Dataset Information

Rituximab-Based Therapy in Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients: Individualized Risk-Adapted Therapy Approach Using Molecular Subtypes.

ABSTRACT: Rituximab (R) with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is the current standard of care as first-line treatment for diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype. Patients who fail R-CHOP have a poor outcome with relapse or refractory disease resulting in fatality in majority of patients. This review focuses on novel therapies which are currently being assessed as first-line treatment in combination with R-CHOP in patients with DLBCL. Targeted drug development is a possibility with recent developments like gene expression profiling, RNA interference screening, DNA sequencing, identification of new biomarkers and signaling pathways. Newer drugs such as bortezomib, lenalidomide, and ibrutinib are being investigated as first-line therapy in combination with R-CHOP (XR-CHOP) in the activated B-cell (ABC) subtype of DLBCL. Additionally, inhibitors of BCL6, EZH2, and PI3K/Akt/mTOR are being considered for treatment of germinal center B-cell (GCB) subtype of DLBCL in patients with probable survival of less than 5 years. Double- or triple-hit lymphomas and double-expressor lymphomas also have poor prognosis and research to identify effective first-line therapy in these patients remains an unmet need. Presently, individualized approach that includes effective therapeutic combinations with acceptable safety profiles for use in routine practice, especially in patients likely to have poor outcomes such as relapsed/refractory DLBCL remains a distant possibility. Current evidence shows that untreated high risk patients do not have the greater benefit with use of newer drugs compared with R-CHOP. Therefore, R-CHOP remains the first-line treatment for newly diagnosed DLBCL patients.

SUBMITTER: Fan L

PROVIDER: S-EPMC7155827 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Rituximab-Based Therapy in Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients: Individualized Risk-Adapted Therapy Approach Using Molecular Subtypes.

Fan Lei L Li Lindong L Zhou Yiqun Y Li Jianyong J

Journal of hematology 20170720 2-3

Rituximab (R) with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is the current standard of care as first-line treatment for diffuse large B-cell lymphoma (DLBCL), the most common lymphoma subtype. Patients who fail R-CHOP have a poor outcome with relapse or refractory disease resulting in fatality in majority of patients. This review focuses on novel therapies which are currently being assessed as first-line treatment in combination with R-CHOP in patients with DLBCL. Targete ...[more]

PMID: 32300390

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Project description:PurposeThe addition of rituximab to standard chemotherapy has significantly improved survival in patients with lymphoma. Recently, maintenance therapy with rituximab has been shown to prevent relapse and provide survival benefits for patients with follicular or mantle cell lymphoma. However, the effects of rituximab in patients with diffuse large B-cell lymphoma (DLBCL) remain unclear. Two new studies involving rituximab in the treatment of DLBCL were performed this past year. We performed a meta analysis to evaluate the effects of rituximab maintenance treatment of patients with DLBCL.MethodsSeveral databases (PubMed, MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials) databases were reviewed for relevant randomized controlled trials published prior to May, 2016. Two reviewers assessed the quality of the included studies and extracted data independently. The hazard ratios (HRs) for time-to-event data and relative risks (RRs) for the other data were pooled and estimated.ResultsTotally 5 studies including 1740 patients were eligible for the meta-analysis. Compared to the observation group, patients who received rituximab maintenance therapy had significantly improved event-free survival (EFS) (HR = 0.80, 95% CI: 0.65-0.98) and progression-free survival (PFS) (HR = 0.72, 95% CI: 0.54-0.94). However, there was no statistically significant difference in overall survival (OS) (HR = 0.66, 95% CI: 0.27-1.29). A subgroup analysis suggested that male patients may benefit from rituximab maintenance therapy with a better EFS (HR = 0.53, 95% CI: 0.34-0.82-), while this advantage was not observed in female patients (HR = 0.99, 95% CI: 0.64-1.52).ConclusionsRituximab maintenance may provide survival benefits beyond that afforded by first- and second-line chemotherapy alone, especially in male patients. However, maintenance rituximab treatment may cause more adverse events. It is recommended that both survival benefits and adverse events should be taken into consideration when making treatment decisions.

Project description:IntroductionSoluble MHC class I-related chain A (sMICA) and B (sMICB) play a critical role tumor evolution and poor prognosis through an immune evasion mechanism. Thus, this study determines the interaction between sMICA/sMICB and the tumor immune environment in newly diagnosed diffuse large B-cell lymphoma (ND-DLBCL).MethodsWe analyzed sMICA/sMICB, cytokine in serum, and macrophage polarization analysis in tissue samples before the first chemotherapy administration. This research was performed to investigate the correlation between sMICA/sMICB expression and treatment outcomes as well as their influence on the immune system within ND-DLBCL.ResultsOf the 262 patients, 47.3% (n = 124) presented stage III or IV at diagnosis and 50.8% (n = 133) had a high International Prognostic Index (IPI ≥ 3). The patients with high (p = 0.034 and 0.004), elevated lactate dehydrogenase (p = 0.002 and 0.030), advanced stage (p = 0.003 and 0.012), and higher IPI risk (p = 0.009, and 0.032) correlated with the detection of sMICA or sMICB. The median progression-free survival (PFS) of patients with sMICA (p = 0.006) or sMICB (p =0.032) was inferior. Among the patients with advanced-stage or high IPI, those with sMICA or sMICB presented an inferior PFS and OS compared to those without. TNF-a, a pro-inflammatory cytokine, showed statistical significance with detected sMICA (p = 0.035) or sMICB (p = 0.044). Among anti-inflammatory cytokines, IL-1RA (P-value = 0.013) and IL-10 (p = 0.005) were associated with detecting sMICB, but not sMICA. In tissue samples, sMICA or sMICB detection did not correlate with the CD68/CD163 ratio.DiscussionConclusively, the identification of sMICA/sMICB presented unfavorable immunochemotherapy outcomes, and it was assumed that sMICA or sMICB and various cytokines interact, but the relationship with macrophage differentiation is unclear. Therefore, further research is needed to determine the relationship between sMICA/sMICB and tumor microenvironment in DLBCL.

Dataset Information

Rituximab-Based Therapy in Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients: Individualized Risk-Adapted Therapy Approach Using Molecular Subtypes.

Publications

Rituximab-Based Therapy in Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients: Individualized Risk-Adapted Therapy Approach Using Molecular Subtypes.

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