Learning Objectives
- To review immunotherapeutic strategies in cutaneous oncology
- Provide an overview of relevant immune therapies in skin cancer
- Discuss relevant immune pathways
https://www.themillerlab.io/presentations/harvard_derm_residents_immunotherapy_primer_08-02-2023/
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
https://www.themillerlab.io/presentations/harvard_derm_residents_immunotherapy_primer_08-02-2023/
Pre-Lecture Quiz
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https://www.themillerlab.io/presentations/harvard_derm_residents_immunotherapy_primer_08-02-2023/
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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)
- Cytokine-directed therapy
Immunotherapy in Skin Cancer
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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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
- 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)
- 4.1 mm thick
- Prognosis (10 year MSS)?
- T4aN0M0: 83%
- T3bN0M0: 81%
98%
94%
88%
82%
75%
Figure redrawn from Gershenwald et al. CA Cancer J Clin. 2017;67(6):472-492
88%
77%
60%
24%
Figure redrawn from Gershenwald et al. CA Cancer J Clin. 2017;67(6):472-492
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 |
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