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Updated: Aug 4, 2025
VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma
Published on: December 28, 2015
The Negative Influence of Baseline Cell-free DNA on Long-term Survival in DLBCL Depends on Frontline Treatment
Fabienne Desmots1,2, Delphine Rossille1,2, Mikael Roussel1,2
1Université de Rennes 1, INSERM, Établissement Français du Sang de Bretagne, UMR_S1236, Rennes, France.
Purpose:
This study aims to investigate the relationship between the intensity of the initial treatment given to patients with de novo diffuse large B-cell lymphoma (DLBCL) and the impact of their baseline cell-free DNA (cfDNA) levels on their long-term survival.
Experimental Design:
The GOELAMS 075 randomized clinical trial compared rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) with high-dose R-chemotherapy plus autologous stem cell transplantation (R-HDT) for patients aged ≤60. An interim PET assessment was used to refer patients for salvage therapy. With a median follow-up of more than 5.8 years, we analyzed the effects of the treatment arm, salvage therapy, and cfDNA level at diagnosis on overall survival (OS).
Results:
In a representative group of 123 patients, a high cfDNA concentration (>55 ng/mL) at diagnosis was associated with poor clinical prognostic factors and constituted a prognostic marker, independently of the age-adjusted International Prognostic Index. A cfDNA level above a threshold value of 55 ng/mL at diagnosis was associated with significantly worse OS. In an intention-to-treat analysis, high-cfDNA R-CHOP patients (but not high-cfDNA R-HDT patients) had worse OS [HR (95% confidence interval), 3.99 (1.98-10.74); P = 0.006]. In patients with high cfDNA levels, salvage therapy and transplantation were associated with a significantly higher OS rate. Among 50 patients with complete response 6 months after the end of treatment, for 11 of 24 R-CHOP patients, the cfDNA did not fall back to normal values.
Conclusions:
In this randomized clinical trial, intensive regimens mitigated the negative influence of high cfDNA levels in de novo DLBCL, relative to R-CHOP.
