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Multiplexed Immunofluorescence Analysis and Quantification of Intratumoral PD-1+ Tim-3+ CD8+ T Cells
Published on: February 8, 2018
The efficacy of anti-PD-1 agents in acral and mucosal melanoma
Alexander N Shoushtari1,2, Rodrigo R Munhoz3, Deborah Kuk4
1Melanoma and Immunotherapeutics Service, Memorial Sloan Kettering Cancer Center, New York, New York. shoushta@mskcc.org.
Background:
Therapeutic antibodies against programmed cell death receptor 1 (PD-1) are considered front-line therapy in metastatic melanoma. The efficacy of PD-1 blockade for patients with biologically distinct melanomas arising from acral and mucosal surfaces has not been well described.
Methods:
A multi-institutional, retrospective cohort analysis identified adults with advanced acral and mucosal melanoma who received treatment with nivolumab or pembrolizumab as standard clinical practice through expanded access programs or published prospective trials. Objective responses were determined using investigator-assessed Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Progression-free survival and overall survival were assessed using the Kaplan-Meier method.
Results:
Sixty individuals were identified, including 25 (42%) with acral melanoma and 35 (58%) with mucosal melanoma. Fifty-one patients (85%) had received previous therapy, including 77% who had previously received ipilimumab. Forty patients (67%) received pembrolizumab at a dose of 2 mg/kg or 10 mg/kg, and 20 (33%) received nivolumab at a doses ranging from 0.3 to 10 mg/kg every 2 to 3 weeks. The objective response rate was 32% (95% confidence interval, 15%-54%) in patients with acral melanoma and 23% (95% confidence interval, 10%-40%) in those with mucosal melanoma. After a median follow-up of 20 months in the acral melanoma group and 10.6 months in the mucosal melanoma group, the median progression-free survival was 4.1 months and 3.9 months, respectively. Only 2 patients (3%) discontinued treatment because of toxicity.
Conclusions:
Response rates to PD-1 blockade in patients with acral and mucosal melanomas were comparable to the published rates in patients with cutaneous melanoma and support the routine use of PD-1 blockade in clinical practice. Further investigation is needed to identify the mechanisms of response and resistance to therapy in these subtypes. Cancer 2016;122:3354-3362. © 2016 American Cancer Society.
Insights
Programmed cell death receptor 1 (PD-1) blockade shows comparable efficacy in acral and mucosal melanomas to cutaneous melanoma. These findings support the routine use of PD-1 blockade for these distinct melanoma subtypes.
Area of Science:
- Oncology
- Immunotherapy
- Dermatology
Background:
- Programmed cell death receptor 1 (PD-1) blockade is a first-line therapy for metastatic melanoma.
- The effectiveness of PD-1 blockade in acral and mucosal melanomas is not well-established.
Purpose of the Study:
- To evaluate the efficacy of PD-1 blockade in patients with advanced acral and mucosal melanomas.
- To compare response rates and survival outcomes to those seen in cutaneous melanoma.
Main Methods:
- Retrospective analysis of 60 adult patients with advanced acral or mucosal melanoma treated with nivolumab or pembrolizumab.
- Objective response rate (ORR) assessed by RECIST v1.1.
- Progression-free survival (PFS) and overall survival (OS) analyzed using Kaplan-Meier method.
Main Results:
- Objective response rates were 32% for acral melanoma and 23% for mucosal melanoma.
- Median progression-free survival was 4.1 months for acral and 3.9 months for mucosal melanoma.
- Treatment discontinuation due to toxicity was low (3%).
Conclusions:
- Response rates to PD-1 blockade in acral and mucosal melanomas are comparable to cutaneous melanoma.
- PD-1 blockade is supported for routine clinical use in these melanoma subtypes.
- Further research is needed to understand response and resistance mechanisms.
