Advanced Cancer Outcomes After Checkpoint Immunotherapy Linked to Tumor Mutational Burden

In JAMA Network Open, a team from the University of Pennsylvania, Abramson Cancer Center, Tempus Labs, and Northwestern University highlight the importance of tumor mutational burden (TMB) as a potential treatment response marker for immunotherapy-treated advanced cancers. For their analyses, the investigators brought together targeted Tempus xT next-generation panel sequencing assay profiles and clinical data for 674 advanced cancer patients who received anti-PD-1-, anti-PD-L1-, and/or CTLA-4-targeted checkpoint immunotherapies between 2018 and 2022 to treat eight cancer types spanning more than 20 histological types. Nearly half the patients — some 49 percent — had been diagnosed with non-small cell lung cancer, they note, while bladder cancer and head and neck squamous cell carcinoma cases comprised some 22 percent and 14.2 percent of the cohort, respectively. The authors saw that enhanced TMB corresponded with longer overall survival times, progression-free survival, and time to progression than immune checkpoint inhibitor (ICI)-treated advanced cancer cases with low tumor TMB patterns. "These findings were robust to the ICI administered and remained significant after adjustment for programmed cell death-ligand 1 and microsatellite instability status," the authors report, noting that the new findings "suggest that patients identified as TMB high by the biomarker showed a significant outcome benefit to ICI therapy and should be considered for such therapy."