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Published on: February 8, 2018
Impact of response patterns for patients with advanced acral melanoma treated with anti-programmed death-1
Li Zhou1, Lizhi Shao2, Shunyu Gao3
1Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital & Institute, 52 Fucheng Road, Haidian District, Beijing 100142, China.
Background:
Acral melanoma (AM) is less responsive to immunotherapy than nonacral cutaneous melanoma. Variable responses are seen during immunotherapy, including pseudoprogression, hyperprogressive disease (HPD) and heterogeneous responses. There are currently no studies on the response patterns of patients with AM treated with immunotherapy and the impact on the outcome.
Objectives:
To evaluate the response patterns and prognosis of patients with AM treated with anti-programmed death (PD)-1 antibodies.
Methods:
Patients with advanced AM treated prospectively in five clinical trials of anti-PD-1 monotherapy at Peking University Cancer Hospital were included. Responses of individual metastases and heterogeneous responses were evaluated during immunotherapy. Cox proportional hazards regression analysis was conducted to identify the possible predictive factors and generate a nomogram to predict the risk of 1-year and 2-year mortality.
Results:
The overall response rate was 18·0%, the disease control rate was 36·1%, median progression-free survival was 3·5 months [95% confidence interval (CI) 1·7-5·3] and median overall survival was 17·5 months (95% CI 15·1-19·9) for anti-PD-1 monotherapy. Overall, 9·8% of patients met the criteria of HPD, and displayed a dramatically worse outcome than patients without HPD. In total, 369 metastatic lesions were assessed, with the highest response rate in lymph nodes (20·4%) and the lowest in the liver (5·6%). Homogeneous response, heterogeneous response and heterogeneous or homogeneous progression had different prognoses from the best to the worst. A predictive model was constructed and achieved good accuracy with a C-index of 0·73 (95% CI 0·63-0·84) in the training set and 0·74 (95% CI 0·61-0·86) in the validation set.
Conclusions:
HPD during immunotherapy serves as an essential biomarker of poor prognosis in advanced AM. Metastases in different sites respond distinctively to immunotherapy. Clinically heterogeneous responses to immunotherapy affect the outcome of patients. A predictive model was built to distinguish the prognosis of acral melanoma under immunotherapy.
Insights
Acral melanoma (AM) shows variable responses to anti-programmed death (PD)-1 immunotherapy. Hyperprogressive disease (HPD) indicates poor prognosis, and a predictive model aids in assessing outcomes for advanced AM patients.
Area of Science:
- Oncology
- Immunotherapy
- Melanoma Research
Background:
- Acral melanoma (AM) exhibits lower responsiveness to immunotherapy compared to nonacral cutaneous melanoma.
- Variable response patterns, including pseudoprogression and hyperprogressive disease (HPD), are observed in AM patients undergoing immunotherapy.
- Limited studies exist on AM immunotherapy response patterns and their impact on patient outcomes.
Purpose of the Study:
- To evaluate the response patterns of acral melanoma (AM) patients treated with anti-programmed death (PD)-1 antibodies.
- To assess the prognostic implications of these response patterns in advanced AM.
Main Methods:
- Prospective analysis of advanced AM patients from five clinical trials of anti-PD-1 monotherapy.
- Evaluation of individual and heterogeneous metastatic responses during immunotherapy.
- Utilized Cox proportional hazards regression and developed a nomogram for mortality risk prediction.
Main Results:
- The overall response rate was 18.0% and disease control rate was 36.1% with anti-PD-1 monotherapy.
- Median progression-free survival was 3.5 months and overall survival was 17.5 months.
- Hyperprogressive disease (HPD) occurred in 9.8% of patients, associated with significantly worse outcomes. Metastatic sites showed distinct responses, with lymph nodes responding best (20.4%) and liver worst (5.6%).
- A predictive model demonstrated good accuracy (C-index 0.73-0.74) for predicting mortality risk.
Conclusions:
- Hyperprogressive disease (HPD) is a critical biomarker for poor prognosis in advanced acral melanoma (AM) treated with immunotherapy.
- Distinct metastatic responses and heterogeneous clinical responses significantly impact patient outcomes.
- A validated predictive model can effectively distinguish prognosis for AM patients undergoing immunotherapy.
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