GL-1 Clinical recommendations on the diagnosis and use of immunotherapy in patients with deficient DNA mismatch repair (dMMR) tumors

Abstract

Historically, cancer care has been conducted based on the multifaceted evaluation of a case, such as the pathological diagnosis and staging of the disease, benefits and risks of treatments, and the patient's preference. A recent advance in molecular biology has revealed the various biological characteristics of tumors and has enabled clinical development of tumor-agnostic drugs beyond the organ-specificity of diseases. In recent years, many clinical trials have reported the efficacy of immune checkpoint inhibitors in the treatment of advanced solid tumors with dMMR. In Japan, programmed cell death-1 (PD-1) inhibitor pembrolizumab monotherapy for advanced/recurrent microsatellite instability-high (MSI-H) solid tumors, regardless of the primary tumor site, has been approved. Moreover, combination of cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) inhibitor ipilimumab and PD-1 inhibitor nivolumab have also approved for MSI-H unresectable advanced or recurrent colorectal cancer. Among with this, we are facing several clinical questions (CQs) regarding MSI/MMR tests and how this will influence the treatment and management for patients with dMMR advanced solid tumors. Therefore, we developed the clinical practice guideline. The CQs regarding medical care were formulated for patients with dMMR advanced solid tumors. Systematic reviews were performed for each clinical question for the purpose of developing clinical recommendations. Then, the committee members voted to determine the level of each recommendation considering the strength of evidence, expected risks and benefits to patients, and other factors. The guideline describes 2 clinical questions and 9 recommendations for whom, when, and how MMR status should be tested, and what is recommended for patients with dMMR advanced solid tumors. In this session, I would like to present clinical recommendations with their underlying scientific evidence as well as future perspective in this space.