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

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. The GOELAMS 075 randomized clinical trial com...

Full description

Saved in:
Bibliographic Details
Published in:Clinical cancer research 2023-06, Vol.29 (12), p.2280-2290
Main Authors: Desmots, Fabienne, Rossille, Delphine, Roussel, Mikael, Pangault, Céline, Louarn, Laetitia, De Saint Jore, Mylène, Le Gouill, Steven, Bouabdallah, Krimo, Delwail, Vincent, Gressin, Remy, Cornillon, Jérôme, Damaj, Gandhi, Maisonneuve, Hervé, Damotte, Diane, Kraeber-Bodere, Françoise, Lamy, Thierry, Parrens, Marie-Cécile, Milpied, Noël, Fest, Thierry
Format: Article
Language:English
Subjects:
Antibodies, Monoclonal, Murine-Derived - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Cancer
Cell-Free Nucleic Acids
Cyclophosphamide
Disease-Free Survival
Doxorubicin
Hematopoietic Stem Cell Transplantation
Humans
Life Sciences
Lymphoma, Large B-Cell, Diffuse - drug therapy
Rituximab - therapeutic use
Transplantation, Autologous
Vincristine
Citations: Items that this one cites
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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). 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. In this randomized clinical trial, intensive regimens mitigated the negative influence of high cfDNA levels in de novo DLBCL, relative to R-CHOP.
ISSN:1078-0432
1557-3265
DOI:10.1158/1078-0432.CCR-22-2964