The Treatment of Diffuse Large B-cell Lymphoma with Poor Prognosis in the Rituximab Era – State of the Art and Future Perspectives

2010 ◽  
Vol 00 (04) ◽  
pp. 75
Author(s):  
Umberto Vitolo ◽  
Annalisa Chiappella ◽  
Chiara Frairia ◽  
Barbara Botto ◽  
◽  
...  
Keyword(s):  
B Cell ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
High Dose ◽  
Phase Ii Trials ◽  
Large B Cell Lymphoma ◽  
Dose Dense ◽  
Large B Cell

Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma. The International Prognostic Index, gene profiling and early positron-emission tomography (PET) evaluation are important prognostic factors, each with a different role in predicting outcome. The addition of rituximab to standard chemotherapy – cyclophosphamide, doxorubicine, vincristine and prednisone (CHOP) – improved the outcome in elderly newly diagnosed DLBCL patients and in young patients with favourable prognostic profiles. The best treatment of young poorprognosis patients affected by DLBCL is controversial. Several phase II trials have demonstrated that the addition of rituximab to dose-dense chemotherapy CHOP14 or the addition of rituximab to high-dose chemotherapy (HDC) with peripheral stem cell transplantation were feasible and effective. The question of whether rituximab–HDC may be more effective compared with rituximab–dose-dense chemotherapy is under investigation in randomised phase III trials by major international groups. Novel therapeutic options should be investigated to increase the outcome in poor-prognosis DLBCL patients, both as single agents and in combination with standard therapy. Radioimmunotherapy, immunomodulating agents (IMiDs), dacetuzumab (SGN-40), mammalian target of rapamycin (mTOR) inihibitors, proteasome inhibitors, histone deacetylase inhibitors and anti-angiogenetic agents (anti-vascular endothelial growth factor [VEGF]) are under evaluation in clinical trials. The results will provide new insights into the treatment of DLBCL following poor prognosis.

Dose-Dense Weekly Rituximab and Standard CHOP Therapy in 123 Patients with Newly Diagnosed Diffuse Large B-Cell Lymphoma; Ganken Ariake Lymphoma Study Group Analysis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3697-3697
Author(s):  
Masahiro Yokoyama ◽  
Yasuhito Terui ◽  
Kengo Takeuchi ◽  
Hiroaki Asai ◽  
Makoto Kodaira ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Dose Dense ◽  
Weekly Cycles ◽  
Large B Cell ◽  
Chop Therapy

Abstract Abstract 3697 Poster Board III-633 BACKGROUND Originally, rituximab monotherapy for patients with relapsed or refractory aggressive lymphoma was developed with eight weekly cycles of infusions. However, in combination with R-CHOP therapy, it designed a treatment protocol of tri-weekly rituxiamb. Then four phase III studies were also reported of tri-weekly rituximab in combination with CHOP therapy. We hypothesized that a combination of eight dose-dense weekly cycles of rituximab concentrated in early initial therapy, and six cycles of standard CHOP (DR-CHOP) might result in greater improvement than that obtained with tri-weekly standard R-CHOP. PURPOSE To evaluate the clinical outcome of combination with eight dose-dense weekly cycles of rituximab and six cycles of standard CHOP (DR-CHOP) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). In addition, the pharmacokinetic (PK) parameter of serum rituximab concentration was analyzed. PATIENTS AND METHODS One hundred twenty-three patients were treated with DR-CHOP regimen in Cancer Institute Hospital from June 2003 to July 2007. All the histopathology samples were reviewed according to the WHO classification by an expert hematopathologist. Patients with transformed lymphomas from indolent B-cell lymphoma were excluded from this study. Baseline patient characteristics included a median age of 66 years (range, 24-88 years), fifty-one patients with low risk International Prognostic Index (IPI), 35 with low-intermediate IPI, 20 with high-intermediate IPI, and 17 with high IPI. In sixteen patients, prospective PK of serum rituximab concentration was analyzed. Treatments Rituximab was administered on day 1, 8, 15, 22, 29, 36, 43, and 50. CHOP followed the administration of rituximab on day 1, 22, and 43. After eight cycles of infusions of rituximab, only CHOP was administered (cycle 4-6). RESULTS At a median follow-up of 38 months, the 3-year progression-free survival and overall survival rates were 80.9% (95% confidence interval [CI], 74.0% to 87.9%) and 85.3% (95% CI, 78.8% to 91.9%), respectively. The treatment was tolerated well, and no grade 5 adverse events were observed. Maximum serum concentration of rituximab (Cmax) was 396±74 mcg /mL on day 50 (after cycle 8 of rituximab). No statistical difference in PK of serum rituximab levels was observed between relapsers and non-relapsers. CONCLUSIONS DR-CHOP was safe, feasible, and promising good clinical outcome regimen for patients with newly diagnosed DLBCL. However, this was a retrospective study, not poerwful enough to deal with efficacy. To confirm these results, larger studies are being planned to estimate the efficacy of DR-CHOP for patients with DLBCL. Now a phase III multicenter study (DR-CHOP versus standard R-CHOP) in Japan is underway. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Risk adapted high-dose and dose-dense therapies modulate the impact of biological classification in diffuse large B-cell lymphoma prognosis

Haematologica ◽  
2014 ◽  
Vol 99 (8) ◽  
pp. e138-e141 ◽  
Author(s):  
S. Montes-Moreno ◽  
A. Batlle ◽  
S. G. de Villambrosia ◽  
B. Sanchez-Espiridion ◽  
L. Cereceda ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Large B Cell Lymphoma ◽  
Biological Classification ◽  
Dose Dense ◽  
The Impact ◽  
Large B Cell

scholarly journals Elevated M-MDSCs in Circulation Are Indicative of Poor Prognosis in Diffuse Large B-Cell Lymphoma Patients

2021 ◽  
Vol 10 (8) ◽  
pp. 1768
Author(s):  
Zhitao Wang ◽  
Rui Jiang ◽  
Qian Li ◽  
Huiping Wang ◽  
Qianshan Tao ◽  
...  
Keyword(s):  
B Cell ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
Suppressor Cells ◽  
B Cell Lymphoma ◽  
Pathological Process ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Accumulation Mechanism ◽  
Large B Cell

Myeloid-derived suppressor cells (MDSCs) are defined as negative regulators that suppress the immune response through a variety of mechanisms, which usually cluster in cancer, inflammation, and autoimmune diseases. This study aims to investigate the correlation between M-MDSCs and the clinical features of diffuse large B-cell lymphoma (DLBCL) patients, as well as the possible accumulation mechanism of M-MDSCs. The level of M-MDSCs is significantly increased in newly diagnosed and relapsed DLBCL patients. Regarding newly diagnosed DLBCL patients, the frequency of M-MDSCs is positively correlated with tumor progression and negatively correlated with overall survival (OS). More importantly, the level of M-MDSCs can be defined as a biomarker for a poor prognosis in DLBCL patients. Additionally, interleukin-35 (IL-35) mediates the accumulation of M-MDSCs in DLBCL patients. Anti-IL-35 treatment significantly reduces levels of M-MDSCs in Ly8 tumor-bearing mice. Thus, M-MDSCs are involved in the pathological process of DLBCL. Targeting M-MDSCs may be a promising therapeutic strategy for the treatment of DLBCL patients.

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