Morphologic characteristics of cutaneous immune-related adverse events in patients receiving immune checkpoint inhibitors combined with other anticancer therapies: A multicenter retrospective study.
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ABSTRACT:
SUBMITTER: Asdourian MS
PROVIDER: S-EPMC10796161 | biostudies-literature | 2023 Feb
REPOSITORIES: biostudies-literature
Publications
Morphologic characteristics of cutaneous immune-related adverse events in patients receiving immune checkpoint inhibitors combined with other anticancer therapies: A multicenter retrospective study.
Asdourian Maria S MS Jacoby Ted V TV Shah Nishi N Thompson Leah L LL Otto Tracey T Semenov Yevgeniy R YR LeBoeuf Nicole R NR Reynolds Kerry L KL Dewan Anna K AK Chen Steven T ST
Journal of the American Academy of Dermatology 20220617 2
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Project description:Cutaneous immune-related adverse events are common in cancer patients receiving immunotherapies but seldom studied in a comprehensive way of collecting all cancer types with comparisons between different immune-oncology drugs and correlation to patient survival. In this retrospective cohort study, we recruited 468 cancer patients receiving immunotherapies in a tertiary referral center in Taiwan and try to determine real-world incidence of cutaneous immune-related adverse events and their associations with the survival rates. Among them, 128 patients (27.4%) had cutaneous immune-related adverse events, with maculopapular eruption (10.6%) and pruritus (10.1%) most frequently identified in the monotherapy group. The incidence of these cutaneous immune-related adverse events was highest in patients receiving pembrolizumab (34.1%, P < .0001). Concurrent usage of molecular-targeted therapy with immunotherapy was associated with a higher incidence (57.8%, P < .0001). The Kaplan-Meier plot and log-rank test showed that patients with any type of immune-related cutaneous adverse events had longer survival time than those without (P < .0001). In conclusion, having either type of cutaneous immune-related adverse event in cancer patients receiving immunotherapies was correlated with a longer overall survival. Prompt diagnosis and suitable treatment are important.
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Project description:BackgroundPatients who developed immune-related adverse events (irAEs) could benefit more from treatment with immune checkpoint inhibitors (ICIs) than those who did not develop irAEs. This study was designed to assess whether the occurrence of irAEs or their characteristics are correlated with survival in advanced patients treated with ICIs.MethodsThis retrospective cohort study enrolled a panel of cancer patients who received ICIs at a single institute. Kaplan‒Meier curves were generated to describe progression-free survival (PFS) and overall survival (OS) in patients with irAEs or specific irAE characteristics.ResultsA total of 238 patients were enrolled, 83 (34.9%) of whom developed at least one irAE. Overall, irAE development was associated with prolonged OS (not reached vs. 17.8 months, P < 0.001), PFS (8.7 vs. 4.8 months, P = 0.003), and an improved objective response rate (24.1% vs. 10.3%, P = 0.005). Furthermore, only skin or endocrine toxicities were associated with improved OS and PFS. On the basis of the results from organ-specific irAEs, the first development of skin or endocrine toxicities as protective irAEs rather than other irAEs was an independent indicator for predicting OS (P < 0.001) and PFS (P < 0.001). A protective irAE burden score based on organ-specific irAEs was further developed to show the significant protective effect of total irAEs on patient outcomes.ConclusionsNot all irAEs are associated with prolonged survival. The identification of organ-specific irAEs is useful for stratifying patients who actually respond to and benefit from ICIs across different cancer types.
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Project description:ImportanceSystemic steroids are commonly used to manage immune-related adverse events (irAEs), but it remains unclear whether they may undermine immune checkpoint inhibitor (ICI) therapy outcomes. Few studies have assessed the impact of steroid timing and its association with continuation or cessation of ICI therapy.ObjectiveTo characterize how systemic steroids and steroid timing for irAEs are associated with survival in patients receiving ICI therapy.Design, setting, and participantsThis multicenter retrospective cohort study encompassed veterans receiving ICI for cancer between January 1, 2010, and December 31, 2021. Data analysis was conducted September 8, 2023.ExposuresIdentifiable primary diagnosis of cancer. Patients were categorized into 3 cohorts: those receiving no steroids, systemic steroids for irAEs, and steroids for non-irAE-associated reasons. All eligible patients received 1 or more doses of an ICI (atezolizumab, avelumab, cemiplimab, durvalumab, ipilimumab, nivolumab, or pembrolizumab). Eligible patients in the steroid group received at least 1 dose (intravenous, intramuscular, or oral) of dexamethasone, hydrocortisone, methylprednisolone, prednisone, or prednisolone. Steroid use at baseline for palliation or infusion prophylaxis or delivered as a single dose was deemed to be non-irAE associated. All other patterns of steroid use were assumed to be for irAEs.Main outcomes and measuresThe primary outcome was overall survival, with a 5-year follow-up after ICI initiation. Kaplan-Meier survival analyses were performed with pairwise log-rank tests to determine significance. Risk was modeled with Cox proportional hazard regression.ResultsThe cohort consisted of 20 163 veterans receiving ICI therapy including 12 221 patients (mean [SD] age, 69.5 [8.0] years; 11 830 male patients [96.8%]; 9394 White patients [76.9%]) who received systemic steroids during ICI treatment and 7942 patients (mean [SD] age, 70.3 [8.5] years; 7747 male patients [97.5%]; 6085 White patients [76.6%]) who did not. Patients with an irAE diagnosis had significantly improved overall survival (OS) compared with those without (median [IQR] OS, 17.4 [6.6 to 48.5] months vs 10.5 [3.5 to 36.8] months; adjusted hazard ratio, 0.84; 95% CI, 0.81-0.84; P < .001). For patients with irAEs, systemic steroids for irAEs were associated with significantly improved survival compared with those who received steroids for non-irAE-related reasons or no steroid treatment (median [IQR] OS, 21.3 [9.3 to 58.2] months vs 13.6 [5.5 to 33.7] months vs 15.8 [4.9 to not reached] months; P <.001). However, among those who received steroids for irAEs, early steroid use (<2 months after ICI initiation) was associated with reduced relative survival benefit vs later steroid use, regardless of ICI continuation or cessation following steroid initiation (median [IQR] OS after ICI cessation 4.4 [1.9 to 19.5] months vs 16.0 [8.0 to 42.2] months; median [IQR] OS after ICI continuation, 16.0 [7.1 to not reached] months vs 29.2 [16.5 to 53.5] months; P <.001).Conclusions and relevanceThis study suggests that steroids for irAE management may not abrogate irAE-associated survival benefits. However, early steroid administration within 2 months of ICI initiation is associated with shorter survival despite continuation of ICI therapy.
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Project description:BackgroundDermatoses are common and potentially serious complications of programmed cell death receptor PD-1 immune checkpoint inhibitor (anti-PD-1 ICI) therapy. Understanding their incidence is necessary to support clinical awareness, diagnosis, and management.ObjectiveTo examine the incidence and odds of reported non-cancerous dermatoses in the setting of anti-PD-1 ICI therapy.MethodsCross-sectional study of anti-PD-1 (pembrolizumab or nivolumab) treated patients at a tertiary healthcare institution. Selected dermatologic events following immunotherapy were identified in the electronic medical record. Comparator arm were patients that developed these same dermatoses without receiving anti-PD-1 ICI therapy.ResultsThere were 13.7% (254/1857) patients that developed one of 28 dermatoses. Compared with the general population, patients treated with anti-PD-1 had a greater risk for development of mucositis (OR 65.7, 95% CI 35.0-123.3), xerostomia (OR 11.9, 95% CI 8.4-16.8), pruritus (11.3, 95% CI 8.9-14.3), and lichen planus/lichenoid dermatitis (OR 10.7, 95% CI 5.6-20.7).ConclusionsWe report the frequency of dermatoses encountered in the setting of ICI therapy, both common (pruritus, rash, vitiligo) and uncommon (scleroderma, urticaria).
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Project description:PurposeImmune-related cutaneous adverse events (ircAE) occur in ≥50% of patients treated with checkpoint inhibitors, but the underlying mechanisms for ircAEs are poorly understood.Experimental designPhenotyping/biomarker analyses were conducted in 200 patients on checkpoint inhibitors [139 with ircAEs and 61 without (control group)] to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip extracts, and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays.ResultsEight ircAE phenotypes were identified: pruritus (26%), maculopapular rash (MPR; 21%), eczema (19%), lichenoid (11%), urticaria (8%), psoriasiform (6%), vitiligo (5%), and bullous dermatitis (4%). All phenotypes showed skin lymphocyte and eosinophil infiltrates. Skin biopsy PCR revealed the highest increase in IFNγ mRNA in patients with lichenoid (P < 0.0001) and psoriasiform dermatitis (P < 0.01) as compared with patients without ircAEs, whereas the highest IL13 mRNA levels were detected in patients with eczema (P < 0.0001, compared with control). IL17A mRNA was selectively increased in psoriasiform (P < 0.001), lichenoid (P < 0.0001), bullous dermatitis (P < 0.05), and MPR (P < 0.001) compared with control. Distinct cytokine profiles were confirmed in skin tape strip and plasma. Analysis determined increased skin/plasma IL4 cytokine in pruritus, skin IL13 in eczema, plasma IL5 and IL31 in eczema and urticaria, and mixed-cytokine pathways in MPR. Broad inhibition via corticosteroids or type 2 cytokine-targeted inhibition resulted in clinical benefit in these ircAEs. In contrast, significant skin upregulation of type 1/type 17 pathways was found in psoriasiform, lichenoid, bullous dermatitis, and type 1 activation in vitiligo.ConclusionsDistinct immunologic ircAE endotypes suggest actionable targets for precision medicine-based interventions.
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Project description:Immune checkpoint inhibitors (ICIs) have been approved for monotherapy and combined therapy with chemotherapy and/or radiotherapy in China since 2018. The number of patients receiving ICIs has significantly increased in recent years, and the collection and analysis of this data are crucial for a comprehensive understanding of their clinical outcomes and adverse effects. The effects of ICIs may vary among different ethnic groups, and there is a lack of such data in the Chinese population. This study aimed to investigate the occurrence rate of various types of immune-related adverse events (irAEs) of ICIs in cancer survivors with different types of cancer and explore the associated risk factors. Demographic data, cancer type, dosage, Eastern Cooperative Oncology Group Performance Score (ECOG-PS), and details of irAEs were collected from 120 participants who underwent ICI treatment. Descriptive statistics were used to summarise the patient population characteristics, while t-tests and Chi-square tests assessed associations between variables. Multiple logistic regression evaluated the relationships between independent variables and the likelihood of experiencing irAEs. The results indicated that the occurrence of less severe G1 and G2 irAEs was 25%, while more severe G3 to G5 irAEs accounted for 5.8% of the total. Among the irAEs, skin toxicity had the highest incidence rate (14.2%), followed by gastrointestinal toxicity (6.7%), and endocrine toxicity had the lowest incidence rate of 2.5%. The multiple logistic regression model revealed that patients with ECOG-PS ≥ 2 are over five times more likely to experience irAEs compared to those with lower ECOG-PS (OR: 5.03, 95% CI: 1.05-24.17). Additionally, patients with cancer stage IV have 11.47 times the odds of experiencing irAEs (OR: 11.47, 95% CI: 1.05-24.17). In conclusion, a substantial proportion of patients receiving ICIs experienced irAEs. Patients with an ECOG-PS score of ≥ 2 and advanced cancer stage are at increased risk for these events, necessitating close monitoring by healthcare professionals. The identification of skin and gastrointestinal toxicities as the most common irAEs revealed the need for targeted education for the patients and their carers to recognise and manage these issues. Furthermore, our findings, in conjunction with existing literature, may guide future research on predictive modelling for high-risk patients receiving ICIs.
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