any ICI monotherapy, pembrolizumab or nivolumab + radiotherapy (RT), and ICIs dual therapy (durvalumab + tremelimumab and nivolumab + ipilimumab). Tremelimumab, ipilimumab, durvalumab, and pembrolizumab were, however, associated with higher grade 5 TRAEs than combinatorial treatments. Atezolizumab + CAT was the most toxic and nivolumab + RT was the least toxic of combinatorial treatments; among monotherapies, tremelimumab and avelumab were the most and least toxic, respectively. The toxicity ranking changed with type of grade 3–5 TRAEs. Conclusions: Compared with combinatorial therapy, ICI monotherapy caused lower grade 3–5 TRAEs, but some monotherapies resulted in a higher incidence of fatal TRAEs. Atezolizumab + CAT and nivolumab + RT were the most and least toxic of combinatorial treatments, respectively, and tremelimumab and avelumab were the most and least toxic of the monotherapies, respectively.

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