scholarly journals Immune-related adverse events: a retrospective look into the future of oncology in the intensive care unit

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Adrien Joseph ◽  
Audrey Simonaggio ◽  
Annabelle Stoclin ◽  
Antoine Vieillard-Baron ◽  
Guillaume Geri ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Adverse Events ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Primary Tumors ◽  
Icu Admission ◽  
Paris Area

Abstract Background Immune checkpoint inhibitors have reshaped the standard of care in oncology. However, they have been associated with potentially life-threatening immune-related adverse events. With the growing indications of immune checkpoint inhibitors and their position as a pillar of cancer treatment, intensive care physicians will be increasingly confronted with their side effects. The outcome of patients with severe immune-related adverse events in the intensive care unit remains unknown. This retrospective multicentric study aims to describe the characteristics of patients admitted to the intensive care units of 4 academic hospitals in Paris area while receiving immune checkpoint inhibitor treatment between January 2013 and October 2019. Results Over the study period, 112 cancer patients who received immune checkpoint inhibitors were admitted to the intensive care unit within 60 days after the last dose. ICU admission was related to immune-related adverse events (n = 29, 26%), other intercurrent events (n = 39, 35%), or complications related to tumor progression (n = 44, 39%). Immune-related adverse events were pneumonitis (n = 8), colitis (n = 4), myocarditis (n = 3), metabolic disorders related to diabetes (n = 3), hypophysitis (n = 2), nephritis (n = 2), meningitis or encephalitis (n = 2), hepatitis (n = 2), anaphylaxis (n = 2) and pericarditis (n = 1). Primary tumors were mostly melanomas (n = 14, 48%), non-small-cell lung cancers (n = 7, 24%), and urothelial carcinomas (n = 5, 17%). Diagnosis of melanoma and a neutrophil/lymphocyte ratio < 10 were associated with immune-related diagnosis versus other reasons for ICU admission. During their ICU stay, immune-related adverse events patients needed vasopressors (n = 7), mechanical ventilation (n = 6), and extra-corporeal membrane oxygenation (n = 2). One-year survival was significantly higher for patients admitted for irAE compared to patients admitted for other reasons (p = 0.004). Conclusions Admission to the intensive care unit related to immune-related adverse event was associated with better outcome in cancer patients treated with immune checkpoint inhibitors. Our results support the admission for an intensive care unit trial for patients with suspected immune-related adverse events.

scholarly journals Questionnaire-based detection of immune-related adverse events in cancer patients treated with PD-1/PD-L1 immune checkpoint inhibitors

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Luisa Maria Griewing ◽  
Claudia Schweizer ◽  
Philipp Schubert ◽  
Sandra Rutzner ◽  
Markus Eckstein ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Weight Change ◽  
Immune Checkpoint ◽  
Detection Rate ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Patient Questionnaire ◽  
Organ Specific ◽  
Tumor Entities

Abstract Background Immune checkpoint inhibitors (ICI) have become standard treatment in different tumor entities. However, safe treatment with ICI targeting the PD-1/PD-L1 axis requires early detection of immune-related adverse events (irAE). There exist different questionnaires of drug manufacturers for the detection of irAE that have not been validated so far. Methods The prospective non-interventional ST-ICI trial studied treatment with PD-1/PD-L1 ICI alone or combined with radiotherapy. In the current analysis, the detection rate of self-reported irAE with a patient questionnaire containing 41 different questions was compared to clinician-reported irAE. Results Between April 2017 and August 2019, a total of 104 patients were prospectively enrolled. NSCLC (44%) and HNSCC (42%) were the most frequent tumor entities. A total of 784 questionnaires were collected. A total of 29 irAE were reported by clinicians. The most frequent irAE was hypothyroidism (9%), followed by skin reactions (5%), hepatitis (4%), diarrhea (3%), and pneumonitis (3%). Questions that became significantly more often positive at time points of clinician-reported irAE were “weight change”, “difficulty to grip things”, “bloody or mucous stool” and “insomnia”. Self-reported organ-specific questions detected at least 50% of clinician-reported irAE of gastrointestinal, lung, endocrine, and skin irAE. It was not possible to detect hepatic irAE with the questionnaire. Conclusion Questionnaires can help to detect gastrointestinal, lung, endocrine, or skin irAE, but not hepatic irAE. Questions on “weight change” and “insomnia” may help to increase the detection rate of irAE, besides organ-specific questions. These results are a valuable contribution to the future development of a specific and practicable questionnaire for early self-reported detection of irAE during ICI therapy in cancer patients. Trial registration ClinicalTrials.gov, NCT03453892. Registered on 05 March 2018.

scholarly journals Association between Body Mass Index and Immune-Related Adverse Events (irAEs) among Advanced-Stage Cancer Patients Receiving Immune Checkpoint Inhibitors: A Pan-Cancer Analysis

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6109
Author(s):  
Dongyu Zhang ◽  
Neil J. Shah ◽  
Michael Cook ◽  
Matthew Blackburn ◽  
Michael T. Serzan ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Logistic Regression ◽  
Adverse Events ◽  
Cancer Patients ◽  
Body Mass ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Multivariable Logistic Regression Model ◽  
Multivariable Logistic Regression

Evidence regarding the association between body mass index (BMI) and immune-related adverse events (irAEs) among cancer patients receiving immune checkpoint inhibitors (ICIs) is limited. Here, we use cross-sectional hospital-based data to explore their relationship. Pre-treatment BMI was treated as an ordinal variable (<25, 25 to ≤30, ≥30 kg/m2). The outcome of interest was irAEs after ICI initiation. A multivariable logistic regression model estimated the adjusted odds ratio (aOR) and 95% confidence interval (CI) of BMI. A total of 684 patients with stage III or IV cancer were included in the study (lung: 269, melanoma: 204, other: 211). The mean age at the first dose of ICI was 64.1 years (SD = 13.5), 394 patients (57.6%) were male, and over one-third (N = 260, 38.0%) were non-White. Overall, 52.9% of patients had BMI ≥ 25 kg/m2 (25 to ≤30: 217, ≥30: 145) and 288 (42.1%) had irAEs after ICI treatment. Patients with higher BMI tended to have a higher rate of irAEs (<25: 35.7%, 25 to ≤30: 47.0%, ≥30: 49.0%). The multivariable logistic regression yielded consistent results (BMI ≥ 30 vs. BMI < 25: aOR = 1.47, 95% CI = 0.96–2.23; 25 ≤ BMI < 30 vs. BMI < 25: aOR = 1.46, 95% CI = 1.02–2.11, p-trend = 0.04). In conclusion, among patients with advanced cancer receiving ICIs, the rate of irAEs appears to be higher among those with higher BMI.

scholarly journals An Evaluation of the Use of Corticosteroids for the Management of Immune-Mediated Adverse Events in Cancer Patients Treated With Immune Checkpoint Inhibitors

2021 ◽  
Vol 12 (2) ◽  
Author(s):  
Adrian Tsui, PharmD ◽  
Linday Edmondson, PharmD, BCOP ◽  
Justin Julius, PharmD
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Retrospective Chart Review ◽  
Prescribing Practices ◽  
Immune Mediated ◽  
Number Of Patients ◽  
Secondary Endpoints

Immune checkpoint inhibitors (ICIs) have gained prominence for the treatment of a variety of malignancies. However, they are associated with the development of immune-mediated adverse events (IMAEs). Appropriate management of IMAEs and subsequent rechallenging of patients with ICI therapy remains an important area of research. The primary endpoint of this study was to evaluate the efficacy of current prescribing practices and adherence to guideline recommendations for IMAE management. The incidence of symptom resolution, number of patients reinitiated with ICI therapy, and IMAE recurrence upon ICI therapy reinitiation were explored as secondary endpoints. A retrospective chart review within the Allegheny Health Network was conducted in cancer patients treated with ICI therapy who developed a documented ICI-associated IMAE and subsequently received corticosteroid therapy. IRB approval was obtained for this study. Descriptive statistics were used to analyze both primary and secondary endpoints. The study sample was made up of 81 patients. Overall, 50 out of 81 patient cases (62%) were found to be discordant with guideline recommendations; the primary factors identified were inappropriate starting corticosteroid dosing (64%), initiation of a corticosteroid taper prior to IMAE resolution to at least grade 1 severity, and condensed corticosteroid taper (74%). The main IMAEs identified were colitis (28%), pneumonitis (27%), and skin-related inflammation (12%). 76 out of the 81 patients (94%) achieved IMAE resolution; 41 patients (54%) were rechallenged with ICI therapy, of which 14 patients (34%) developed IMAE recurrence. Future studies may focus on evaluating different immunosuppression strategies to optimize IMAE management.

scholarly journals Association of Immune Related Adverse Events With Efficacy of Immune Checkpoint Inhibitors and Overall Survival in Cancers: A Systemic Review and Meta-analysis

2021 ◽  
Vol 11 ◽  
Author(s):  
Yong Fan ◽  
Wenhui Xie ◽  
Hong Huang ◽  
Yunxia Wang ◽  
Guangtao Li ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Events ◽  
Cancer Patients ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Tumor Response ◽  
Checkpoint Inhibitors ◽  
Meta Analysis ◽  
Pooled Data ◽  
Cancer Types

ObjectivesImmune checkpoint inhibitors (ICIs) have brought impressive benefits to cancer patients, however often accompanied with immune-related adverse events (irAEs). We aimed to investigate the association of irAEs with efficacy and overall survival in cancer patients treated by ICIs, and further quantify the association by stratifying subgroups.MethodsPubMed, EMBASE and Cochrane library from database inception to 29 August 2019 were systematically searched. Articles reporting association of objective response rate (ORR), progression-free survival (PFS), overall survival (OS) with irAEs in cancer patients treated with approved ICIs were included. Adjusted odds ratios (OR) with 95% confidential intervals (CIs) were calculated for ORR, and hazard ratios (HR) were used for PFS and OS.ResultsA total of 52 articles comprising 9,156 patients were included. Pooled data demonstrated a statistically significant greater probability of achieving objective tumor response for patients with irAEs compared to those without (OR 3.91, 95% CI 3.05–5.02). In overall meta-analysis, patients who developed irAEs presented a prolonged PFS (HR 0.54; 95% CI 0.46–0.62) and OS (HR 0.51; 95% CI 0.41–0.59). More specifically, irAEs in certain cancer types (NSCLC and melanoma) and organs (skin and endocrine) were robustly associated with better clinical outcomes, while this association needs further verification regarding other tumors. High grade toxicities (G3–5) were not associated with a significantly favorable PFS or OS. Additionally, the association between irAEs and clinical benefit seemed to be more definite in patients receiving PD-(L)1 blockade than CTLA-4 blockade. Pooled data from landmark analyses displayed consistent results.ConclusionsThe occurrence of irAEs predicted improved tumor response and better survival in overall cancer patients treated with ICIs. Notably, the association stayed robust in certain cancer types (NSCLC and melanoma) and organ-specific irAEs (skin and endocrine).

Use of immune checkpoint inhibitors in cancer patients with pre-existing sarcoidosis

Immunotherapy ◽  
2021 ◽  
Author(s):  
Sang T Kim ◽  
Xerxes Pundole ◽  
Ramona Dadu ◽  
Olivier Lambotte ◽  
Manuel Ramos-Casals ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cancer Patients ◽  
Median Time ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Hilar Lymphadenopathy ◽  
Subcutaneous Nodules ◽  
History Of ◽  
Fluctuating Course

Aim: To evaluate adverse events in cancer patients with pre-existing sarcoidosis receiving immune checkpoint inhibitors (ICIs). Patients & methods: We retrospectively reviewed cancer patients with sarcoidosis who underwent treatment with ICI to determine frequency of sarcoidosis flares. Results: 32 patients with sarcoidosis received ICIs The median time to ICI initiation was 7 years (range: 1 month to 51 years). One patient (3%) with a 20-year remote history of sarcoidosis developed a clinically symptomatic exacerbation after three doses of atezolizumab, with hilar lymphadenopathy, subcutaneous nodules, arthritis and uveitis. Atezolizumab was discontinued and prednisone initiated. She had a fluctuating course with two additional flares. Conclusion: Frequency of flares in patients with a remote history of sarcoidosis who receive ICIs is low.

scholarly journals Severe mesenteric ischemia with multiple organ failure in a patient previously treated with a humanized monoclonal antibody against programmed death receptor-1 (pembrolizumab), a case of pembrolizumab associated catastrophic antiphospholipid syndrome?

2020 ◽  
Vol 8 ◽  
pp. 2050313X2097222
Author(s):  
E M W Mintjens-Jager ◽  
M E Vos ◽  
G Kats-Ugurlu ◽  
G A P Hospers ◽  
A Rutgers ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Multiple Organ Failure ◽  
Organ Failure ◽  
Antiphospholipid Syndrome ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Multiple Organ ◽  
Catastrophic Antiphospholipid Syndrome

Immune checkpoint inhibitors are used in the treatment of different types of tumors including melanoma and non-small cell lung carcinoma. The use of these inhibitors is associated with a broad spectrum of immune-related adverse effects. Here we report a case of a patient admitted to the intensive care unit with multiple organ failure due to catastrophic antiphospholipid syndrome following treatment with pembrolizumab, an immune checkpoint inhibitor, because of metastatic melanoma. The presented patient had multiple organ failure of lung, gastro-intestinal, renal, and the liver. Vascular thrombosis was confirmed by both imaging (pulmonary embolism on computed tomography–thorax) and histopathological examination of the intestines. In combination with the presence of IgA anti-cardiolipin antibodies and initially IgM anti-cardiolipin antibodies, catastrophic antiphospholipid syndrome was suspected. Despite treatment with plasmapheresis and corticosteroids, the patient died due to multiple organ failure. Catastrophic antiphospholipid syndrome is difficult to recognize and has high mortality rates despite supportive treatment. In this case report, discussion is provided regarding the possible immunological mechanism behind catastrophic antiphospholipid syndrome during or after treatment with immune checkpoint inhibitors. It is important to realize that in modern intensive care unit, more patients with immune-related adverse effects of the treatment with immune checkpoint inhibitors will be admitted, because of an increase in the number of patients treated with these checkpoint inhibitors. When these patients are admitted on the intensive care unit, multi-disciplinary consultation is important because of the difficulty of early recognition and optimal treatment of these possible lethal side effects.

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