Exceptional response to pembrolizumab in a metastatic, chemotherapy/radiation-resistant ovarian cancer patient harboring a pd-l1-genetic rearrangement

Stefania Bellone, Natalia Buza, Jungmin Choi, Luca Zammataro, Laurie Gay, Julia Elvin, David L. Rimm, Yuting Liu, Elena S. Ratner, Peter E. Schwartz, Alessandro D. Santin

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)

Abstract

Purpose: Ovarian carcinoma no longer responsive to surgery and chemotherapy remains an incurable disease. Alternative therapeutic options remain desperately needed. Patients and Methods: We describe a heavily pretreated patient with ovarian cancer with recurrent disease experiencing a remarkable clinical response to treatment with the anti-PD1 immune checkpoint inhibitor pembrolizumab. The clinical, pathological, and genomic characteristics of this exceptional ovarian cancer responder were carefully investigated using immunohistochemistry (IHC), quantitative multiplex fluorescence methods (i.e., automated quantitative analysis, AQUA) and whole-exome sequencing (WES) techniques. Results: The patient harbored a recurrent/metastatic radiation and chemotherapy-resistant high-grade ovarian carcinoma with clear cell features. While progressing on any standard treatment modality, she demonstrated a remarkable complete response to the anti-PD1 immune checkpoint inhibitor pembrolizumab. WES results were notable for the presence a relative low number of mutations (tumor mutation load/Mb ¼ 4.31, total mutations ¼ 164) and a peculiar structural variant disrupting the 30 region of the PD-L1 gene causing aberrant PD-L1 surface expression as confirmed by IHC and AQUA technology. Heavy infiltration of the PD-L1–mutated and PD-L1–overexpressing tumor with T-cell lymphocytes (i.e., CD4þ/CD8þ TIL), CD68þ macrophages, and CD20þ B cells was detected in the surgical specimen strongly suggesting immune evasion as a key mechanism of tumor growth and survival. Patient's complete clinical responses remain unchanged at the time of the writing of this report with no significant side effects reported to date. Conclusions: Anti-PD1 inhibitors may represent a novel treatment option for recurrent/metastatic human tumors refractory to salvage treatment harboring PD-L1 gene structural variations causing aberrant PD-L1 expression.

Original languageEnglish
Pages (from-to)3282-3291
Number of pages10
JournalClinical Cancer Research
Volume24
Issue number14
DOIs
Publication statusPublished - 2018 Jul 15
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Exceptional response to pembrolizumab in a metastatic, chemotherapy/radiation-resistant ovarian cancer patient harboring a pd-l1-genetic rearrangement'. Together they form a unique fingerprint.

Cite this