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  • br Table Summary of literature about the incidence


    Table 1. Summary of literature about the incidence of immune checkpoint therapy–induced immune-related adverse effects.
    Literature Drug Adverse Total Sample Size
    Reviewed (Year) Effect Cases Reported, No. (%) Population
    Hypophysitis 12 (0.6) PD-1 axis inhibitors across clinical trials.
    Colitis 58 (2.9) Based on studies in medical
    Pneumonitis 61 (3.1) centers in various countries.
    Fatigue 67 (25) Patients recruited at 90 sites in 14 countries.
    Decreased appetite 14 (5)
    Constipation 6 (2)
    A total of 129 patients with metastatic
    Diarrhea 34 (26.4) cutaneous melanoma were identified.
    Dermatitis (rash) 18 (14.0) Princess Margaret Cancer Centre, Canada.
    81 Clinical and radiologic manifestations of irAEs in patients
    Colitis 1 (1.2) with metastatic melanoma who Moniliformin were undergoing
    Diarrhea 1 (1.2) anti-CTLA4 antibody therapy.
    Dermatitis (rash) 4 (4.9) Department of Diagnostic Radiology,
    Hypophysitis 2 (2.5) MD Anderson Cancer Center.
    Aseptic meningitis 1 (1.2)
    Arthralgia and myalgia 1 (1.2)
    Incidence of all immune-related adverse events
    Pneumonitis 94 (3.4) Based on studies in different medical
    Nephritis 9 (0.3) centers in different countries.
    El Majzoub et al
    Adverse Effects of Immune Checkpoint Therapy in Cancer Patients
    Table 1. Continued.
    Literature Drug Adverse
    Total Sample Size
    Reviewed (Year) Effect Cases Reported, No. (%) Population
    Ipilimumab and nivolumab
    Nivolumab and ipilimumab combination therapy in
    Diarrhea 197 (44.0) patients with advanced melanoma.
    Colitis 57 (12.7) Yale Comprehensive Cancer Center.
    irAE, Immune-related adverse effects; PD-1, programmed death protein 1; T1DM, type 1 diabetes mellitus.
    Allergy was defined as positive when there were entries to the allergy section of the patient’s medical record (excluding seasonal or pollen allergies). Preexisting autoimmune disease was defined as the presence of autoimmune diseases in the medical history (for example, nonsurgical hypothyroidism, type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus).
    All statistical analyses were performed with R software (version 3.3.3; R Foundation, Vienna, Austria; http:// and SPSS (version 21; IBM, Armonk, NY).
    The prevalence of various immune-related adverse effects caused by nivolumab, pembrolizumab, and ipilimumab has been thoroughly reviewed by others,31-35 and we have summarized the key reviews (case reports not included) in Table 1. Our data collection process focused on the immune-related adverse effects identified from this literature search: diarrhea,28 dermatitis28 (pruritus, rash, dermatitis, erythema, photosensitivity, toxic epidermal necrolysis, urticaria, and vitiligo), colitis,28 pneumonitis,28 hypophysitis,36 pancreatitis,37 thyroiditis,38 adrenalitis,38 nephritis,32 vasculitis,39 myocarditis,40,41 hepatitis,15,37 and hematologic42 and ophthalmologic adverse effects.43
    Characteristics of Study Subjects
    During the 5-year study period, 628 patients who received immune checkpoint therapy were identified once the exclusion criteria were applied. These patients made 1,026 visits to our ED after starting immune checkpoint
    therapy, of which 682 (66.5%) resulted in hospital admission. Approximately one quarter of the 1,026 visits were related to one or more immune-related adverse effects, and among these 257 visits, 210 (81.7%) resulted in admission. Patient demographics and clinical characteristics are summarized in Table 2. Almost half of the study cohort (45.1%) had melanoma, 55.7% had previously known allergies, and 15.8% had a history of autoimmune disease. Of the 628 patients analyzed, 179 (28.5%) were treated with more than one immune checkpoint therapy agent before ED presentation (Figure 2).
    Figure 2. Venn diagram showing the number of patients who visited the ED after initiation of immune checkpoint therapy. The number of patients receiving one treatment is presented in parentheses. The intersection areas represent concurrent or subsequent therapy.
    Adverse Effects of Immune Checkpoint Therapy in Cancer Patients El Majzoub et al
    Table 2. Patient demographics and clinical characteristics.
    Characteristic No. of Patients (%)
    Main Results
    The numbers and percentages of cancer patients presenting to the ED with various immune-related adverse effects after beginning immune checkpoint therapy were tabulated for each immune checkpoint therapy alone and in combination (Table 3). Diarrhea without the evidence of colitis was the most common immune-related adverse effect, and it appeared to be more commonly associated with ipilimumab (14.5%) and combination immune checkpoint therapy (18.4%) than with nivolumab (8.4%) or pembrolizumab (6.4%), whereas hypophysitis, thyroiditis, and pancreatitis appeared to be more commonly associated with combination immune checkpoint therapy (all 5.0%). Hepatitis was most common in patients treated with nivolumab (6.1%).