Correlation of immune-related adverse events and response from immune checkpoint inhibitors in patients with advanced non-small cell lung cancer.
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ABSTRACT:
SUBMITTER: Sung M
PROVIDER: S-EPMC7330321 | biostudies-literature | 2020 May
REPOSITORIES: biostudies-literature
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Correlation of immune-related adverse events and response from immune checkpoint inhibitors in patients with advanced non-small cell lung cancer.
Sung Mike M Zer Alona A Walia Preet P Khoja Leila L Maganti Manjula M Labbe Catherine C Shepherd Frances A FA Bradbury Penelope A PA Liu Geoffrey G Leighl Natasha B NB
Journal of thoracic disease 20200501 5
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Project description:Immune checkpoint inhibitors (ICIs) emerged as the preferred therapy in advanced lung cancer, understanding the treatment- and immune-related adverse events of these drugs is of great significance for clinical practice. PubMed, Embase, Cochrane library and major conference proceedings were systematically searched for all randomized controlled trials (RCTs) in lung cancer using PD-1/PD-L1/CTLA-4 inhibitors. The outcomes included treatment-related adverse events (TRAEs) and several organ specific immune-related adverse events (IRAEs). 24 RCTs involving 14,256 patients were included. There was a significant difference for ICI therapy in the incidence of any grade of TRAEs (RR: 0.90; 95%CI: 0.84-0.95; P=0.001) and a lower frequency of grade 3-5 of TRAEs (RR: 0.65; 95%CI: 0.51-0.82; P<0.001). Patients treated with ICI therapy in non-small-cell lung cancer (NSCLC) were less reported TRAEs than in small cell lung cancer (SCLC). A lower risk of TRAEs was favored by anti-PD-1 inhibitors over anti-PD-L1 antibodies and anti-CTLA-4 drugs. The most common organ specific IRAE was hypothyroidism that occurred 8.7%. The incidence of pneumonitis and hepatitis reached 4.5% and 4.0% respectively. Compared with patients treated in control arms, those treated with ICI drugs were at higher risk for each organ specific adverse event including colitis, hepatitis, pneumonitis, hypothyroidism and hypophysitis. ICI therapy was safer than chemotherapy, especially ICI monotherapy such as anti-PD-1 antibodies in NSCLC. Compared with standard treatments, ICI drugs increased the risk of organ-specific IRAEs, although the overall incidence remained low.
| S-EPMC7953488 | biostudies-literature
Project description:BackgroundAlthough predictive value of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) have been suggested by several studies, their assessments were insufficient because patients were categorized only by the occurrence of irAEs. It has not been elucidated whether irAEs also play a significant role even in responders.Materials and methodsBetween December 2015 and September 2018, 106 patients with advanced non-small cell lung cancer treated with ICIs were enrolled in our prospective biomarker study. Twenty-three of these were responders, defined as those with complete or partial response. We investigated the proportion of irAEs among overall and responders. For responders, progression-free survival (PFS) and overall survival of ICIs were compared between those with and without irAEs. As an exploratory analysis, we measured 41 proteins from peripheral blood before and after ICI treatment.ResultsThe proportion of irAEs was significantly higher in responders than nonresponders (65.2% vs. 19.3%, p < .01). Among responders, clinical characteristics did not differ regardless of the occurrence of irAEs. However, there was a significant difference in PFS among responders (irAE group 19.1 months vs. non-irAE group 5.6 months; hazard ratio: 0.30 [95% confidence interval: 0.10-0.85]; p = .02). Of 41 protein analyses, fibroblast growth factor-2 at baseline and monocyte chemoattractant protein fold change showed significant differences between them (p < .04).ConclusionAlthough this is a small sample-sized study, irAE might be a predictive factor of durable efficacy, even in patients who responded to ICIs. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI.Implications for practiceAlthough the predictive value of immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) has been suggested by several studies, it has not been elucidated whether irAEs also play a significant role even in responders. This study showed that more than 60% of responders had irAEs. It demonstrated the strong correlation between irAEs and efficacy even in responders. Investigation into the significance of irAEs in responders will contribute to the establishment of optimal administration of ICI.
| S-EPMC7160399 | biostudies-literature
Project description:Cancer immunotherapies have changed the landscape of cancer treatment during the past few decades. Among them, immune checkpoint inhibitors, which target PD-1, PD-L1 and CTLA-4, are increasingly used for certain cancers; however, this increased use has resulted in increased reports of immune-related adverse events (irAEs). These irAEs are unique and are different to those of traditional cancer therapies, and typically have a delayed onset and prolonged duration. IrAEs can involve any organ or system. These effects are frequently low grade and are treatable and reversible; however, some adverse effects can be severe and lead to permanent disorders. Management is primarily based on corticosteroids and other immunomodulatory agents, which should be prescribed carefully to reduce the potential of short-term and long-term complications. Thoughtful management of irAEs is important in optimizing quality of life and long-term outcomes.
| S-EPMC9728094 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) are novel immunotherapy-based drugs that have become increasingly popular in the treatment of lung cancer. Researchers have recognized ocular immune-related adverse events (irAEs) secondary to ICIs because of their vision-threatening characteristics. However, they are incompletely characterized and no studies have reported the ICI-related ocular irAEs in lung cancer. Therefore, we aimed to comprehensively illustrate the clinical characteristics, contributory factors, diagnosis, and management of ICI-related ocular irAEs in lung cancer, based on previously reported 79 patients. Ophthalmoplegia (40.51%), uveitis (20.25%), and dry eye (17.72%) were the most common ICI-related ocular irAEs in lung cancer. Ptosis was the most common (36.71%) and the highest mortality (23.33%) of ophthalmoplegia. Patients in Asia and patients who underwent combination therapy with programmed cell death-1 and cytotoxic T-lymphocyte-associated antigen 4 inhibitors demonstrated significantly higher frequency of ophthalmoplegia than other ocular irAEs. Most ICI-related ophthalmoplegia and uveitis in lung cancer were observed in the first 10 weeks following the initiation of ICIs. Furthermore, the onset time of dry eye and other ocular irAEs was much longer. In addition, 92.31% of the patients with ocular irAEs other than ophthalmoplegia could be remised. In conclusion, ocular irAEs secondary to ICIs in lung cancer are non-negligible, particularly ophthalmoplegia. Ethnicity and the type of ICIs play important roles in the distribution of ocular irAEs. ICI-related ophthalmoplegia in lung cancer presented with early onset and worse prognosis features, thus necessitating further attention.
| S-EPMC8421677 | biostudies-literature
Project description:ImportanceThe spectrum of individual immune-related adverse events (irAEs) from anti-programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) immune checkpoint inhibitors (ICIs) has been reported widely, and their development is associated with improved patient survival across tumor types. The spectrum and impact on survival for patients with non-small cell lung cancer (NSCLC) who develop multisystem irAEs from ICIs, has not been described.ObjectiveTo characterize multisystem irAEs, their association with survival, and risk factors for multisystem irAE development.Design, setting, and participantsThis retrospective cohort study carried out in 5 academic institutions worldwide included 623 patients with stage III/IV NSCLC, treated with anti-PD-(L)1 ICIs alone or in combination with another anticancer agent between January 2007 and January 2019.ExposuresAnti-PD-(L)1 monotherapy or combinations.Main outcomes and measuresMultisystem irAEs were characterized by combinations of individual irAEs or organ system involved, separated by ICI-monotherapy or combinations. Median progression-free (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method. Differences in PFS and OS between irAE groups were assessed by multivariable models. Risk for multisystem irAE was estimated as odds ratios by multivariable logistic regression.ResultsThe 623 patients included in the study were mostly men (60%, n = 375) and White (77%, n = 480). The median (range) age was 66 (58-73) years, and 148 patients (24%) developed a single irAE, whereas 58 (9.3%) developed multisystem irAEs. The most common multisystem irAE patterns in patients receiving anti-PD-(L)1 monotherapy were pneumonitis thyroiditis (n = 7, 14%), hepatitis thyroiditis (n = 5, 10%), dermatitis pneumonitis (n = 5, 10%), and dermatitis thyroiditis (n = 4, 8%). Favorable Eastern Cooperative Oncology Group (ECOG) performance status (PS) (ECOG PS = 0/1 vs 2; adjusted odds ratio [aOR], 0.27; 95% CI, 0.08-0.94; P = .04) and longer ICI duration (aOR, 1.02; 95% CI, 1.01-1.03; P < .001) were independent risk factors for development of multisystem irAEs. Patients with 1 irAE and multisystem irAEs demonstrated incrementally improved OS (adjusted hazard ratios [aHRs], 0.86; 95% CI, 0.66-1.12; P = .26; and aHR, 0.57; 95% CI, 0.38-0.85; P = . 005, respectively) and PFS (aHR, 0.68; 95% CI, 0.55-0.85; P = .001; and aHR, 0.39; 95% CI, 0.28-0.55; P < .001, respectively) vs patients with no irAEs, in multivariable models adjusting for ICI duration.Conclusions and relevanceIn this multicenter cohort study, development of multisystem irAEs was associated with improved survival in patients with advanced NSCLC treated with ICIs.
| S-EPMC7596677 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) therapy has revolutionized the treatment patterns of non-small cell lung cancer (NSCLC). However, patients treated with ICIs may experience immune-related adverse events (irAEs). Markers that could predict the onset of irAEs are still unclear. Here, we report the possible correlation of baseline peripheral lymphocytes with irAEs and clinical outcomes in advanced NSCLC patients receiving ICIs. A total of 109 advanced NSCLC patients treated with ICIs from April 2017 to January 2021 were analyzed retrospectively. Logistic and Cox regression analyses was applied to evaluate independent risk factors for irAEs, progression-free survival (PFS), and overall survival (OS). Among these patients, 55 (50.5%) patients experienced irAEs. The level of CD8+ T lymphocytes at baseline was the independent risk factor for the onset of irAEs (p = 0.008). A higher level of CD8+ T lymphocytes was associated with longer PFS (11.0 months vs. 3.0 months, p < 0.001) and OS (27.9 months vs. 11.7 months, p = 0.014). Furthermore, patients who had higher baseline CD8+ T lymphocytes and experienced irAEs had a longer PFS (18.4 months vs. 2.2 months, p < 0.001) and OS (32.8 months vs. 9.0 months, p = 0.001) than those who had lower CD8+ T lymphocytes and no irAEs. Our study highlights the value of baseline peripheral CD8+ T lymphocytes as a predictive factor for irAEs in advanced NSCLC patients receiving ICIs. In addition, patients who have higher baseline CD8+ T lymphocytes and experience irAEs would have a superior PFS and OS.
| S-EPMC9331848 | biostudies-literature
Project description:Objective: This network meta-analysis will provide a complete toxicity profile, toxicity profile, and safety ranking of immune checkpoint inhibitors (ICIs) for treatment of advanced non-small cell lung cancer (NSCLC). Methods: We found 12 phase II or III randomized clinical trials (RCTs) including 8,453 patients with NSCLC by searching Pubmed, Embase, and ClinicalTrials.gov. Risk ratios (RRs) and 95% confidence interval (CI) were used to compare the rate of immune-related adverse events (irAEs) for different ICIs-based treatments using pairwise and network meta-analysis with random effects. Results: For dermatologic irAEs, the corresponding ranking of incidences of the seven groups from high to low was: nivolumab + ipilimumab (97.4%), pembrolizumab (80.1%), nivolumab (67.1%), pembrolizumab + platinum (43.3%), atezolizumab + platinum (39.9%), durvalumab (17.5%), platinum-based chemotherapy (4.7%). For colitis, the corresponding ranking of incidences of the six groups from high to low was: atezolizumab + platinum (77.1%), nivolumab (67.3%), pembrolizumab (60.5%), durvalumab (45.2%), pembrolizumab + platinum (41.4%), platinum-based chemotherapy (8.5%). For endocrine irAEs, the corresponding ranking of incidences of the seven groups from high to low was: nivolumab + ipilimumab (79.1%), durvalumab (69.1%), pembrolizumab (61.9%), atezolizumab + platinum (60.4%),nivolumab (45.7%), pembrolizumab + platinum (33.5%), platinum-based chemotherapy (0.3%). For pneumonitis, the corresponding ranking of incidences of the seven groups from high to low was: pembrolizumab (99.3%), pembrolizumab + platinum (65.1%), durvalumab (62.2%), atezolizumab + platinum (56%), nivolumab (35.9%), platinum-based chemotherapy (18.1%),atezolizumab (13.3%). For hepatitis, the corresponding ranking of incidences of the six groups from high to low was: pembrolizumab (71.2%), pembrolizumab + platinum (64.3%), durvalumab (56.4%), atezolizumab + platinum (53.8%), nivolumab (44.5%), platinum-based chemotherapy (9.8%). Conlusion: In addition to platinum-based chemotherapy, durvalumab for dermatologic and liver irAEs, pembrolizumab for gastrointestinal irAEs, pembrolizumab + platinum for endocrine irAEs, and atezolizumab for pneumonitis may be associated with lower rates of irAEs than other immune-based regimens. Nivolumab + ipilimumab for dermatologic and endocrine irAEs, atezolizumab + platinum for colitis, and pembrolizumab for pneumonitis and hepatitis may be associated with higher rates of irAEs.
| S-EPMC8574003 | biostudies-literature
Project description:Immune checkpoint inhibitors (ICIs) have revolutionized treatment landscape among non-small cell lung cancer (NSCLC) patients in first- and second-line setting, and may become soon new treatment options in other thoracic malignancies such as small cell lung cancer (SCLC) or mesothelioma. The use of these drugs has indubitably changed the toxicity profile the oncologists are familiar with, and new spectra of immune-related adverse events are being reported with the widespread use of immunotherapies in solid tumors. Clinical management and understanding of immune-related adverse events is new and complex but expertise is still limited. In this review, we are summarizing the incidence and management of main side effects related to ICIs focusing on NSCLC patients.
| S-EPMC5994490 | biostudies-literature
Project description:BackgroundImmune-related adverse events (irAEs) caused by immune checkpoint inhibitors (ICIs) were associated with clinical benefit in cancer patients of melanoma, a lung cancer. In the present study, we investigated the correlation between irAE and ICI efficacy in hepatocellular carcinoma (HCC) patients.MethodsWe divided the HCC patients who received the anti-PD-1 antibody into two groups as irAE group and non-irAE group according to the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. The treatment efficacy of ICIs was evaluated with objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS).ResultOf the 65 HCC patients who received the anti-PD-1 antibody (monotherapy or combined with targeted medicine), median PFS in the irAE group was superior to that in the non-irAE group (302 days vs. 148 days, p = 0.004). Median OS in the irAE group was also better than that in the non-irAE group (374 days vs. 279 days, p = 0.038). Although the statistical difference for DCR in the irAE group and non-irAE group was not reached, the DCR of the irAE displayed a trend better than that of the non-irAE group (41.20% vs. 20.80%, p = 0.118). Multivariate analysis also demonstrated that the non-irAE group (HR = 6.410, 95% CI: 1.404 to 29.275) was associated independently with the poor prognosis.ConclusionsDevelopment of irAEs was associated with clinical benefit for HCC patients who were treated with immune checkpoint inhibitors; irAE, particularly low-grade irAE, was a predictable marker for better ICI treatment efficiency in HCC patients.
| S-EPMC8691363 | biostudies-literature
Project description:Small cell lung cancer (SCLC) is a malignant solid tumor. In recent years, although immune check point inhibitors (ICIs) have achieved important advances in the treatment of SCLC, immune-related adverse events (irAEs) have occurred at the same time during the therapeutic period. Some irAEs lead to dose reduction or treatment rejection. The immune microenvironment of SCLC is complicated, therefore, understanding irAEs associated with ICIs is of great importance and necessity for the clinical management of SCLC. However, the lack of comprehensive understanding of irAEs in patients with SCLC remains remarkable. This review aims to provide an up-to-date overview of ICIs and their associated irAEs in patients with SCLC based on present clinical data.
| S-EPMC8016392 | biostudies-literature