Learning Objectives

• To review immunotherapeutic strategies in cutaneous oncology
• Provide an overview of relevant immune therapies in skin cancer
• Discuss relevant immune pathways

Disclosures

Advisory/Consultant Roles

• Pfizer
• Merck Sharpe & Dome
• Merck KGaA/EMD Serono
• Sanofi Genzyme
• Regeneron
• Checkpoint Therapeutics
• Castle Biosciences
• Incyte Corporation
• Bristol Myers Squib

Equity

• Checkpoint Therapeutics
• Avstera Therapeutics Corp

Research

• Regeneron
• Kartos Therapeutics
• NeoImmuneTech
• Xilio Therapeutics Inc

Pre-Lecture Quiz

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• Open text message app

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Overview of Immunotherapy

• The term “Immunotherapy” represents a set of therapeutic strategies designed to enhance anti-tumor immunity
  
• The approach dates back, at least, to 1891 when William B. Coley, a sarcoma surgeon at Memorial Hospital in New York, injected strepotococcal organisms into a patient with inoperable cancer
  

Current IO Strategies

• Today, a variety of approaches exist, for example:

  • Cytokine-directed therapy
    
  • TLR agonism
    
  • Immune-checkpoint blockade
    
  • Oncolytic viral therapy
    
  • Bispecific T-cell engagers
  • Chimeric Antigen Receptor (CAR) T cells
    
  • Tumor-Infiltrating Lymphocytes (TILs)

Immunotherapy in Skin Cancer

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Case HPI

• Male in the 8th decade of life
  
• Presents with a 2.8 cm poorly differentiated peri-orbital CSCC

Case Work Up

• Outside PET-CT showed no evidence of regional or metastatic disease

How would you manage this patient?

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Let’s Review

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Case - HPI

• 71-year-old Fitzpatrick skin type 2 male with no significant PMH presents with this lesion on his chest x 3 months

Case - Work Up

• Excisional biopsy performed.
  
• Pathology revealed a 4.1 mm thick, non-ulcerated, superficial spreading melanoma. Mitotic rate 9 per mm². LVI present. Tumor infiltrating lymphocytes present, non-brisk. No microsatelites.
  
• Subsequent PET-CT and brain MRI demonstrated no regional or distant metastases.
  

Case - Management

• WLE with 2 cm margins
  • no tumor on ink
    
• SLNBx with 0/2 nodes positive
  
• BRAF Wild Type

• Stage ?
  • 4.1 mm thick
    
  • no ulceration
    
  • Neg SLNBx
    
  • No mets
    
  • Stage IIB (T4aN0M0)
• Prognosis (10 year MSS)?
  • T4aN0M0: 83%
  • T3bN0M0: 81%

98%

94%

88%

82%

75%

88%

77%

60%

24%

What are your next steps in management?

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Summary

• Immunotherapy is a term that encompasses several therapeutic strategies that utilize the immune system as a therapy against cancer
  
• In skin cancer, the most relevant immunotherapeutic strategies in 2022 include:

IO in Skin Cancer

IO Mechanism	Examples
Checkpoint Inhibition	CTLA-4: Ipilimumab PD-1: Pembrolizumab, Nivolumab, Cemiplimab, Retifanlimab PD-L1: Avelumab, Atezolizumab LAG-3: Relatlimab
Bispecific T-cell engagers	Tebentafusp
Oncolytic Viruses	Talimogene laherparepvec
Cytokine Therapy	Interferon Alfa-2a, Interferon Alfa-2b, Interleukin-2
TLR Agonism	Imiquimod

Post Lecture Quiz

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