Biotherapy, Immunotherapy, and Immune-Related Adverse Events

Biotherapy, Immunotherapy, and Immune-Related Adverse Events

Biotherapy uses biological agents (monoclonal antibodies, cytokines, vaccines, engineered immune cells) to treat cancer; immunotherapy is the dominant subgroup. Unlike cytotoxic chemotherapy, these agents often spare hair and marrow but cause inflammatory and immune emergencies. On the OCN exam this maps to both Treatment Modalities and Oncologic Emergencies items.

How Checkpoint Inhibitors Work

Immune checkpoint inhibitors (ICIs) release the brakes on T cells. Programmed cell death protein 1 (PD-1) inhibitors (nivolumab, pembrolizumab) and PD-ligand 1 (PD-L1) inhibitors (atezolizumab, durvalumab) restore T-cell recognition; cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (ipilimumab) act earlier in priming and cause more frequent, more severe toxicity, especially in combination. The same mechanism breaks immune tolerance in normal tissue, producing immune-related adverse events (irAEs).

irAEs by Organ System

CTCAE Grading Drives Management

Management follows the Common Terminology Criteria for Adverse Events (CTCAE) and society guidelines. A practical framework:

• Grade 1 (mild): usually continue therapy with closer monitoring.
• Grade 2 (moderate): usually hold the ICI and start corticosteroids such as prednisone 0.5-1 mg/kg/day.
• Grade 3-4 (severe/life-threatening): hold therapy, admit, give high-dose corticosteroids about 1-2 mg/kg/day, and add immunosuppressants (infliximab for steroid-refractory colitis) per protocol.

The RN supports grading using approved tools but does not independently grade, hold, restart, or prescribe steroids.

RN Assessment at Every Visit

Patients on immunotherapy may minimize symptoms because they feel hopeful about a new drug, so the nurse asks targeted, organ-by-organ questions rather than a generic side-effect screen. Compare bowel pattern with baseline (number and consistency of stools), review respiratory status and any new oxygen need, ask about headache and vision changes that can signal hypophysitis, quantify fatigue, and screen for new muscle weakness, chest pain, palpitations, confusion, or decreased urine output.

Laboratory monitoring commonly includes liver tests, kidney function, complete blood count, thyroid-stimulating hormone with free thyroxine, glucose, and cortisol when an endocrinopathy is suspected. The RN reports trends and clinically important changes early rather than waiting for severe symptoms, because a Grade 1 finding caught early may avoid a Grade 3 admission.

Infusion and Cytokine Risks

Some biologic agents also cause acute infusion reactions or cytokine release with fever, chills, hypotension, hypoxia, or rigors; rituximab and other CD20 antibodies are classic examples and often use premedication and a graded infusion rate. Monitoring matches the agent's risk profile and policy, including extended observation when required, and escalation is rapid for respiratory compromise, hypotension, altered mental status, chest pain, or persistent high fever.

Delayed Onset and Patient Education

irAEs are not infusion allergies. Rash and diarrhea may appear within weeks, endocrinopathies evolve over months, and toxicity can surface after the last dose. Teach patients to call for persistent diarrhea, new cough or dyspnea, yellow skin or eyes, severe headache, confusion, chest pain, palpitations, or severe rash, and to avoid self-treating significant diarrhea with antidiarrheals before calling, because masking colitis delays steroid therapy. Common misattributions trip patients up: diarrhea is blamed on food poisoning, cough on seasonal allergies, fatigue on aging.

Wallet or treatment cards help emergency clinicians who may misread an irAE as routine infection and prescribe antibiotics instead of corticosteroids. Because infection, embolism, progression, and irAEs overlap, prompt oncology involvement and clear handoffs are essential to prevent fragmented care and delayed treatment of serious organ inflammation.

The High-Mortality irAEs

Not all irAEs carry equal risk, and the exam emphasizes the lethal ones. Pneumonitis can progress from a dry cough to respiratory failure within days and is a leading cause of ICI-related death; any new or worsening dyspnea or hypoxia is treated as pneumonitis until imaging excludes it. Colitis can perforate, so high-volume or bloody diarrhea is urgent. Myocarditis is rare but carries the highest case-fatality rate of any irAE; chest pain, dyspnea, palpitations, or a troponin rise demands immediate cardiology involvement.

Hypophysitis (pituitary inflammation, most associated with CTLA-4 agents) presents insidiously with fatigue, headache, and hypotension and can precipitate adrenal crisis; it usually requires lifelong hormone replacement even after the drug stops. Diabetic ketoacidosis from autoimmune insulin deficiency and severe cutaneous reactions such as Stevens-Johnson syndrome round out the emergencies. A practical teaching anchor for patients and nurses alike: with immunotherapy, almost any new inflammation anywhere in the body could be the drug, so report early and let the team grade it rather than self-treating or waiting.

The corticosteroid course used to treat a serious irAE is usually tapered slowly over several weeks, and patients on prolonged steroids need opportunistic-infection prophylaxis, glucose monitoring, and bone protection, so the nurse reinforces not stopping steroids abruptly and watching for steroid side effects alongside the original toxicity.