Immunotherapy is becoming an important role in cancer care and having an understanding of immune-related adverse events (irAEs) is critical for oncology nurses to provide safe and effective patient care. Rowena Schwartz, PharmD, BCOP, of the University of Cincinnati in Ohio, discussed strategies for managing these AEs during a session at the 43rd Annual Congress in Washington, DC.

ONS offers various immunotherapy resources for nurses and patients, including treatment detail wallet cards for patients, frequently asked questions about immunotherapies, evidence-based articles, and more. The American Society of Clinical Oncology guidelines recommend that patients treated with immune checkpoint inhibitors receive timely and updated educational information and that oncology providers should have a high level of suspicion about any newly occurring symptoms.

Schwartz discussed various irAEs associated with immune checkpoint inhibitors, including dermatologic, gastrointestinal, endocrine, renal, and cardiovascular toxicities (see Table 1).

Use of these agents in older patients requires special consideration, she added. Although older patients are included in clinical trials, they may be underrepresented. Immune checkpoint inhibitors rely on the presence of ongoing immune response, and aging is associated with decreased effectiveness of the immune system. In these patients, it is important to prevent, anticipate, detect, treat, and monitor the impact of toxicities. A meta-analysis and review of nine clinical trials—including anti-CTLA4 monoclonal antibody (ipilimumab or tremelimumab) and anti PD-1 monoclonal antibody (nivolumab or pembrolizumab)—compared the use of these agents in younger and older patients. The study showed:

  • For anti-CTLA4
    • Patients < 65 years: hazard ratio (HR) = 0.82; 95% CI = 0.71–0.95; p = 0.009
    • Patients ≥ 65 years: HR = 0.77; 95% CI = 0.69–0.85; p < 0.001
  • For anti-PDL1
    • Patients < 65 years: HR = 0.68; 95% CI = 0.54–0.85; p < 0.001
    • Patients 65-75 years: HR = 0.60; 95% CI = 0.48–0.73; p < 0.001
    • Patients ≥ 75 years: HR = 0.86; 95% CI - 0.41–1.83; p = 0.70

She then discussed the link between irAEs and treatment efficacy. In a small, single-center, prospective, observational study of 38 patients with non-small cell lung cancer, irAEs appeared to be related to efficacy in those treated with nivolumab. In another single-center, retrospective review of 167 patients with solid tumors, lymphocyte count and treatment-related AEs appeared to be related to clinical response in those treated with nivolumab or pembrolizumab.

Schwartz concluded by discussing the newly approved chimeric antigen receptor (CAR) T-cell agents, which are becoming more integrated in cancer care but carry the potential for severe AEs, including cytokine release syndrome (CRS) and neurologic toxicities. In a study of tisagenlecleucel used in 75 patients with acute lymphocytic leukemia, 100% of patients experienced any-grade AEs. Of those, 99% were reported for eight or less weeks after infusion and 93% were reported eight weeks to one year after infusion. Any-grade CRS was reported in 77% of patients, and any-grade neurologic events were reported in 40% of patients.

CRS is a group of symptoms resulting from stimulation of T-cells. This AE can present as fatigue, myalgia, arthralgia, anorexia, nausea, vomiting, fever, and capillary leak syndrome. The goal of treating CRS is to manage symptoms without suppressing the CAR T-cells; thus, the initial approach should be supportive care. Targeting the cause with tocilizumab and steroids is also important. Neurologic AEs associated with CAR T-cell therapy include encephalopathy, hallucinations, delirium, and seizures.

The management of immune checkpoint inhibitors requires a coordinated approach to care, she concluded.

Table 1. Immune-Related Adverse Events by Physiology

Body System

Toxicities

Dermatologic

  • DRESS (drug reaction with eosinophilia and systemic symptoms)
  • Lyell syndrome
  • Maculopapular rash
  • Psoriasis
  • Vitiligo

Gastrointestinal

  • Celiac disease
  • Enterocolitis
  • Gastritis
  • Pancreatitis

Endocrine

  • Adrenal insufficiency
  • Diabetes
  • Hypo- or hyperthyroidism
  • Hypophysis

Renal

  • Granulomatous interstitial nephritis
  • Lupus-like glomerulonephritis

Cardiovascular

  • Cardiomyopathy
  • Myocarditis
  • Pericarditis

Pulmonary

  • Pleural effusion
  • Pneumonitis
  • Sarcoidosis

Nervous System

  • Aseptic meningitis
  • Encephalophagy
  • Guillain-Barre syndrome
  • Meningoradiculoneuritis
  • Myasthenia
  • Myelitis
  • Peripheral neuropathy

Hematologic

  • Hemolytic anemia
  • Thrombocytopenia
  • Neutropenia
  • Pancytopenia

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