Table 3.

Checkpoint inhibitors

Checkpoint inhibitors[54,55,56,57,58,59,60,61,64,65]	Company	Target	Indication	Common selected irAEs	Management[58,60,61,64,65]
Atezolizumab (Tecentriq)	Roche/Genentech Ltd	PD-L1	Metastatic nonsmall cell lung cancer Advanced urothelial cancer	Fatigue Diarrhea Fever Myalgias Hepatitis Pruritus Pneumonitis Dermatitis	Baseline  Perform a baseline assessment of thyroid studies, complete blood counts, liver function, and metabolic panels, grade, and document them prior to starting each treatment, and at intervals of 6-12 weeks for the first 6 months after completing treatment  Document any co-morbid conditions Evaluate baseline radiological examinations  Assess for history of autoimmune disease, which may worsen with starting a checkpoint inhibitor  Inform patients and caregivers of potential irAEs before treatment initiation Infusion irAEs  Assess for infusion related AEs  Interrupt or slow the rate of infusion for grade 1 or 2  For grade 3 or 4, permanently, discontinue the treatment General management  Assess for irAEs and manage according to grade, clinical guidelines or algorithms  Fatigue irAEs  Assess adenocorticotropic hormone, cortisol, and testosterone  Assess treatable contributing factors (gastrointestinal, hepatic, and pulmonary irAEs)  Assess psychosocial factors.  Treatment may include physical activity, psychosocial interventions, mind-body interventions, and pharmacologic interventions Dermatologic irAEs  Grade 1- Treat with topical emollients, oral antihistamines, and mild strength topical corticosteroids  Grade 2- Topical emollients, oral antihistamines, median to high strength topical steroids  Grade 3- Hold treatment, treat with topical emollients, oral antihistamines, high strength topical steroids or systemic corticosteroids depending on the severity of symptoms  Grade 4- Hold treatment, hospital admission, dermatologist referral, intravenous methylprednisolone  Gastrointestinal irAEs  Assess complete blood count, serum electrolyte panel, stool analysis for enteropathogens, and Clostridium difficile  Grade 1- Consider holding treatment, hydration, loperamide  Grade 2- Hold treatment, intravenous methylprednisolone, consider infliximab if no response to steroids. If refractory to infliximab, consider vedolizumab  Grade 3- Discontinue anti-CTLA-4, consider resuming anti-PD1/anti-PD-L1 after symptoms have resolved. Consider Gastrointestinal referral  Grade 4- Discontinue treatment permanently, hospitalization Endocrine irAEs  Thyroid  1. Check thyroid panel at baseline and prior to each treatment  2. Hormone replacement therapy for symptomatic hypothyroidism or TSH >10  3. Beta-blockers for symptomatic hyperthyroidism Diabetes mellitus  Monitor blood glucose levels with each dose  Lifestyle and diet modification as needed  Endocrine referral if symptomatic or uncontrolled blood glucose levels Hepatic irAEs  Evaluate liver function tests prior to starting every cycle of treatment  Grade 2- Hold treatment, monitor liver function tests twice weekly   If grade 2 lasts longer than 1-2 weeks, check for disease related causes, concomitant drug or alcohol administration, and infectious diseases   Treat with corticosteroids  Grade 3- Treatment should be permanently discontinued   Start corticosteroids   If no response to steroids, mycophenolate mofetil should be started   Consider hepatologist referral and liver biopsy Pulmonary irAEs  Grade 1- Hold treatment; re-evaluate in 1-2 weeks, repeat chest imaging after 3-4 weeks as needed  Grade 2- Assess for infection, monitor every 3-7 days, if no improvement in 48-72 hours, start methylprednisolone  Grade 3-4- Discontinue treatment permanently, hospital admission, referral to infectious disease Musculoskeletal irAEs  Mild- Continue treatment, NSAIDS  Moderate- Consider holding treatment, prednisone, consider rheumatology referral if symptoms do not improve  Severe- Consider discontinuation of treatment, methylprednisolone and infliximab, and rheumatology referral
Avelumab (Bavencio)	Merck	PD-L1	Metastatic Merkel cell cancer	Fatigue Myalgias Colitis Infusion reaction Dermatitis, Hypothyroidism Hyperthyroidism Hyperglycemia Nephritis Hepatitis
Durvalumab (Imfinzi)	Astra Zeneca	PD-L1	Unresectable stage III non-small cell lung cancer Urothelial cancer	Fatigue Colitis Fever Myalgias
Ipilimumab (Yervoy)	Bristol- Myers Squibb Co	CTLA-4	Melanoma Combined with Nivolumab for treatment of advanced renal cell cancer, and microsatellite instability high or mismatch repair deficient metastatic colorectal cancer	Fatigue Diarrhea Colitis Pruritus Myalgias Dermatitis Hepatitis
Nivolumab (Opdivo)	Bristol- Myers Squibb Co	PD-1	Metastatic melanoma Metastatic non-small cell lung cancer Advanced renal cell cancer Metastatic urothelial cancer Classical Hodgkin lymphoma Recurrent/metastatic squamous cell cancer of the head and neck Hepatocellular cancer	Fatigue Myalgias Dermatitis Diarrhea Hypothyroidism Colitis Hepatitis, Pneumonitis
Pembrolizumab (Keytruda)	Merck and Co Inc	PD-1	Advanced nonsmall cell lung cancer Classical Hodgkin lymphoma Advanced gastric cancer Advanced melanoma Microsatellite instability-High cancer Advanced cervical cancer Head and neck squamous cell cancer Advanced urothelial bladder cancer Primary mediastinal B-cell lymphoma	Fatigue Dermatitis Arthralgias Cough Hyperglycemia Hepatitis Pruritus

irAEs: Immune-related adverse events, CTLA-4: Cytotoxic T-lymphocyte-associated protein 4, NSAIDS: Nonsteroidal anti-inflammatory drugs, PD-1: Programmed cell death-1, TSH: Thyroid-stimulating hormone