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Tumor Immune Profiling-Based Neoadjuvant Immunotherapy for Locally Advanced Melanoma
Lauren S Levine1, Kelly M Mahuron2, Katy K Tsai1
1Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Annals of Surgical Oncology
|June 4, 2020
Summary
Pre-treatment exhausted T cells (Tex) in advanced melanoma predict response to neoadjuvant anti-PD-1 therapy. Stratifying treatment by Tex frequency may reduce adverse events from combination immunotherapy.
Area of Science:
- Immunology
- Oncology
- Melanoma Research
Background:
- Exhausted T cells (Tex), identified as PD-1+CTLA-4+, are crucial in anti-PD-1 therapy response for metastatic melanoma.
- Assessing pretreatment Tex cell frequency in locally advanced melanoma can predict treatment outcomes.
Purpose of the Study:
- To determine if pretreatment Tex cell frequency predicts response to neoadjuvant anti-PD-1 blockade in locally advanced melanoma.
- To investigate if Tex cell frequency can guide treatment stratification and minimize adverse events.
Main Methods:
- Flow cytometry analyzed pretreatment Tex and regulatory T cell frequency in 17 locally advanced melanoma patients.
- Patients received neoadjuvant PD-1 monotherapy or PD-1/CTLA-4 combination therapy.
- Response evaluated using RECIST v1.1; recurrence-free survival (RFS) by Kaplan-Meier; adverse events by NCI-CTCAE v4.
Main Results:
- 12/17 patients achieved complete response, 4 partial response, 1 stable disease.
- 8/11 surgically treated patients had complete pathologic response.
- High objective response rates, RFS, and overall survival (OS) observed.
Conclusions:
- Immune profile-directed neoadjuvant immunotherapy shows high response rates in locally advanced melanoma.
- Stratifying treatment by Tex frequency may reduce adverse events in combination immunotherapy.
- Further validation in larger studies is warranted.
