Immune checkpoint inhibitor therapy for ACTH-secreting pituitary carcinoma: a new emerging treatment?

Abstract

Background: Pituitary carcinomas are rare but aggressive and require maximally coordinated multimodal therapies. For refractory tumors, unresponsive to temozolomide (TMZ), therapeutic options are limited. Immune checkpoint inhibitors (ICI) may be considered for treatment as illustrated in the present case report.

Case: We report a patient with ACTH-secreting pituitary carcinoma, progressive after multiple lines of therapy including chemotherapy with TMZ, who demonstrated disease stabilization by a combination of ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) ICI therapy.

Discussion: Management of pituitary carcinoma beyond TMZ remains ill-defined and relies on case reports. TMZ creates, due to hypermutation, more immunogenic tumors and subsequently potential candidates for ICI therapy. This case report adds support to the possible role of ICI in the treatment of pituitary carcinoma.

Conclusion: ICI therapy could be a promising treatment option for pituitary carcinoma, considering the mechanisms of TMZ-induced hypermutation with increased immunogenicity, pituitary expression of CTLA-4 and PD-L1, and the frequent occurrence of hypophysitis as a side effect of ICI therapy.

Figure 1

Gadolinium-enhanced T1-weighted magnetic resonance imaging of the pituitary carcinoma. Panel A shows invasion of the cavernous sinus (arrow) and the metastases of the posterior fossa, left cerebellum and cervical drop metastases at the level of the dens and the third cervical vertebra (asterix) (May 2018). Panel B shows evaluation of the pituitary carcinoma after nine cycles of TMZ treatment (April 2019). Panel C shows stable disease (irRECIST criteria) 1 year after initiation of ICI (April 2020). IrRECIST, immune-related Response Evaluation Criteria in Solid Tumors; ICI, Immune Checkpoint Inhibitors.

Figure 2

Timeline of 08:00 h ACTH and UFC during follow-up. ACTH, Adrenocorticotropic hormone (08:00 h normal range: 7.2–63 ng/L); ICI, Immune Checkpoint Inhibitors; UFC, Urinary Free Cortisol (normal range: 4.2–60 µg/24 h). A full color version of this figure is available at https://doi.org/10.1530/EJE-20-0151.