Table 3. Monitoring and diagnostic testing under treatment with checkpoint inhibitors (26, 28, 31, e72).
| Generally recommended laboratory tests before and after treatment: | ||
| Baseline*1 | CBC/diff, Na, K, Ca, creatinine, CK, troponin, bilirubin, liver enzymes (AST, ALT, GGT), LDH, amylase, lipase, glucose, TSH, fT4, CRP when indicated, BUN; HIV, hepatitis A, B, C and (when indicated) CMV and EBV serology; quantiferon test when indicated, fasting cortisol when indicated | |
|
Before each cycle or once a week *1, *2 |
CBC/diff, Na, K, Ca, creatinine, CK, bilirubin, liver enzymes (AST, ALT, GGT), LDH, amylase, lipase, ‧glucose, TSH, fT4 | |
| In case of side effects | Diagnostic testing | Treatment |
| Diarrhea/colitis |
general: stool for pathogens; calprotectin in stool if indicated in case of a severe or refractory course: colonoscopy or rectosigmoidoscopy with biopsy (including staining for CMV); CMV-PCR abdominal plain film (to rule out free air due to perforation); abdominal CT if indicated |
general: rehydration; methylprednisolone 1–2 mg/kg/d in case of a severe or refractory course: infliximab 5 mg/kg i. v. |
| Hepatitis |
general: rule out viral infection, viral reactivation, or vascular cause; upper abdominal ultrasonography; if indicated, abdominal CT or liver MRI to rule out progression in case of a severe or refractory course: liver biopsy with CMV- and EBV-PCR |
general: methylprednisolone 1–2 mg/kg/d in case of a severe or refractory course: mycophenolate mofetil 1–2 g/d; if unsuccessful, anti-thymocyte-globulin (ATG) or tacrolimus |
| Pancreatitis | upper abdominal ultrasonography; if indicated, CT/MRI or magnetic resonance cholangio- pancreatigraphy (MRCP) |
symptomatic course: methylprednisolone 1 mg/kg/d |
| Endocrinopathy |
Thyroiditis: fT4, TSH, TPO-AB, TSH-receptor-AB; where indicated, thyroid scintigraphy or ultrasonography Hypophysitis: TSH, fT4, ACTH, LH, FSH, prolactin, IGF-1, estradiol, testosterone, SHBG cortisol 8:00 am; if indicated, head MRI with sella cuts |
general: for hypothyroidism: hormone substitution with thyroxine symptomatic courses: beta-blockers general: hormone substitution with hydrocortisone (e.g., 20 mg-10 mg-0); testosterone and thyroxine as indicated |
| Pneumonitis |
general: thoracic CT, pulmonary function tests in case of a severe or refractory course: bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy if indicated |
general: methylprednisolone 1 mg/kg/d; antibiotics if indicated in case of a severe or refractory course: infliximab 5 mg/kg i. v. or mycophenolate mofetil 1–2 g/d or cyclophosphamide; oxygen |
| Renal side effects | urinalysis and culture, urine microprotein analysis; 24-hour urine collection renal biopsy as indicated |
general: methylprednisolone 1 mg/kg/d |
| Cardiac side effects | CK, troponin, pro-BNP, myoglobin EKG, echocardiography coronary angiography; cardiac PET-MRT myocardial biopsy as indicated |
general: methylprednisolone 1 mg/kg/d symptomatic course: intensive care as needed in case of a severe or refractory course: unclear |
| Musculoskeletal side effects |
Myositis: CK, troponin, myoglobin, K, Ca, uric acid, muscle biopsy as indicated, rule out cardiomyositis Arthritis/rheumatic disease/temporal arteritis: ANA, ENA, dsDNA-AB, CCP-AB, RF, clinical examination of the joints, ultrasonography of the temporal artery, ultrasonography or MRI of affected joints and tendons |
general: glucocorticoids 1 mg/kg/d severe or recurrent arthritis: methotrexate or TNF-α inhibitors recurrent temporal arteritis: tocilizumab |
| Neurological side effects | neurological examination CSF examination; head MRI EEG, EMG, NCV |
general: methylprednisolone 1 mg/kg/d in case of a severe or refractory course: if indicated, methylprednisolone 1 g qd x 3–5 d (e120) |
*1 according to the authors’ experience; *2 under combination therapy (Nivo+Ipi)
ACTH: adrenocorticotrophic hormone; AB, antibody; ALT: alanine aminotransferase; ANA: antinuclear antibody; AST: aspartate aminotransferase; Ca: calcium; CBC/diff: complete blood count with differential; CCP-AB: cyclic citrulline peptide antibody; CK: creatine kinase; CMV: cytomegalovirus; CRP: C-reactive protein; CSF, cerebrospinal fluid; CT: computerized tomography;
d: day(s); dsDNA-AB: double-stranded DNA antibody; EBV: Epstein-Barr virus; EEG: electroencephalography; EKG: electrocardiogram; EMG: electromyography;
ENA: extractable nuclear antibody; FSH: follicle-stimulating hormone; fT4: free T4; GGT: gamma-glutamyl transferase; HIV: human immunodeficiency virus;
IGF-1: insulin-like growth factor-1; K: potassium; LDH: lactate dehydrogenase; LH: luteinizing hormone; MRI: magnetic resonance imaging; Na: sodium; NCV: nerve conduction velocities;
PCR: polymerase chain reaction; PET: positrone-emission tomography; pro-BNP: pro brain natriuretic peptide; qd: per day; RF: rheumatoid factor; SHBG: sex-hormone-binding globulin;
TNF: tumor necrosis factor; TPO-AB: thyroid peroxidase antibody; TSH: thyroid-stimulating hormone