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Disclosure I have no relevant financial relationships with any companies related to the content of this course. Acute and Chronic Immune-Related Toxicities Implications for Long-Term Cancer Survivors Katy K. Tsai, MD Assistant Clinical

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10/10/19 Katy K. Tsai, MD Assistant Clinical Professor Melanoma & Skin Cancer Program 8th Asian Health Symposium

Acute and Chronic Immune-Related Toxicities

Implications for Long-Term Cancer Survivors

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Disclosure

I have no relevant financial relationships with any companies related to the content of this course.

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A Quick Poll…

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What subtype of cutaneous melanoma is most common in Asians?

A.

Superficial spreading melanoma

B.

Acral lentiginous melanoma

C.

Lentigo maligna melanoma

D.

Nodular melanoma

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Acral lentiginous melanoma

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This Session

§ Immunotherapy – What is it? § Immune-Related Adverse Events
  • Mechanisms of Toxicity
  • Management
§ Best Practices & Survivorship § Questions

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This Session

§ Immunotherapy – What is it? § Immune-Related Adverse Events
  • Mechanisms of Toxicity
  • Management
§ Best Practices & Survivorship § Questions

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Prsentation Title 8

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Immunotherapy is not Chemotherapy

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Immune Checkpoint Inhibition (ICI)

Figure adapted from Abdul Abbas, MD

Priming phase Anti-CTLA-4 Effector phase Anti-PD-1/L1

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FDA-approved Immune Checkpoint Inhibitors

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This Session

§ Immunotherapy – What is it? § Immune-Related Adverse Events
  • Mechanisms of Toxicity
  • Management
§ Best Practices & Survivorship § Questions

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Immune-Related Adverse Events (irAEs)

§ Unique spectrum of side effects arising from general immune system enhancement Enstoff et al, Future Oncology 2017.

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NEUROLOGIC

  • Motor/sensory neuropathy
  • Guillain-Barré syndrome
  • Autoimmune encephalitis
  • Aseptic meningitis
  • Myasthenia gravis

ENDOCRINE

  • Hypophysitis
  • Thyroiditis (hyper/hypo)
  • Adrenal insufficiency
  • Diabetes (Type I)

GASTROINTESTINAL

  • Diarrhea/colitis
  • Hepatitis
  • Pancreatitis

RHEUMATOLOGIC

  • Arthralgias/myalgias
  • Myositis
  • Sicca syndrome

DERMATOLOGIC

  • Rash
  • Pruritus
  • Vitiligo
  • SJS/TEN

PULMONARY

  • Pneumonitis

CARDIAC

  • Myocarditis
  • Arrhythmias

OCULAR

  • Uveitis/scleritis
  • Conjunctivitis

RENAL

  • Nephritis (acute tubulointerstitial)

HEMATOLOGIC

  • Thrombocytopenia
  • Neutropenia
  • Red cell aplasia
  • Cryoglobulinemia

GENERAL

  • Fatigue
  • Infusion reactions

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Possible Mechanisms of Toxicity

Postow et al, N Engl J Med 2018.

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Classifying Acute vs. Chronic

Weber J et al, JCO 2012, 2017.

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Classifying Severity

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For Example…

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General Management

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Which immune checkpoint inhibitor regimen has a higher incidence of side effects, and/or more severe side effects?

A.

Ipilimumab

B.

Nivolumab

C.

Ipilimumab + nivolumab

D.

Pembrolizumab

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irAE Incidence

Larkin J et al. N Engl J Med 2015.

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All immune-related adverse events eventually resolve.

A.

True

B.

False

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Time to Resolution of Grade 3-4 irAEs

Sznol M et al, JCO 2017.

GI Skin Endocrine

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This Session

§ Immunotherapy – What is it? § Immune-Related Adverse Events
  • Mechanisms of Toxicity
  • Management
§ Best Practices & Survivorship Implications § Questions

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Best Practices

PATIENT Education § Empower early symptom reporting § Address integrative medicine concerns § Address family planning concerns § “Post-treatment teaching”
  • Transition from oncology to primary care

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Best Practices

PROVIDER Education § Risk assessment for side effects
  • Pre-existing autoimmune illness? Organ transplant?
  • Long-term steroid use
  • Medication reconciliation
§ Resources for irAE management
  • Published consensus guidelines
  • Continuing education workshops
Brahmer et al. JCO 2017. Puzanov et al. JITC 2017. NCCN Guidelines for the Management of Immunotherapy-Related Toxicities.

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Takeaway Points

§ You will care for patients who ARE RECEIVING immunotherapy, or who HAVE

RECEIVED immunotherapy and are re-integrating into primary care.

§ Overall survival has improved in so many different cancers! Continued age-

appropriate cancer surveillance and HEALTH MAINTENANCE should continue.

§ Be willing to investigate unusual complaints. Immune-related adverse events can

be ATYPICAL and/or LATE.

§ Don’t hesitate to phone a friend. Current guidelines are expert consensus-driven

rather than evidence-based (for now).

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Thank you! katy.tsai@ucsf.edu

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