Complete Pathological Response to Neoadjuvant Chemoimmunotherapy in a Patient With Metastatic Intrahepatic Cholangiocarcinoma With High Tumor Mutational Burden

Abstract

Intrahepatic cholangiocarcinoma (ICC) is an aggressive biliary tract cancer (BTC) with distinct anatomic, molecular, and clinical characteristics. Over the last 10-20 years, ICC has become the focus of increasing concern largely due to its rising incidence and high mortality rates in various parts of the world, including the United States.Surgery is the only potentially curative treatment option for ICC; however, recurrence rate is high, and prognosis is poor in patients with recurrent disease. The chemotherapy regimen of gemcitabine-cisplatin (GemCis) is still the standard of care for patients with unresectable metastatic ICC. There is limited data regarding pathologic ICC response to palliatively intentioned systemic treatment.Here, we report a case of a 47-year-old Caucasian male with metastatic ICC microsatellite stable (MSS) and TMB 49 mutation per megabase who achieved complete pathological response with sequential GemCis/nabpaclitaxel and pembrolizumab. This case highlights the effect of sequential neoadjuvant chemoimmunotherapy in a patient with high tumor mutational burden (TMB-H) ICC, emphasizing the importance of molecular testing, which provides valuable information that can be used in clinical practice to better select targeted chemotherapy regimens.

Intrahepatic Cholangiocarcinoma with High Microsatellite Instability and Tumor Mutation Burden That Responded Significantly to Pembrolizumab but Perforated within a Short Period

“…In the present case, pembrolizumab displayed impressive efficacy; however, a complete response was not achieved. Several cases of complete responses following pembrolizumab therapy have been reported (16,17). However, conversion surgery should be considered in order to achieve a radical cure.…”

“…However, conversion surgery should be considered in order to achieve a radical cure. One report of conversion surgery with pembrolizu- mab employed pembrolizumab after GC and nanoparticle albumin-bound paclitaxel therapy (17). In that case, pembrolizumab was administered when TMB-H was identified, as opposed to after failure of prior therapy.…”

Intrahepatic Cholangiocarcinoma With Extrahepatic Metastasis and High Tumor Mutation Burden: Case of Complete Pathological Response to Cisplatin/Gemcitabine/Pembrolizumab

“…Case reports detailing alternative clinical scenarios have been published, relating to patients with PD-L1-positive and TMB high disease, patients with advanced disease with lymph node metastases alone, or cases where management included immunotherapy 1 tyrosine kinase inhibition or triplet chemotherapy. [12][13][14]…”