Fig. 6

Longitudinal ctDNA monitoring for disease surveillance. (A) Timeline of treatment, plasma collection, and corresponding imaging results for patient 48 (Pt_48). After initial diagnosis, the patient was treated with rituximab and bendamustine (BR), with or without zanubrutinib, followed by the R-BEAM regimen (rituximab, carmustine, etoposide, cytarabine, melphalan), highlighted in blue. A complete response (CR) was achieved following BR treatment, as confirmed by PET-CT imaging. Following auto stem cell transplant (ASCT), the patient received maintenance therapy with the ZR regimen (zanubrutinib and rituximab), marked in purple. However, PET-CT revealed progressive disease (PD), and the patient was subsequently treated with fludarabine plus cyclophosphamide (FC) and anti-CD19 CAR-T therapy but ultimately passed away on July 1, 2024. (B) ctDNA levels and log-transformed variant allele frequency (VAF) of alterations in serial plasma samples for patient 48. (C) Upset plot showing the intersections of alterations across plasma ctDNA at five time points. (D) Timeline of treatment, plasma collection, and corresponding imaging results for patient 3 (Pt_03). The patient was initially treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), achieving complete remission as confirmed by PET-CT scans. This was followed by subsequent maintenance treatments with the IR regimen (ibrutinib and rituximab) and the ZR regimen. Five longitudinal plasma samples were collected and analyzed using next-generation sequencing to monitor molecular changes over time. (E) ctDNA profiling showing the ctDNA levels and VAFs of detected alterations at various time points