ctDNA-guided Therapy Optimization in Newly Diagnosed DLBCL

The feasibility of real-time ctDNA sequencing with PhasED-seq during DLBCL therapy has yet to be established. There are logistical challenges to developing a consistent and efficient workflow for obtaining, processing, and sequencing patient samples during frontline immunochemotherapy. ctDNA sequencing must be reliable with a low failure rate before it can be adopted as an integral biomarker for treatment decision making in the clinic. Furthermore, the outcomes of patients who have undetectable ctDNA with PhasED-seq during treatment who de-escalate their chemotherapy must be assessed. In this study an anticipated 40 patients with newly diagnosed DLBCL will be screened for a target enrollment goal of 32 participants. These 32 patients will receive standard treatment with 4 cycles of R-CHOP or R-pola-CHP immunochemotherapy. These patients will have blood samples collected after 3 cycles to test for the presence of ctDNA in real-time. Patients who have successful real-time sequencing and have undetected ctDNA as well as a complete remission on interim re-staging scans will de-escalate treatment and omit chemotherapy for their final 2 cycles of treatment. These patients will receive rituximab alone for their final 2 cycles. All others will continue standard treatment. 26 participants are expected to have successful real-time sequencing, of which 13 patients are expected to meet criteria for treatment de-escalation and omit chemotherapy for their final 2 cycles of treatment.