Up-Front Immune Checkpoint Inhibitors in Patients with Multiple Synchronous Primary Tumors, Including dMMR/MSI-H Gastrointestinal Malignancies: A Case Series and Review of the Literature

Abstract

Simple Summary Patients with a concurrent diagnosis of multiple primary tumors present a particularly complex challenge in terms of determining the appropriate treatment, as these patients are generally excluded from clinical trials—especially if they have other comorbidities—due in part to the risks associated with surgery. Based on the histological and molecular characteristics of the tumor, immunotherapy may be a viable non-surgical option for these patients. We describe three patients with synchronous primary tumors, including gastrointestinal tumors in which the mismatch repair status is a therapeutic target, who received immunotherapy as an alternative to other up-front therapeutic approaches. All patients achieved significant and durable disease control, with complete responses at some tumor sites and long-term survival, suggesting that in carefully selected patients, immunotherapy may represent a valid option. Further prospective studies are needed to identify patients who might benefit most and to define the optimal treatment strategy.