PD-L1 Expressing Recurrent Clear Cell Carcinoma of the Vulva with Durable Partial Response to Pembrolizumab: A Case Report

Abstract

Background: The optimal treatment and molecular landscape of recurrent clear cell carcinoma of the vulva (VCCC) are unknown. No reported data exist regarding the efficacy of anti-programmed death 1 (PD-1) immune checkpoint inhibition in VCCC. We report on a patient with chemotherapy-refractory recurrent VCCC, who was found to have high tumor programmed death-ligand 1 (PD-L1) combined positive score (CPS), and subsequently experienced a durable partial response (PR), after treatment with off-label fifth-line pembrolizumab.

Case presentation: A forty-year-old Filipino woman presented to our center with recurrent VCCC that had progressed on multiple prior lines of cytotoxic chemotherapy. She had a large 25 cm fungating left groin tumor causing marked lower limb lymphedema, pain and limited mobility. PD-L1 CPS by immunohistochemistry was 45. She was treated with off-label pembrolizumab monotherapy and had a dramatic clinical, biochemical and radiological partial response. The progression-free survival of this patient's VCCC after treatment with pembrolizumab, defined as the time from initiation of pembrolizumab until disease progression (by Response Evaluation Criteria in Solid Tumors (version 1.1)), was 8 months. While receiving pembrolizumab, she was diagnosed with concurrent secondary myelodysplastic syndrome with excess blasts (MDS-EB), thought to be related to her prior exposure to multiple lines of cytotoxic chemotherapy. This eventually progressed to acute myeloid leukemia (AML), leading to her demise. Overall survival from time of initiation of pembrolizumab till death was 16 months.

Conclusion: Pembrolizumab was active in this patient with chemotherapy-refractory VCCC which harbored high PD-L1 CPS. Further studies to determine the role of immune check-point blockade in the treatment of VCCC are warranted.

Keywords: clear cell carcinoma; immune check-point blockade; immunotherapy; vulvar cancer.

Figure 1

Clinical and Radiologic Response to pembrolizumab; Immunohistochemistry. (A and B) Clinical response to pembrolizumab; (A) Fungating left groin tumor and satellite nodule at baseline (September 2018), prior to starting pembrolizumab (horizontal red arrows); (B) Dramatic clinical response after 3 cycles of pembrolizumab in primary tumor and adjacent satellite nodule (December 2018) (horizontal red arrows). (C and D) Radiologic response to pembrolizumab; (C) Baseline PET-CT showing fungating and intensely FDG-avid mass (SUVmax 19.6) at the left groin (vertical white arrow) with invasion of the adductor compartment of the left thigh; (D) Follow-up PET-CT after 6 months showing marked reduction in size and metabolic uptake (SUVmax = 3.9) of the tumor (vertical white arrow). (E) Hematoxylin and eosin x20 stain confirming clear cell carcinoma: the tumor is composed of nests of cells with round nuclei, prominent nucleoli and ample clear to eosinophilic cytoplasm; (F) Immunohistochemistry for PD-L1 using the Dako 22C3 pharmDx assay, combined positive score of 45.

Figure 2

Relevant Biochemistry and Hematology Indices during pembrolizumab treatment. Rapid reduction in serum CA-125 was observed after commencing pembrolizumab in October 2018, with CA-125 dropping precipitously from a baseline of 298 U/mL to 9.5 U/mL in December 2018, after only 3 cycles of pembrolizumab. CA-125 reached a nadir of 4.6 U/mL in February 2019. Gradual increase in CA-125 coincided with clinical disease progression in June 2019. Worsening neutropenia occurred during the course of pembrolizumab, due to underlying myelodysplastic syndrome, which was later confirmed on bone marrow examination.