Ancestry-driven recalibration of tumor mutational burden and disparate clinical outcomes in response to immune checkpoint inhibitors

Free for AMP members $29 for non-members

This course contains the webinar, a handout, and continuing education credit (CME and CMLE)

Description:

Tumor Mutational Burden (TMB) is a key FDA-approved biomarker for immune checkpoint inhibitors but estimation of TMB can differ by platform and population. In this work, we show that TMB estimates from tumor-only sequencing can exhibit population specific biases due to private germline variation. Using two clinical cohorts, we investigated the interplay between genetic ancestry, TMB, and tumor-only versus tumor-normal paired sequencing in solid tumors. These biases substantially inflate TMB estimates for patients with non-European ancestry. Among patients with non-small cell lung cancer treated with ICIs, those misclassified as TMB-high from tumor-only panels did not associate with improved outcomes. We developed an ancestry-aware recalibration tool to improve the accuracy of tumor-only TMB estimates.

Learning Objectives:

Explain how tumor mutational burden is called from genomic sequencing and why it is susceptible to biases.
Demonstrate survival differences between properly classified and misclassified TMB-high patients.
Develop ancestry-based methodologies to recalibrate tumor-only TMB estimates

Speaker

Alexander Gusev, PhD
Harvard Medical School & Dana-Farber Cancer Institute

Moderator

Alanna Church, MD
Boston Children's Hospital

Duration: 1 Hour
Level of Instruction: Intermediate
Live Webinar: April 23, 2024
Date Recorded: April 23, 2024

Planned and coordinated by the Training and Education Committee

Continuing Education Credit Information

CME credit: 1.0
CMLE credit: 1.0
Date Recorded: April 23, 2024
Last day to claim credit: March 20, 2027

Accreditation Statements
AMA PRA Category 1 Credit(s)™
This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint providership of American Society for Clinical Pathology (ASCP) and Association for Molecular Pathology (AMP). The American Society for Clinical Pathology (ASCP) is accredited by the ACCME to provide continuing medical education for physicians.

The ASCP designates this enduring material for a maximum of 1.0 AMA PRA Category 1 Credit(s)™. Physicians should claim only credit commensurate with the extent of their participation in the activity.

CMLE
This continuing medical laboratory education activity is recognized by the American Society for Clinical Pathology for 1.0 hours of CMLE credit. ASCP CMLE credit hours are acceptable for the ASCP Board of Certification (BOC) Certification Maintenance Program (CMP). CMLE credit hours meet the continuing education requirements for the ASCP Board of Certification Credential Maintenance Program (CMP) and state relicensure requirements for laboratory personnel. Participants should claim only the credit commensurate with the extent of their participation in the activity.

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