Abstract
Immune checkpoint inhibitors (icis) such as inhibitors of ctla-4, PD-1, and PD-L1, given as monotherapy or combination therapy have emerged as effective treatment options for immune-sensitive solid tumours and hematologic malignancies. The benefits of icis can be offset by immune-related adverse events (iraes) that leave all organ systems vulnerable and subsequently increase the risk for morbidity and mortality. Because of fluctuating onset and prolonged duration, the toxicities associated with iraes represent a shift from the understanding of conventional anticancer toxicities. The ctla-4 and PD-1/PD-L1 inhibitors modulate T-cell response differently, resulting in distinct toxicity patterns, toxicity kinetics, and dose-toxicity relationships. Using individualized patient education, screening, and assessment for the early identification of iraes is key to proactive management and is therefore key to improving outcomes and prolonging therapy. Management of iraes is guided by appropriate grading, which sets the stage for the treatment setting (outpatient vs. inpatient), ici treatment course (delay vs. discontinuation), supportive care, corticosteroid use, organ specialist consultation, and additional immunosuppression. Health care professionals in oncology must work collaboratively with emergency and community colleagues to facilitate an understanding of iraes in an effort to optimize seamless care.
Highlights
The use of monoclonal antibody–based immune checkpoint inhibitors such as the inhibitors of ctla-4, PD-1, and PD-L1 to manipulate the T-cell response to immunosensitive tumours has revolutionized cancer treatment[1]
The advantageous clinical outcomes associated with icis can be offset by potentially severe immune-related adverse events that are pathophysiologically unique compared with the familiar toxicities of conventional anticancer therapies
1 month; calcium and vitamin D; and prophylaxis for lower gastrointestinal bleed if risk factors are present ■■ Taper corticosteroids over at least 2–4 weeks when event reaches grade 1 or less ■■ Increased monitoring; treat as grade 3 if symptoms persist ■■ Moderate-to-severe symptoms ■■ Delay immune checkpoint inhibitor; discontinue if risk exceeds benefit ■■ Oral corticosteroids (1–2 mg/kg)b as outpatient; consider intravenous route and hospitalization if symptoms persist for 48–72 hours, with or without additional immunosuppressionc if no response to intravenous corticosteroids in 48–72 hours ■■ Pneumocystis jiroveci prophylaxis per institutional guideline and clinical judgment if 20 mg or more prednisone daily for more than
Summary
The use of monoclonal antibody–based immune checkpoint inhibitors (icis) such as the inhibitors of ctla-4, PD-1, and PD-L1 to manipulate the T-cell response to immunosensitive tumours has revolutionized cancer treatment[1]. 1 month; calcium and vitamin D; and prophylaxis for lower gastrointestinal bleed if risk factors are present ■■ Taper corticosteroids over at least 2–4 weeks when event reaches grade 1 or less ■■ Increased monitoring; treat as grade 3 if symptoms persist ■■ Moderate-to-severe symptoms ■■ Delay immune checkpoint inhibitor; discontinue if risk exceeds benefit ■■ Oral corticosteroids (1–2 mg/kg)b as outpatient; consider intravenous route and hospitalization if symptoms persist for 48–72 hours, with or without additional immunosuppressionc if no response to intravenous corticosteroids in 48–72 hours ■■ Pneumocystis jiroveci prophylaxis per institutional guideline and clinical judgment if 20 mg or more prednisone daily for more than. In the case of corticosteroid-refractory hepatitis, mycophenolate mofetil is the preferred immunosuppressant because of the risk of additive hepatotoxicity with infliximab[10,11]
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