Combined immune checkpoint inhibitors, immunotherapy with picibanil-based intraperitoneal imiquimod, and chemotherapy in cases of advanced cervical cancer and failure of concurrent chemoradiation therapy: A new clinical paradigm

Abstract

This is a case of cervical cancer stage IIB according to the International Federation of Obstetrics and Gynecology Staging who initially presented with abnormal vaginal bloody discharge noted in August 2018. A cervical biopsy showed poorly differentiated squamous cell carcinoma, and pelvic magnetic resonance imaging revealed a 4.3-cm cervical mass involving the anterior lip, upper third of the vagina, and right parametrium without nodal or distant lesions. Although she underwent concurrent chemoradiotherapy, a residual cervical tumor was noted in April 2019. She then underwent salvage radical hysterectomy, bilateral pelvic lymph node dissection, and hyperthermic intraperitoneal chemotherapy with cisplatin in May 2019, followed by immunotherapy (picibanil-based intraperitoneal imiquimod), immune checkpoint inhibitors (pembrolizumab, atezolizumab, ipilimumab, and nivolumab), and concurrent chemoradiotherapy until March 2020. The immune risk profile showed T cell proliferation and alteration of Th1/Th2 activation after immunotherapy and immune checkpoint inhibitor therapy. There was significant increase in natural killer (NK) T cells (3.9-fold) and CD4+CD25 (4.25-fold). CD3, CD4, CD8, CD19, CD8+CD28−, and CD4/CD8 cells were increased, while CD2+CD279+ and NK cells were decreased. She received eight cycles of adjuvant chemotherapy (cisplatin, paclitaxel) and bevacizumab in June 2020 for local tumor recurrence in the pelvis which was found in April 2020. Unfortunately, she died in November 2020 due to septic shock.