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National Comprehensive Cancer Network

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NCCN Flash Updates: NCCN Guidelines® and NCCN Compendium® Updated for Management of Immunotherapy-Related Toxicities

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) and the NCCN Drugs & Biologics Compendium (NCCN Compendium®) for Management of Immunotherapy-Related Toxicities. These NCCN Guidelines® are currently available as Version 1.2020.

  • Management of Immune Checkpoint Inhibitor-Related Toxicities
    • Global Changes:
      • The following footnote was added at each mention of infliximab, “An FDA-approved biosimilar is an appropriate substitute for infliximab.”
      • ICI_FTG-1 is a new page.
      • ICI_MS-3 is a new page.
    • Principles of Routine Monitoring for Immune-Checkpoint Inhibitors (IMMUNO-1) was extensively revised.
    • Infusion-Related Reactions (ICI_INF-1): The mild and moderate grade infusion-related reactions management were split and extensively revised.
    • Maculopapular Rash (ICI_DERM-1)
      • “for pruritus” was added to the 3rd bullet of Mild and Moderate Management
      • Moderate Management
        • First bullet updated: “Consider holding Continue immunotherapy”
        • 4th bullet was updated: “Treatment with moderate to high potency topical steroids...”
      • Severe Management: “consider biopsy” was added to the 4th bullet
    • Pruritus (ICI_DERM-2)
      • Mild Management: “or lidocaine patches for localized pruritus” was added to the 3rd bullet
      • Moderate Management: the 3rd bullet is new, “Consider GABA agonists (gabapentin, pregabalin)”
      • Footnote m is new: “If outpatient, consider narrow-band UVB phototherapy.”
    • Blistering Disorder (ICI_DERM-3): Recommendations for the assessment/grading and management of bullous dermatitis and SJS/TEN were extensively revised.
    • Diarrhea/Colitis (ICI_GI-1): Recommendations for diarrhea/colitis were extensively revised.
    • Hepatic Toxicity (ICI_GI-3): Footnote q is new: “Consider initiating steroids while waiting for results in cases of life-threatening transaminitis.”
    • Elevation in Amylase/Lipase (ICI_GI-5): Footnote t is new: “Mild symptoms of pancreatitis can include: nausea, bloating, belching, abdominal pain, or back pain.”
    • Acute Pancreatitis (ICI_GI-6)
      • “IV hydration” added to management of mild, moderate, and severe acute pancreatitis
      • “Follow-up over time to monitor for pancreatic insufficiency” was added to footnote bb.
    • Hyperglycemia/Diabetes Mellitus (ICI_ENDO-1)
      • Footnote c is new: “In patients who are critically ill/ill-appearing with sugars >200 mg/dL (typically 300–500 mg/dL), urgent/emergent evaluation for DKA is indicated.”
      • Footnote d was updated: “The development of type I DM is rare (1%–2%) but can be life-threatening...”
    • Thyroid Toxicity (ICI_ENDO-2)
      • Clinical, primary hypothyroidism
        • “free T4” was removed from assessment
        • Management, first sub-bullet was updated: “If TSH is >10, initiate levothyroxine therapy, oral daily ~1.6 mcg/kg or 75–100 mcg or 50–75 mcg starting dose for elderly patients with goal of getting TSH to reference range or age-appropriate range. Repeat TSH in 4–6 weeks to guide dosing changes.”
      • Thyrotoxicosis
        • “if persistent symptoms” added to first sub-bullet under assessment
        • Management, last bullet was updated: “Thyrotoxicosis often evolves to hypothyroidism (see Clinical, primary hypothyroidism above for levothyroxine dosing)
    • Hypophysitis (ICI_ENDO-3)
      • Central hypothyroidism and hypophysitis assessment was updated: “Evaluate morning cortisol and ACTH (AM), FSH...”/ Also for ICI_ENDO-4.
      • “Follow free T4 for thyroid replacement in the setting of hypophysitis-induced loss of TSH production” was added to the management of central hypothyroidism and hypophysitis.
      • “Follow free T4 for thyroid replacement in the setting of hypophysitis–induced loss of TSH production” was removed from footnote p
      • Footnote q was updated: “...Tests may show low ACTH, low morning cortisol, low Na, low K, and low testosterone, and DHEA-S...”
      • Footnote r is new: “If a patient has polyuria/polydipsia, consider workup for diabetes insipidus; however, this is exceedingly rare with only a few case reports.”
      • Footnote s was updated: “... it may also include levothyroxine for central hypothyroidism, and testosterone supplementation in males, and estrogen in pre-menopausal women if not otherwise contraindicated...”
    • Adrenal Toxicity (ICI_ENDO-4)
      • Assessment/Grading: “renin level” was removed from the 2nd bullet
      • Management
        • “and monitor electrolytes” was added to the 4th bullet
        • 3rd sub-bullet was updated: “Fludrocortisone can be started 0.1 mg daily or every other day...”
      • Footnote u is new: “To rule out central hypothyroidism.”
    • Management of Moderate Pneumonitis (ICI_PULM-1)
      • “Consider” added to 2nd bullet
      • 3rd bullet, 2nd sub-bullet was updated: “Sputum culture, blood culture, and urine culture antigen test (pneumococcus, legionella).”
      • 4th bullet was updated: “Consider bronchoscopy with bronchoalveolar lavage (BAL) to rule out infection and malignant lung infiltration (if feasible, perform bronchoscopy with BAL prior to initiation of treatment to rule out infection).
      • “with or without dry cough. Consider infectious etiologies” added to footnote a.
      • “oxygen indicated” added to footnote d.
      • Footnote h is new: “If concern for lymphangitic spread of tumor, biopsy is indicated.”
    • Severe Pneumonitis (ICI_PULM-2)
      • “Consider PFTs” removed from 4th bullet.
      • Footnote j is new: “Options are listed in alphabetical order. There is no data to support the use of one over another.”
      • Footnote l was updated: “Total dosing should be 2 g/kg, administered in divided doses over 2 to 5 days as per package insert.”
    • Renal Toxicity (ICI_RENAL-1)
      • Management of Moderate elevated serum creatinine/acute renal failure, “Consider renal biopsy” added to 3rd bullet.
      • “PPIs” added to footnote b.
      • “(consider vasculitis)” added to footnote c.
    • Ocular Toxicity (ICI_EYE-1)
      • Management of anterior uveitis, 3rd bullet was updated: “Treatment guided by ophthalmology to include ophthalmic and with or without systemic prednisone/methylprednisolone”
      • Footnote f was updated: “If refractory to high-dose systemic steroids, consider adding infliximab, FDA approved biosimilar, or antimetabolites...”
    • Myasthenia Gravis (ICI_NEURO-1)
      • Assessment/Grading, 3rd bullet updated: “... aldolase, and anti-striational antibodies for possible superimposed myositis...”
      • Management of Moderate Myasthenia Gravis
        • First bullet updated: “Hold Permanently discontinue immunotherapy”
        • “Inpatient care” was added.
      • Management of Severe Myasthenia Gravis
        • “if no improvement/worsening on steroids or severe symptoms” removed from 4th bullet.
        • 4th bullet, sub-bullet is new: “Consider adding rituximab (375 mg/m2 weekly for 4 treatments or 500 mg/m2 every 2 weeks for 2 doses) if refractory to plasmapheresis or IVIG.”
      • Footnote f is new: “High-dose steroids (≥2 mg/kg/day) may exacerbate symptoms.”
    • Guillain-Barre Syndrome (ICI_NEURO-2)
      • Assessment/Grading, 5th bullet was updated: “Serum ganglioside antibody tests...”
      • Management
        • “then taper over 4 weeks” added to 3rd bullet.
        • Last bullet was updated: “Gabapentin, pregabalin, or duloxetine for pain Non-opioid management of neuropathic pain”
    • Aseptic Meningitis/Encephalitis (ICI_NEURO-4)
      • Aseptic meningitis Assessment: “if feasible” added to 3rd bullet.
      • Management of Encephalitis: “or plasmapheresis” added to 6th bullet.
      • “elevated protein” added to footnote y.
      • Footnote cc was updated: “Taper steroids rapidly over 4 weeks once symptoms resolve.”
      • Footnote dd is new: “10 mg/kg IV every 8 hours.”
    • Transverse Myelitis (ICI_NEURO-5): Assessment, last bullet was updated: “Evaluation for constipation and urinary retention with bladder scan.”
    • Cardiovascular Toxicity (ICI_CARDIO-1)
      • “Conduction abnormalities” added to Cardiovascular AE list.
      • Management of Severe or Life-Threatening were combined and extensively revised.
    • Myalgias/Myositis (ICI_MS-2)
      • Assessment/Grading
        • “and troponin” added to 2nd bullet
        • 3rd and 4th bullets are new
          • “Muscle strength testing”
          • “Consider concomitant myasthenia gravis or myocarditis”
      • Management of Mild myalgias or myositis
        • First bullet was updated: “Continue Consider holding immunotherapy”
        • The 2nd bullet is new: “Consider polymyalgia rheumatica/giant cell arteritis (see ICI_MS-3)”
        • “(eg, NSAIDs)” added to last bullet.
      • Management of moderate, severe, or life-threatening myalgias or myositis
        • 4th bullet: “Consider concomitant myasthenia gravis” was removed
        • The last two bullets are new:
          • “Consider IVIG (2 g/kg administered in divided doses per package insert)”
          • “Plasmapheresis, infliximab, or mycophenolate may be considered if refractory to steroids”
    • Principles of Immunosuppression (IMMUNO-A)
      • The name of this page was updated: “Principles of Immunosuppression for Patients Receiving Immune Checkpoint Inhibitor Immunotherapy
      • 1 of 3, Prophylaxis
        • Links to the NCCN Guidelines for Prevention and Treatment of Cancer-Related Infections were added throughout this section.
        • “Referral to physical therapy and weight-bearing exercises are recommended” added to last bullet.
      • Indications for anti-TNFα therapy (2 of 3)
        • First bullet, 2nd sub-bullet was updated: “Additional doses A second dose of anti-TNFα therapy may be required, and can should be administered 2 and 6 weeks after initial dose of infliximab or FDA-approved biosimilar.”
        • “(where infliximab is contraindicated)” was added to 2nd bullet, first sub-bullet.
    • Principles of Immunotherapy Patient Education (IMMUNO-B)
      • Page 1 of 3 was extensively revised.
      • Toxicity Management (2 of 3): 2nd bullet, 2nd sub-bullet was updated: “Delay in immunotherapy may be recommended if unclear if irAE is developing or required until AEs resolve to grade 1 or pre-treatment baseline.”
      • Patient Education Concepts (3 of 3) was extensively revised.
    • Principles of Immunotherapy Rechallenge (IMMUNO-C)
      • GI, first bullet was updated: “... In rare circumstances in which the patient cannot completely taper off steroids and symptoms are unresolved, immunotherapy may be resumed while patient is still on ≤10 mg prednisone equivalent daily. Consider concurrent vedolizumab upon resumption of PD-1/PD-L1.”
      • Liver, 2nd bullet is new: “For grade 3 hepatitis, if on CTLA-4 combined with PD-1/PD-L1, restart with just PD-1/PD-L1 inhibitor.”
      • Liver, 3rd bullet, grade 3 hepatitis was removed.
  • Management of CAR T-Cell-Related Toxicities
    • Principles of Patient Monitoring for CAR T-Cell-Related Toxicities (CART-1)
      • Before and During CAR T-Cell Infusion, 2nd bullet: “clinically significant arrhythmia” was added.
      • Post-CAR T-Cell Infusion, 2nd bullet: “or neurotoxicity” was added.
    • Cytokine Release Syndrome (CART-3)
      • Footnote l is new: “GM-CSF is not recommended in the setting of CAR T-cell therapy.”