The negative influence of baseline cell-free DNA on long-term survival in DLBCL depends on frontline treatment intensity - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Clinical Cancer Research Année : 2023

The negative influence of baseline cell-free DNA on long-term survival in DLBCL depends on frontline treatment intensity

Gandhi Damaj
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Diane Damotte
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Noel Milpied
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Résumé

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.

Domaines

Cancer
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Dates et versions

hal-04125745 , version 1 (13-06-2023)

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Paternité - Pas d'utilisation commerciale

Identifiants

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Fabienne Desmots-Loyer, Delphine Rossille, Mikael Roussel, Céline Pangault, Laetitia Louarn, et al.. The negative influence of baseline cell-free DNA on long-term survival in DLBCL depends on frontline treatment intensity. Clinical Cancer Research, 2023, 29 (12), pp.2280-90. ⟨10.1158/1078-0432.CCR-22-2964⟩. ⟨hal-04125745⟩
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