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Treatment outcome of PD-1 immune checkpoint inhibitor in Asian metastatic melanoma patients: correlative analysis with PD-L1 immunohistochemistry

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Summary

Overexpression of PD-L1 has been shown to be associated with better clinical responses to PD-1/PD-L1 blockade in melanoma. However, the utility of PD-L1 immunostaining as a predictive biomarker for anti-PD-1 treatment remains unclear, especially in melanoma of acral/mucosal origin. Materials and methods We collected and reviewed the medical records of 37 patients with metastatic melanoma who were treated with the anti-PD-1 antibodies pembrolizumab or nivolumab between January and December 2015. Patients with histologically diagnosed malignant melanoma and whose pretreatment tumor specimens were available for immunohistochemical staining of PD-L1 expression in tumor or immune cells were included. Results Of 37 patients, 26 patients had either acral or mucosal melanoma. The overall response rate was 10.8 % (95 % CI, 0.8–20.8 %). The response rate to PD-1 inhibitor was 11.5 % (95 % CI, 0–23.8 %) in acral/mucosal melanoma and that for cutaneous melanoma was 9.1 % (95 % CI, 0–26.1 %). Of these 37 patients, 18 had pre-treatment tumor specimens available for PD-L1 staining. Of 18 patients, 10 (55.5 %) were of acral/mucosal origin. In all patients with acral melanoma, the overall response rate (ORR) was 16.7 % (1 of 6 patients) and disease control rate (DCR) was 50 % (3 of 6 patients). In the PDL-1(+) melanoma group (1 % cut-off value), ORR was 20 % (2/10) and DCR was 80 %; for PDL-1 (−) group, ORR was 12.5 % (1/8) and DCR of 37.5 %. In the PDL-1 (+) group by 5 % cut-off value, ORR was 33.3 % (2/6) and DCR was 83.3 %; for patients with PDL-1 (−), ORR was 8.3 % (1/12) and DCR was 50 %. The median PFS was 6.8 months in PDL-1(+) group and 1.9 months in PDL-1(−) group (p = 0.149). Anti-PD-1 treatment was very well tolerated without serious adverse events of grade 3 or 4 in all patients. Conclusions The treatment outcome to PD-1 antibody was not different in acral/mucosal melanoma when compared with cutaneous melanoma. The immunohistochemical PD-L1 expression seemed to be correlated with better clinical outcomes of anti-PD-1 treatment in limited cases.

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Acknowledgments

This work was supported by funding from the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI14C3418).

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea

    Jinhyun Cho, Kwai Han Yoo & Jeeyun Lee

  2. Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea

    Soomin Ahn & Kee-Taek Jang

  3. Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Jung Han Kim

  4. Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea

    Sang-Hee Choi

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  1. Jinhyun Cho
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Jinhyun Cho and Soomin Ahn contributed equally to this work.

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Cho, J., Ahn, S., Yoo, K.H. et al. Treatment outcome of PD-1 immune checkpoint inhibitor in Asian metastatic melanoma patients: correlative analysis with PD-L1 immunohistochemistry. Invest New Drugs 34, 677–684 (2016). https://doi.org/10.1007/s10637-016-0373-4

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