Circulating tumor DNA (ctDNA) dynamics in response to checkpoint inhibitor immunotherapy in colorectal cancer.

person Kanchi Patell University Hospitals Cleveland Medical Center, Cleveland, OH info_outline Kanchi Patell, Matthew Kurian, Benjamin Booker, Michelle Chung, Alexis Bennett, David L Bajor, AMR Mohamed, Amit Mahipal, Sakti Chakrabarti, J. Eva Selfridge

Authors person Kanchi Patell University Hospitals Cleveland Medical Center, Cleveland, OH info_outline Kanchi Patell, Matthew Kurian, Benjamin Booker, Michelle Chung, Alexis Bennett, David L Bajor, AMR Mohamed, Amit Mahipal, Sakti Chakrabarti, J. Eva Selfridge Organizations University Hospitals Cleveland Medical Center, Cleveland, OH, Case Western Reserve University, Cleveland, OH, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH, University Hospital Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, UH Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, University Hospital Seidman Cancer Center, Cleveland, OH, University Hospitals, Cleveland Medical Center - Seidman Cancer Center, Cleveland, OH Abstract Disclosures Research Funding No funding received None. Background: Circulating tumor DNA (ctDNA) is emerging as a sensitive and specific non-invasive marker of active disease in patients (pts) with colorectal cancer (CRC) and may be used for monitoring response to immunotherapy (IO) in all solid tumors. However, the dynamics of ctDNA changes in response to IO and their correlation to radiographic response has not been well-established. Methods: We searched for all pts in our institution who received IO for a solid tumor diagnosis and who also received quantitative ctDNA testing using Signatera. We retrospectively evaluated radiographic treatment response using RECIST v1.1 and correlated radiographic response to time-matched changes in quantitative ctDNA. Objective response rate (ORR) was defined as the percentage of pts achieving radiographic partial response (PR) plus complete response (CR). Results: We identified 6 pts with advanced CRC who underwent serial ctDNA testing while receiving IO; all patients had loss of mismatch repair protein expressions. Median age was 70 years (range 35-90), and 50% of patients were female. All pts were actively receiving IO at the time of data cutoff. Two pts were receiving ipilimumab plus nivolumab, the other 4 pts were receiving pembrolizumab; 1 pt had only received 1 cycle of IO at time of cutoff, thus did not have on-treatment imaging and was excluded from further analysis. For the response evaluable patients, ORR was 100%, with all pts (5/5) achieving PR after median of 3 cycles (range 1-3 cycles) of treatment. Quantitative ctDNA decreased by 83-100% in all pts analyzed. 1 pt had radiographic (pseudo-)progression at time of first radiographic assessment, however at this timepoint, ctDNA had decreased by 60%; this pt continued on immunotherapy based on clinical benefit including ctDNA data. Subsequent radiographic assessment of this pt confirmed partial response and ctDNA response decreased by total of 95% after a total of 3 cycles of IO. Conclusions: In this small patient population, we show that quantitative ctDNA directly corresponds to radiographic response to IO, and may guide treatment decisions by differentiating pseudoprogression from true progression. Further longitudinal studies will show if ctDNA changes correlate to duration of response, early identification of treatment resistance, and ultimately survival.