Article ; Online: The Negative Influence of Baseline Cell-free DNA on Long-term Survival in DLBCL Depends on Frontline Treatment Intensity.
Clinical cancer research : an official journal of the American Association for Cancer Research
2023 Volume 29, Issue 12, Page(s) 2280–2290
Abstract: 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 ...
| Abstract | 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. |
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| MeSH term(s) | Humans ; Hematopoietic Stem Cell Transplantation ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Disease-Free Survival ; Cell-Free Nucleic Acids ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Transplantation, Autologous ; Lymphoma, Large B-Cell, Diffuse/drug therapy ; Rituximab/therapeutic use ; Vincristine ; Doxorubicin ; Cyclophosphamide |
| Chemical Substances | Antibodies, Monoclonal, Murine-Derived ; Cell-Free Nucleic Acids ; Rituximab (4F4X42SYQ6) ; Vincristine (5J49Q6B70F) ; Doxorubicin (80168379AG) ; Cyclophosphamide (8N3DW7272P) |
| Language | English |
| Publishing date | 2023-04-04 |
| Publishing country | United States |
| Document type | Randomized Controlled Trial ; Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 1225457-5 |
| ISSN | 1557-3265 ; 1078-0432 |
| ISSN (online) | 1557-3265 |
| ISSN | 1078-0432 |
| DOI | 10.1158/1078-0432.CCR-22-2964 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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