Efficacy of immune checkpoint inhibitors (ICI) in patients with advanced pancreatic NETs displaying high TMB and MMR alterations following treatment with alkylating agents

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Introduction: Alkylating chemotherapy (ALK) is frequently used in patients with PanNETs. It may favour grade progression and acquisition of a hypermutator phenotype associated with frequent alterations of the MMR genes, suggesting a potential benefit of ICI.

Aim(s): We aimed to describe the efficacy of ICI in patients with advanced PanNET pretreated with ALK.

Materials and methods: We assembled an international retrospective cohort of patients with ALK-pretreated advanced well-differentiated PanNET, who received at least one cycle of ICI. The main endpoints were progression-free survival (PFS) and objective response rate (ORR). The impact of TMB (high >10 mut/Mb) and MMR alterations (mutations or IHC) was explored.

Conference:

Presenting Author:

Authors: de Mestier L, Apostolidis L, Koumarianou A, Hernando Cubero J, Riechelmann R,

Keywords: immune checkpoint inhibitor, immunotherapy, hypermutagenicity, alkylating agents, tumour mutational burden, mismatch repair,