Direct-on predictions

Immune checkpoint inhibitors like anti-PD-1 antibodies improve survival in advanced non-small cell lung cancer (NSCLC). However, conventional imaging often can’t identify which patients treated with these agents will benefit from such therapy. In a Cell paper published in October, a team led by Ludwig Stanford’s Ash Alizadeh and Maximilian Diehn and Matthew Hellmann of Memorial Sloan Kettering Cancer Center reported a method to accurately predict early in treatment which patients with NSCLC are likely to benefit from PD-1 checkpoint blockade. Called DIREct-On, (for Durable Immunotherapy Response Estimation by immune profiling and ctDNA-On treatment), the method incorporates three types of biomarkers to predict treatment responses: the level of mutation in tumors, changes in levels of circulating tumor DNA (ctDNA) and levels of circulating cytotoxic T cells. DIREct-On benefits from the noninvasive measurement of biomarkers not only before but during treatment as well. In preliminary studies, it accurately predicted progression-free survival from blood samples collected after one treatment cycle and was more precise than use of any of the three variables alone. Combining all three resulted in the prediction of durable clinical benefit with a sensitivity of 94% and specificity of 89%. DIREct-On could help physicians quickly determine whether anti-PD-1 immunotherapy should be continued, modified or stopped.

This article appeared in the April 2021 issue of Ludwig Link. Click here to download a PDF (1.4 MB).


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