PD-1 Inhibitor and GM-CSF in Oligometastatic Gallbladder Adenosquamous Carcinoma: A Case Report

Gallbladder adenosquamous carcinoma is a rare and aggressive malignancy. In patients with microsatellite-stable (MSS) and low tumor mutational burden (TMB) biliary tract tumors, PD-1/PD-L1 monotherapy yields limited responses, necessitating low-toxicity combination strategies to enhance efficacy. In this case report, an 85-year-old female with postoperative relapse of gallbladder adenosquamous carcinoma (pT2bN0M0, AJCC 8th edition, Stage IIB) presented with new oligometastatic lesions in the posterior mediastinum, supraclavicular region, and right adrenal gland after prior para-aortic radiotherapy. The patient declined chemotherapy. A 'point-and-field' regimen was implemented: stereotactic body radiotherapy (SBRT) to a dominant posterior mediastinal lymph node (95% PTV 30 Gy in 5 fractions), combined with pembrolizumab (200 mg every 3 weeks) and recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF; 150 µg subcutaneously on days 1–7 of each cycle). Abdominal pain resolved completely and Karnofsky Performance Status (KPS) improved. Serum CA19-9 levels declined from 237 U/mL to 15.4 U/mL. A 6-month follow-up PET/CT scan demonstrated a complete metabolic response of all metastatic lesions. Peripheral blood immune profiling revealed increases in CD45⁺, CD3⁺, CD8⁺ T cell, and natural killer (NK) cell counts, with a transient decrease in the CD4⁺/CD8⁺ ratio. Treatment-related adverse events were limited to grade 1 anemia, grade 1 nausea, and a grade 2 angioma-like rash. No grade ≥ 3 or late toxicities were observed. The patient passed away in June 2023 due to disease progression, having achieved a progression-free survival of 25 months and an overall survival of 29 months from treatment initiation. In this elderly patient with chemotherapy-refractory oligometastatic gallbladder adenosquamous carcinoma, we observed a durable complete metabolic response on PET/CT following treatment with SBRT, a PD-1 inhibitor, and GM-CSF, with a manageable toxicity profile in this single case. These observations generate the hypothesis that further prospective evaluation of this multimodal immunomodulatory approach may be warranted.