The firstMIND trial (NCT04134936) evaluated the safety and efficacy of adding lenalidomide to R-CHOP+tafasitamab in the first-line treatment settings of patients with diffuse large B-cell lymphoma. To address response dynamics and the impact of measurable residual disease (MRD), we analyzed prospectively collected plasma samples from 56 study patients using the EuroClonality immunoglobulin gene (IG)-NGS assay. At baseline, disease-related clonotypes were identified in 50/56 (89%) patients by IG-NGS in cell-free (cf)DNA and/or FFPE samples. MRD markers were successfully identified in 49/52 (94%) cfDNA samples and 35/41 (85%) FFPE samples. Baseline cfDNA and circulating tumor (ct)DNA levels correlated with preclinical risk factors, and high cfDNA levels ≥3.35 log10hGE/ml plasma were significantly associated with poor progression-free survival (PFS) (hazard ratio (HR): 3.1). ctDNA clearance was rapid with 52% of patients MRD-negative at C2D1, 83% patients at C4D1, and 82% patients after finishing six 21-day cycles (end of treatment (EOT)) and a sustained treatment response (93% MRD negative) six months after EOT. ctDNA detection was associated with worse PFS outcomes at C2D1 (p = 0.039, HR:4.51, 95%Cl:0.93-21.74), C4D1 (p = 0.07, HR:3.34, 95%Cl:0.83-13.48) and EOT (p = 0.01, HR:6.38, 95%Cl:1.27-32.01) and inferior overall survival at these time points. In PET-positive patients, ctDNA-MRD had a higher specificity rendering PET/CT more precisely.

2nd Medical Department University Hospital Schleswig Holstein Kiel Germany

4th Department of Internal Medicine Hematology Charles University Hospital and Faculty of Medicine Hradec Králové Czech Republic

Clinical Biomarkers and Companion Diagnostics MorphoSys a Novartis company Planegg Planegg Germany

Clinical Development MorphoSys a Novartis company Planegg Planegg Germany

Division of Hematology Mayo Clinic Rochester MN USA

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