Immunotherapy Toxicities and CRS ICANS Case Lab

Case Lab: Immunotherapy Toxicities, CRS, and ICANS

Case Snapshot

A 67-year-old on pembrolizumab for metastatic lung cancer calls with six watery stools per day, cramping, and fatigue. In the same unit, a patient is day 3 after CAR T-cell therapy with fever 39.2 C, a new oxygen requirement, and mild confusion. Both involve immune-based therapy, but nursing priorities differ by syndrome and severity.

Immune Checkpoint Inhibitor Toxicities (irAEs)

Checkpoint inhibitors (anti-PD-1 such as pembrolizumab/nivolumab, anti-PD-L1, anti-CTLA-4 such as ipilimumab) unleash T-cell activity against tumor and against normal tissue. Immune-related adverse events can hit skin, colon, liver, lung, endocrine organs, kidney, heart, nerves, eyes, or joints, and may appear weeks to months after the last dose, including after a patient lands in an ED that does not know the history. First-line treatment for grade 2+ irAEs is corticosteroids per oncology order, not loperamide or empiric antibiotics.

The patient with six watery stools per day is at grade 2 colitis (4-6 stools/day above baseline). Do not advise routine loperamide and continued therapy; loperamide can mask worsening colitis. Assess stool count above baseline, hydration, fever, blood, abdominal pain, and intake, then notify the provider, who may hold the drug, order stool studies to exclude infection, and start corticosteroids; steroid-refractory colitis escalates to infliximab. RN scope is assessment, triage, education, and protocol care, not diagnosing colitis or prescribing steroids.

CRS Recognition and Grading

Cytokine release syndrome (CRS) follows CAR T-cell therapy and some bispecific antibodies. Fever is usually the first sign. The ASTCT consensus grades by the worst parameter among fever (>=38 C), hypotension, and hypoxia: Grade 1 is fever alone; higher grades add escalating hypotension and oxygen need. Know the product-specific monitoring window, fever protocol, and whether tocilizumab (anti-IL-6 receptor) and corticosteroids are available. For the day-3 patient with fever and new oxygen need, obtain vitals, SpO2, hemodynamics, mental status, IV access, and infection-workup orders, then notify the provider immediately.

Sepsis and CRS look alike and both demand urgent action; do not dismiss fever as expected.

ICANS Recognition

Immune effector cell-associated neurotoxicity syndrome (ICANS) includes confusion, word-finding difficulty, tremor, handwriting deterioration, decreased consciousness, seizure, cerebral edema, or motor weakness. It is graded with the 10-point ICE score (orientation, naming, following commands, writing, attention) plus level of consciousness, seizures, motor findings, and signs of raised intracranial pressure. A small change matters: a patient who cannot name the year, write a familiar sentence, or follow commands needs escalation.

Critically, tocilizumab treats CRS but does not treat ICANS and may worsen it because it does not cross the blood-brain barrier well; ICANS is managed with corticosteroids and supportive seizure precautions per protocol.

Patient Education and Documentation

Checkpoint-inhibitor patients must report promptly: new diarrhea, cough, dyspnea, rash, jaundice, severe fatigue, headache, vision changes, mood or cognition changes, chest pain, or decreased urine. They carry an immunotherapy wallet card, tell every clinician (including the ED), and avoid starting steroids, antidiarrheals, supplements, or antibiotics without oncology guidance. Cellular-therapy patients need fever and neurologic instructions, caregiver monitoring, a driving restriction (typically 8 weeks), proximity-to-center requirements, and infection precautions.

Document baseline and current symptoms, therapy type and date, grading elements (ICE score, fever, SpO2, blood pressure), provider notification, orders, response, and education. Reassess often, because CRS and ICANS can worsen within hours.

Grading Logic and Exam Traps

The ASTCT consensus is graded by the single worst parameter, so a patient with only fever is Grade 1 even if other vitals are normal, while a patient needing high-flow oxygen and pressors is Grade 3-4 regardless of how mild the fever was. After a patient has received tocilizumab or steroids, fever is no longer required to grade subsequent CRS severity, because antipyretic effects mask it; grading then leans on hypotension and hypoxia.

The ICE score's ten points come from orientation (4), naming three objects (3), following a command (1), writing a sentence (1), and counting backward from 100 by tens (1); a drop in handwriting quality is an early, easily missed ICANS sign.

High-yield distinctions and traps:

• Pseudoprogression with checkpoint inhibitors means a tumor can appear to enlarge before shrinking; teach patients not to assume failure from one scan, and do not stop therapy on imaging alone.
• Treating immune colitis with empiric antibiotics instead of corticosteroids is a wrong answer; antibiotics are added only if infection (such as C. difficile) is suspected.
• Giving acetaminophen to a febrile CAR T-cell patient before cultures can mask the picture and is a distractor; assess and escalate first.
• The CAR T-cell driving restriction (typically 8 weeks) and caregiver proximity rules exist because ICANS can develop suddenly.

On mixed immunotherapy items, the safe answer recognizes severity, follows the cellular-therapy or irAE protocol, escalates early, avoids masking symptoms without direction, and never confuses the CRS drug (tocilizumab) with ICANS management (corticosteroids).