Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series

Allison F O'Neill; Alanna J Church; Angela Feraco; Jennifer Spidle; Catherine B Wall; Heung Bae Kim; Scott Elisofon; Khashayar Vakili; Max Pimkin; Neekesh V Dharia; Nathan R Shelman; Antonio R Perez-Atayde; Carlos Rodriguez-Galindo

doi:10.1016/j.ebiom.2024.105147

Clinical and immunophenotype correlating with response to immunotherapy in paediatric patients with primary liver carcinoma. A case series

EBioMedicine. 2024 May 14:104:105147. doi: 10.1016/j.ebiom.2024.105147. Online ahead of print.

Affiliations

¹ Dana-Farber Cancer Institute/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Department of Pediatric Oncology, Boston, MA, USA. Electronic address: allison_oneill@dfci.harvard.edu.
² Boston Children's Hospital and Harvard Medical School, Department of Pathology, Boston, MA, USA.
³ Dana-Farber Cancer Institute/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Department of Pediatric Oncology, Boston, MA, USA.
⁴ Boston Children's Hospital and Harvard Medical School, Department of Surgery, Boston, MA, USA.
⁵ Boston Children's Hospital and Harvard Medical School, Department of Hepatology, Boston, MA, USA.
⁶ Genentech, South San Francisco, CA, USA.
⁷ University of Kentucky, Department of Pathology, Lexington, KY, USA.
⁸ St. Jude Children's Research Hospital, Departments of Global Pediatric Medicine and Oncology, Memphis, TN, USA.

Abstract

Background: Paediatric hepatocellular carcinomas (HCC) traditionally arise in the context of a normal structural and functional liver and carry a dismal prognosis. While chemotherapy is the frontline standard, there is emerging interest in the study of immunotherapies for paediatric patients with relapsed/refractory disease. There is limited data to support whether immunotherapies will be of utility in this patient population.

Methods: Six paediatric patients (median age:16 years, range: 12-17 at the time of treatment) with advanced hepatocellular neosplams, either conventional hepatocellular or fibrolamellar carcinoma, were treated with immunotherapy. Patients were consented to institutional genomic profiling and biobanking protocols. Baseline samples and serial tissue samples, when available, were evaluated for somatic mutation rate, actionable gene mutations, and pan-immune bulk RNA expression profiling. Results were correlated with clinical course.

Findings: Three patients responded to checkpoint inhibition: one achieved a complete, durable response and the other two, prolonged stable disease. Three additional patients progressed. Diagnostic tissue from the complete responder demonstrated a higher relative mutational burden and robust immune infiltrate. Pre-treatment samples from the three responders demonstrated decreased expression of genes associated with T-cell dysfunction.

Interpretation: A subset of patients with primary paediatric hepatocellular tumours will respond to immunotherapy. Immunotherapies are currently under prospective study for relapsed/refractory liver tumours in paediatric patients. Results from this report support the prospective collection of serial serum and tissue samples which may further identify genomic and immunophenotypic patterns predictive of response.

Funding: This work was supported by Philanthropic funds (Pan Mass Challenge, Team Angus and Team Perspective).

Keywords: Genomics; Hepatocellular carcinoma; Immunophenotype; Pediatric.