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MMR and MSI Testing in Patients Being Considered for Checkpoint Inhibitor Therapy

Background

The US Food and Drug Administration (FDA) recently granted accelerated approval to the immune checkpoint inhibitor pembrolizumab for patients with any advanced tumor malignancy that is microsatellite instability (MSI)-high or mismatch repair (MMR) deficient. The FDA did not specify which assay should be used to assess for mismatch repair or microsatellite instability.

It is critical that practicing pathologists make informed decisions about introduction of new biomarkers into their practice. Many of new biomarkers have associated high costs both in the form of capital and reagent expenditures or as send out tests. It may be difficult to quickly access unbiased information and pathologists may find themselves unduly influenced by marketing campaigns or by focused and possibly impractical demands from other clinicians.

Scope

The primary goal of this guideline is to develop evidence-based recommendations for the testing of microsatellite instability and/or mismatch repair deficiency in patients with advanced solid tumor malignancies being considered for checkpoint inhibitor therapy.

Overarching Questions

  1. Which test modality best predicts DNA mismatch repair?
  2. Do MMR by immunohistochemistry, polymerase chain reaction, or by next generation sequencing results predict improved clinical outcomes in patients treated with checkpoint inhibitors?
  3. Does tumor mutation burden predict improved clinical outcomes in patients treated with checkpoint inhibitors?

Status

Research and Review

Collaborators

Association for Molecular Pathology
American Society of Clinical Oncology
Fight Colorectal Cancer

Expert Panel Members

Russell Broaddus, MD, PhD, FCAP, Chair
Sarah F. Adams, MD
Angela Bartley, MD, FCAP
Heather Hampel, MS, LGC
Brooke Howitt, MD
Wenora Johnson – patient advocate
Sarah Kerr, MD
Eric Konnick, MD, MS, FCAP

Cristina Magi-Galuzzi, MD, PhD
Ann M. Mills, MD
Michael J. Overman, MD – ASCO
Antonia R. Sepulveda, MD, PhD, FCAP – AMP
Zsofia K. Stadler, MD – ASCO
Carol Colasacco, MLIS, SCT(ASCP)
Lesley Souter, PhD
Christina B. Ventura, MPH, MT(ASCP)

Review more upcoming CAP evidence-based guidelines by the Center.

Public Comment Period

Share your voice by 10/31/19—biomarker testing for diffuse gliomas draft recommendations

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