The Study: Circulating tumor (ct) DNA was collected on over 200 patients receiving first-line or salvage chemo for diffuse large B-cell lymphoma (DLBCL) to assess its ability to predict event-free survival (EFS) at 2 years. Based on exploratory analysis of the initial 14 patients, a clear separation between responders and non-responders was found as early as 6 days into the first cycle with clearest distinction occurring prior to cycle 2 at day 21. Based on this, two threshold responses were defined:  early molecular response (EMR) = at least a 2 log decrease (i.e., move the decimal two places to the left) in quantitative ctDNA from baseline → day 21 and  major molecular response (MMR) = at least a 2.5 log decrease from baseline → day 42 prior to cycle 3. These metrics were validated in the proceeding 144 patients and were found to be strikingly predictive of EFS rates at 2 years: 83% vs 50% and 82% vs 46% based on achieving an EMR and MMR, respectively. EMR occurred in roughly two-thirds of patients, but can those who didn't have one still hope for an MMR? Hardly. This happened in only 4 patients, but at least those 4 outcomes were great. EMR and MMR were again validated on a second cohort of 73 patients with consistent significant associations with EFS independent of PET-response or International Prognostic Index.
Bottom Line: If ctDNA from DLBCL decreases to less than one-one hundredth of baseline after the first cycle of chemo, you can expect >80% chance of EFS at 2 years even in the salvage setting. | Kurtz, J Clin Oncol 2018