Brentuximab Vedotin + Nivolumab Clears ctDNA in 100% of Early-Stage Hodgkin Lymphoma by End of Therapy

In the SGN35-027 Part C Phase 2 study (NCT03646123), 36 stage I–II cHL (classic or early-state Hodgkin lymphoma) patients received brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine every 28 days. Baseline ctDNA was detectable in 94% (34/36) and became undetectable in 82% after one cycle (C2D1); only one patient remained ctDNA-positive at cycle 4, and all were negative at end-of-treatment. Interim PET/CT at two cycles showed 53% complete metabolic response (CMR); 16/17 PET-CMR patients had already cleared ctDNA, while 11/16 PET-partial responders with undetectable ctDNA later converted to CMR. By comparison, standard ABVD ± RT achieves ~80% PET2 negativity and five-year PFS ~90% but offers no molecular early-response marker. No ctDNA-positive samples were found at EOT, and long-term follow-up confirmed most indeterminate or partial responders converted to CMR.