Sequential immunotherapy may be beneficial for patients with cholangiocarcinoma (CCA), although its indications are still unclear, according to a case series study recently published in the American Journal of Clinical Oncology.

“This study can also serve as the foundation to build further tests on the true effectiveness and ideal duration of sequential therapy with dual immunotherapy agents,” the authors wrote.

The case series included 3 patients previously diagnosed with CCA who underwent multiple chemotherapeutic schemes, including cisplatin and gemcitabine, irinotecan and capecitabine, and immunotherapy with pembrolizumab, with no response.

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All individuals further received sequential immunotherapy with the dual checkpoint inhibitors ipilimumab and nivolumab. All of them successfully showcased a response to treatment, as evidenced by tumor marker levels or imaging studies.

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The first case was that of a 67-year-old man with CCA and metastases to the liver, lung, and lymph nodes who was diagnosed 34 months before receiving sequential immunotherapy. The second case described a 64-year-old woman with metastases to the liver, adnexa, omentum, peritoneum, and lymph nodes, diagnosed 39 months prior. The third patient was a 63-year-old man with metastases to the liver, bone, lung, and pleura who was diagnosed 43 months prior.

Importantly, none of the participants had predictive factors associated with optimal response to dual checkpoint immunotherapy, such as high tumor mutation burden or microsatellite instability. Regardless, upon failure with conventional chemotherapy, their healthcare providers decided to try sequential immunotherapy, obtaining favorable results.

These findings could serve as a starting point for further trials and research aiming to determine the benefit of using sequential immunotherapy in patients with CCA, as many details remain unclear. For example, crafting algorithms and criteria to identify which patients may benefit from this approach and when to cease conventional chemotherapy or single-drug immunotherapy and try this method is a priority.

The authors raised the question, “Should we begin to use dual immunotherapy with chemotherapy or reserve dual immunotherapy as a sequential therapy option for our patients?”


Kaakour D, Hagopian G, Lee S, Lee FC. Durable responses in patients with advanced cholangiocarcinoma on sequential dual-agent immunotherapy after progressing on single-agent immunotherapy. Am J Clin Oncol. Published online September 14, 2022. doi:10.1097/coc.0000000000000941