Ig-HTS surveillance for disease progression/relapse (A) Patient 41 was treated for stage 1A DLBCL with R-CEOP, achieved a CR, and was monitored thereafter. Plasma ctDNA was positive on day 441 within the plasma, before detection by PET/CT and diagnosis of PD (lead time = 88 days). (B) Patient 46, diagnosed with stage IIA DLBCL, was monitored during treatment encompassing 2 separate relapses. We observed a rapid decline in plasma disease to undetectable levels as this patient achieves a partial response. On days 42 and 84, residual disease was detected by PET/CT (data not shown) despite negative plasma Ig-HTS. A subsequent PET/CT detected progression (day 140) that was also detected by Ig-HTS. The patient achieved a CR by PET/CT after salvage chemotherapy on day 223, but ultimately relapsed as detected by plasma molecular disease on day 473, confirmed by PET/CT on day 487 (lead time = 14 days). (C) Patient 48 was diagnosed with stage IVBE DLBCL with leukemic phase and bone marrow involvement. After treatment with R-CHOP, the patient achieved a CR by flow cytometry on day 228 (data not shown), at which time disease was undetectable Ig-HTS. Plasma molecular disease was detected at a level of 71 860 molecules per million genome equivalents on day 493, despite no evidence of disease on peripheral blood flow cytometry on day 493 or PET/CT (data not shown). Plasma Ig-HTS was positive 162 days before the detection of PD by flow cytometry on day 655. (D) Patient 52 was initially expectantly observed with stage IIIA indolent follicular lymphoma, at which point plasma molecular disease was negative despite clear radiographic evidence. This patient then underwent clinical and histological transformation to DLBCL in a single site that coincided with a dramatic spike in plasma molecular disease. He was treated with R-CHOP chemotherapy for DLBCL, with subsequent CR on PET/CT and normalization of plasma molecular disease.