The Negative Influence of Baseline Cell-free DNA on Long-term Survival in DLBCL Depends on Frontline Treatment Intensity

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, vin-cristine and prednisone (R-CHOP) with high-dose R-chemotherapy plus autologous stem cell transplantation (R-HDT) for patients aged & LE;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 1/4 0.006]. In patients with high cfDNA levels, salvage therapy and transplantation were associated with a significantly higher OS rate. Among 50 patients with com-plete 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 regi-mens mitigated the negative influence of high cfDNA levels in de novo DLBCL, relative to R-CHOP.

Automated summary

The study aimed to investigate the relationship between the intensity of initial treatment and the baseline cell-free DNA (cfDNA) levels of DLBCL patients, and their impact on long-term survival. The results showed that a high cfDNA concentration at diagnosis was associated with poor clinical prognostic factors and independently predicted worse overall survival. High-cfDNA R-CHOP patients had worse overall survival compared to high-cfDNA R-HDT patients, but salvage therapy and transplantation improved survival in patients with high cfDNA levels.