Expert Opinion

Infliximab for Refractory Immunotherapy-Related Dyspnea from Pneumonitis

for Dyspnea

Infliximab is a monoclonal antibody that works against tumor necrosis factor that has been used to treat autoimmune diseases. Consideration of infliximab administration has been suggested for patients with immunotherapy-related pneumonitis that is unresponsive to systemic steroids.

Guideline / Expert Opinion

Dadu, R., Zobniw, C., & Diab, A. (2016). Managing adverse events with immune checkpoint agents. Cancer Journal, 22, 121–129. 

Purpose & Patient Population

PURPOSE: The review focuses on the description of more common immune-related adverse events (irAEs) and provides a suggested approach for the management of specific irAEs.
 
TYPES OF PATIENTS ADDRESSED: Immune checkpoint inhibitors

Type of Resource/Evidence-Based Process

RESOURCE TYPE: Expert opinion

PROCESS OF DEVELOPMENT: Expert opinion
 
SEARCH STRATEGY:
  • DATABASES USED: None
  • INCLUSION CRITERIA: None
  • EXCLUSION CRITERIA: None

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Results Provided in the Reference

Expert opinion

Guidelines & Recommendations

Dermatological toxicity (rash) is common. Risk reduction is undertaken with moisturizers; sun avoidance; avoidance of tight, rough, coarse materials next to skin; and treating skin gently. Treatment for grade 1 or 2 toxicities is topical steroids (except on face, groin, axilla, or under areas of occlusion) with oral antihistamines. Treatment for grade 3 or 4 toxicities is oral steroids.   
 
Gastrointestinal toxicities (diarrhea, colitis, obstruction, perforation) are the second most common toxicities and are dose-dependent. The workup should include a CT scan, colonoscopy, stool studies, and labs, and supportive care with intravenous fluids for hydration is advised. For mild-to-moderate (grade 1 or 2) toxicities, antimotilities are used (oral diphenoxylate HCL and atropine sulfate four times a dayand/or loperamide). If symptoms persist, oral prednisone or equivalent is used. For grade 3 or 4 toxicities, IV methylprednisolone is administered immediately. Gastroenterology consult. Infliximab produces quicker improvement in symptoms and shorter steroid treatment length. Once symptoms are resolved, steroids should be tapered over four weeks minimum. If any evidence of perforation exists, consult a surgeon and do not start antimotility agents, steroids, or infliximab.
 
For pneumonitis, seek pulmonary and ID consults. Grade 2 or greater involves hospital admission, steroids, and immune suppressants. Taper steroids over four to six weeks.

Limitations

Literature review of common checkpoint inhibitors adverse events. No quality review provided.

Nursing Implications

Further education needs to be available on the toxicity profile related to immune checkpoint inhibitors, and obtaining a detailed personal and family history of autoimmune diseases, other comorbidies, concurrent medications, PE, and medications of patients is important prior to starting therapy.

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Eigentler, T.K., Hassel, J.C., Berking, C., Aberle, J., Bachmann, O., Grunwald, V., . . . Gutzmer, R. (2016). Diagnosis, monitoring and management of immune-related adverse drug reactions of anti-PD-1 antibody therapy. Cancer Treatment Reviews, 45, 7–18. 

Purpose & Patient Population

PURPOSE: Review article
 
TYPES OF PATIENTS ADDRESSED: Programmed cell death protein 1 (PD-1) immune checkpoint pathway inhibitors/antibody adverse events reported on patients treated with these agents while participating in registry clinical trials, a retrospective review, and a consensus panel of above authors.

Type of Resource/Evidence-Based Process

RESOURCE TYPE: Expert opinion

PROCESS OF DEVELOPMENT: Review article
 
SEARCH STRATEGY:
  • DATABASES USED: None
  • INCLUSION CRITERIA: None
  • EXCLUSION CRITERIA: None

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Results Provided in the Reference

Review article

Guidelines & Recommendations

Skin events: Prevention and patient education. Topical glucocorticoids, urea-containing ointment, and oral antihistamines. Grade 3–4: hold checkpoint inhibitor, oral steroids with taper. 
 
GI events: Assess for progressive disease or infection. Grade 1: Antidiarrheal medications, oral hydration, and electrolyte supplementation. Grade 2 or higher: Colonoscopy with biopsy. Grade 2 persistent diarrhea: 0.5–1 mg/kg/day methylprednisolone or equivalent. For grade 3: 1–2 mg/kg/day methylprednisolone or equivalent administered. Taper steroids over four weeks. Immune therapy may be resumed after glucocorticoid taper. Grade 4: Permanently discontinue immune therapy.
 
Dyspnea: Tests include pulmonary function tests, chest X-ray, CT scan, and arterial blood gas. Treat with steroids based on grade. Grade 2: 1 mg/kg/day methylprednisolone or equivalent; grade 3–4: 2–4 mg/kg/day methylprednisolone or equivalent. Based on response to steroids, additional immune suppressant therapy may be needed.

Limitations

Literature review of common anti-PD-1 checkpoint pathway inhibitors/antibody therapy adverse events. No evidence of quality review provided.

Nursing Implications

Research is needed on the management of anti-PD-1 checkpoint pathway inhibitors/antibody therapy toxicities.

Print

Fay, A.P., Moreira, R.B., Nunes Filho, P.R., Albuquerque, C., & Barrios, C.H. (2016). The management of immune-related adverse events associated with immune checkpoint blockade. Expert Review of Quality of Life in Cancer Care, 1, 89–97. 

Purpose & Patient Population

PURPOSE: To review article
 
TYPES OF PATIENTS ADDRESSED: Immune checkpoint blockade therapy

Type of Resource/Evidence-Based Process

RESOURCE TYPE: Expert opinion

PROCESS OF DEVELOPMENT: Review article
 
DATABASES USED: None
 
INCLUSION CRITERIA: None
 
EXCLUSION CRITERIA: None

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Results Provided in the Reference

Review article

Guidelines & Recommendations

General guidelines: Grade 2: Treatment break until toxicity is grade 1 or less, prednisone 0.5 mg/kg/day or equivalent start if no improvement in symptoms occur after a few days. Grade 3–4: Prednisone 1–2 mg/kg/day or equivalent; after toxicity is grade 1, taper steroid over a few weeks. Immune therapy may need to be discontinued.
 
Rash: Topical steroids, such as betamethasone 0.1% or clobetasol 0.05%. Grade 2: Topical or oral steroids, such as prednisone, dosed up to 0.5 mg/kg/day or equivalent. Grade 3: IV methylprednisolone 1–2 mg/kg/day or equivalent. When rash improves, switch to oral therapy and taper carefully.
 
Diarrhea: Grade 1–2: Antidiarrheal agents, oral hydration and electrolytes, diet changes, and antimotility agents. Persisting Grade 2 diarrhea: 4–6 stool/day for more than three days; steroid 0.5 mg/kg/day prednisolone or equivalent; with improvement in diarrhea, taper steroids over four weeks. Grade 3–4: Seven stools/day or more; colonoscopy or CT abdomen; stool for leucocytes and culture; IV fluids; and IV steroids, such as methylprednisolone, 125 mg followed by oral steroids prednisone 1–2 mg/kg or equivalent. Infliximab 5 mg/kg every two weeks if colitis does not improve in 2–3 days. Taper steroids over 6–8 weeks after improvement.  
 
Dyspnea—severe toxicity: 1–2 mg/kg IV steroid; if no improvement, infliximab or other immune-suppressant agents may be used.

Limitations

Literature review of common checkpoint inhibitor adverse and serious adverse events. No evidence quality review was provided.

Nursing Implications

Research is needed on the management of checkpoint inhibitor therapy toxicities.

Print

Naidoo, J., Page, D.B., Li, B.T., Connell, L.C., Schindler, K., Lacouture, M.E., . . . Wolchok, J.D. (2016). Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies. Annals of Oncology, 27, 1362. 

Purpose & Patient Population

PURPOSE: To review the clinical studies and summarize adverse events and management algorithms
 
TYPES OF PATIENTS ADDRESSED: Patients receiving checkpoint inhibitor therapy

Type of Resource/Evidence-Based Process

RESOURCE TYPE: Expert opinion

Phase of Care and Clinical Applications

PHASE OF CARE: Active antitumor treatment

Guidelines & Recommendations

Skin rash: For grade 1, use topical corticosteroids and oral antihistamines for pruritis. For grade 2, use oral prednisone and antihistamines. For grade 3–4, hold immunotherapy and use oral steroids and antihistamines. If symptoms worsen in 48 hours, consider infliximab, cyclophosphamide, or mycophenolate mofetil.
 
Diarrhea: For grade 1, use lomotil. For worsening diarrhea, use oral corticosteroids. If diarrhea persists or worsens, use IV steroids, and if still unresolved, consider infliximab.
 
Dysypnea: For new symptoms, withhold immunotherapy and oral prednisone. For grade 3–4 pneumonitis, discontinue immunotherapy, IV corticosteroids, and prophylactic antibiotics. If it worsens in 48 hours, consider infliximab, cyclophosphamide, or mycophenolate mofetil.

Limitations

Expert opinion level information

Nursing Implications

Nurses need to be aware of potential immune-related adverse events and current recommendations for management. Although some differences in opinion exist, overall management involves the use of systemic steroids for moderate symptoms, aggressive use of IV steroids for more severe symptoms, and consideration of immunosuppression for persistent or worsening severe symptoms.

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