Single nucleotide polymorphisms in ABCB1 and CBR1 can predict toxicity to R-CHOP type regimens in patients with diffuse non-Hodgkin lymphoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Jordheim LP
PROVIDER: S-EPMC4420233 | biostudies-literature | 2015 May
REPOSITORIES: biostudies-literature
Publications
Single nucleotide polymorphisms in ABCB1 and CBR1 can predict toxicity to R-CHOP type regimens in patients with diffuse non-Hodgkin lymphoma.
Jordheim Lars P LP Ribrag Vincent V Ghesquieres Hervé H Pallardy Sophie S Delarue Richard R Tilly Hervé H Haioun Corinne C Jardin Fabrice F Demangel Delphine D Salles Gilles A GA Dumontet Charles C
Haematologica 20150130 5
Similar Datasets
Project description:Background: The clinical course of relapsed or refractory (r/r) diffuse large B-cell lymphoma (DLBCL) is variable, with limited efficacy data of second-line treatment in a post-rituximab real-world context. Hence, we explored the predictors and constructed a nomogram for risk stratification in this population. Patients and methods: Among 296 r/r DLBCL patients pretreated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) at the Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College between 2006 and 2017, 231 were included for nomogram construction. After randomization, we constructed the prognostic nomogram in the primary cohort (n=161) based on a multivariate analysis and confirmed it in the validation cohort (n=70). Additionally, we explored predictive factors for second-line therapy using a ordinal regression analysis. Results: Four independent prognostic factors including rituximab in the second-line setting, initial Eastern Cooperative Oncology Group (ECOG) performance status (PS), response to front-line treatment, and invasion on progression/recurrence were used to construct the nomogram. The nomogram had a C index of 0.70 with AUC values of 0.73 and 0.71 for the primary and validation cohorts, respectively. Subsequently, three risk groups (low, intermediate, and high) were determined with median overall survival (OS) of 38.0, 25.0, and 7.0 months, respectively. Additionally, we conducted a multivariate ordinal regression analysis and identified prior response to front-line treatment (odds ratio=4.50, 95% CI: 1.84-11.27, p=0.001) and bulky disease at diagnosis (odds ratio=0.36, 95% CI: 0.182-0.702, p=0.003) were two independent factors for second-line treatment efficacy. Conclusions: The established predictors for treatment efficacy and the novel nomogram for survival in r/r DLBCL patients could potentially be applied for risk stratification and treatment guidance in the post-rituximab era.
| S-EPMC6995391 | biostudies-literature
Project description:Although rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment for patients with diffuse large B-cell lymphoma (DLBCL), ?30% to 50% of patients are not cured by this treatment, depending on disease stage or prognostic index. Among patients for whom R-CHOP therapy fails, 20% suffer from primary refractory disease (progress during or right after treatment) whereas 30% relapse after achieving complete remission (CR). Currently, there is no good definition enabling us to identify these 2 groups upon diagnosis. Most of the refractory patients exhibit double-hit lymphoma (MYC-BCL2 rearrangement) or double-protein-expression lymphoma (MYC-BCL2 hyperexpression) which have a more aggressive clinical picture. New strategies are currently being explored to obtain better CR rates and fewer relapses. Although young relapsing patients are treated with high-dose therapy followed by autologous transplant, there is an unmet need for better salvage regimens in this setting. To prevent relapse, maintenance therapy with immunomodulatory agents such as lenalidomide is currently undergoing investigation. New drugs will most likely be introduced over the next few years and will probably be different for relapsing and refractory patients.
| S-EPMC6142522 | biostudies-literature
Project description:BackgroundOur study measured the body composition of Diffuse large B-cell lymphoma (DLBCL) patients receiving rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) regimen by computed tomographic (CT) and assessed their correlation with treatment-related toxicity and other adverse outcomes.MethodsWe retrospectively analyzed 201 DLBCL patients who underwent pre-treatment abdominal CT examination. CT images were used to assess body composition metrics at the third lumbar vertebrae including fat tissues and muscle. Based on the skeletal muscle area (SMA) and density (SMD), skeletal muscle index (SMI), skeletal muscle gauge (SMG = SMI × SMD) and lean body mass (LBM) were calculated. Also analyzed were the toxicity, adverse events and survival.ResultsWe found that SMG, SMD, SMI and LBM were correlated with any grade 3-4 toxicity, dose reduction, hospitalization or termination of the treatment due to immunochemotherapy and worse survival. However, multivariate analysis demonstrated SMG [progression-free survival (PFS): hazard ratio (HR), 2.889; 95% CI, 1.401-5.959; p = 0.004; overall survival (OS): HR, 2.655; 95% CI, 1.218-5.787; p = 0.014] was the best predictor of poor prognosis.ConclusionsSMG, SMD, SMI and LBM were identified as predictors of adverse reactions and poor survival. SMG was an innovative and valuable indicator of immunochemotherapy toxicity and other adverse outcomes. Additionally, it can be used to individualize antineoplastic drug dosing.
| S-EPMC8025815 | biostudies-literature
Project description:BACKGROUND:Rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) is used as standard frontline regimen for diffuse large B-cell lymphoma (DLBCL). The landscape of somatic mutations in DLBCL revealed that inactivation of EP300 plays an important role in lymphomagenesis. A common EP300 single nucleotide polymorphism (SNP) rs20551 results in the substitution of valine for isoleucine at codon 997 close to the Bromodomain. However, the association between SNP rs20551 and clinical prognosis in DLBCL patients treated with R-CHOP is unknown. METHODS:In this study we analyzed the EP300 SNP rs20551 and prognosis of 226 DLBCL patients who treated with R-CHOP or R-CHOP-like regimes from 2002 to 2013. Determination of the EP300 SNP rs20551 from genomic DNA was obtained by Sanger chain termination sequencing. RESULT:In this study, the frequency of the A and G allele of the EP300 SNP rs20551 in 226 patients were 92.5 and 7.5%, respectively. We did not observe obvious correlation between patients' disease features and the EP300 SNP rs20551. But the patients with genotype AA had a higher 5-year overall survival rate than those with genotype GA (77.0% vs. 64.7%, p = 0.045). Furthermore, multivariate Cox regression analysis showed that the GA genotype of EP300 SNP rs20551 was an independent poor prognostic factor for DLBCL patients treated with Rituximab-chemotherapy (p = 0.009, HR 2.956, 95% CI 1.315-6.645). CONCLUSION:This study suggests that EP300 SNP rs20551 might be a useful biomarker to predict the long-term outcome of R-CHOP in DLBCL patients.
| S-EPMC5513029 | biostudies-literature
Project description:Background/Aims: Hodgkin Lymphoma (HL) has become one of the most treatable cancers, with more than 80% patients in the advanced stage being cured through improvement of therapeutic regimens. Nevertheless, some treatments were accompanied with toxicities. Methods: In the current study, a network meta-analysis (NMA) was conducted to compare the efficacies and toxicities of different chemotherapy regimens for advanced Hodgkin lymphoma (HL). We reviewed PubMed and EMBASE databases from inception to May 2018, and identified randomized controlled trials (RCTs) in which advanced HL patients received chemotherapy. Fourteen eligible RCTs published between 1992 and 2017 were enrolled in this NMA. These studies included a total of 5,964 HL patients, and assessed at least one of seven different chemotherapy regimens. Direct and indirect evidence was combined to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs), and to establish a surface under the cumulative ranking (SUCRA) curve. Results: A cluster analysis was performed to evaluate efficacies and toxicities of different regimens. The COPP + ABVD (cyclophosphamide + vincristine + procarbazine + prednisone + doxorubicin + bleomycin + vinblastine + dacarbazine) regimen had the highest SUCRA partial response and overall remission rate values, while the ABVD regimen resulted in the lowest incidences of anemia, thrombocytopenia, neutropenia, and leucopenia. Conclusion: Cluster analysis revealed that COPP + ABVD had the best efficacy against advanced HL among the seven regimens, and ABVD had the lowest toxicity.
| S-EPMC8635017 | biostudies-literature
Project description:As a widely recognized standard regimen, R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) is able to cure two-thirds patients with diffuse large B cell lymphoma (DLBCL), and the remaining patients suffer from refractory or relapsed disease due to resistance to R-CHOP and fare poorly. Unsatisfied outcomes for those relapsed/refractory patients prompted efforts to discover new treatment approaches for DLBCL, including chimeric antigen receptor T cells, bispecific T cell engagers, immunomodulatory drugs, immune checkpoint inhibitors, monoclonal antibodies, antibody-drug conjugates, molecular pathway inhibitors, and epigenetic-modifying drugs. Herein, up-to-date data about the most promising treatment approaches for DLBCL are recapitulated, and novel genetic classification systems are introduced to guide individualized treatment for DLBCL.
| S-EPMC7734862 | biostudies-literature
Project description:Activated B-cell-like (ABC) diffuse large B-cell lymphoma (DLBCL), the major constituent of nongerminal center B-cell-like (non-GCB) DLBCL, is associated with poorer survival outcomes than GCB-type DLBCL. In Phase II studies, lenalidomide combined with R-CHOP (R(2)-CHOP) improved outcomes relative to historical R-CHOP in newly diagnosed DLBCL, particularly in non-GCB cases. ROBUST (CC-5013-DLC-002) is a randomized, double-blind, global, Phase III study of oral lenalidomide (15 mg, days 1-14) plus R-CHOP21 × 6 versus placebo-R-CHOP21 × 6 in patients with previously untreated ABC-type DLBCL. Subtyping is done within 3 calendar days by central laboratory gene-expression profiling of formalin-fixed paraffin-embedded biopsy tissue. The primary end point is progression-free survival. Secondary end points include response rates, overall survival and health-related quality of life.
| S-EPMC5551933 | biostudies-literature
Project description:We identified multiple single nucleotide variants (SNVs) in the TP53 3' untranslated region (3'UTR) in tumor specimens from 244 patients with diffuse large B-cell lymphoma (DLBCL). Patients carrying a wild-type TP53 coding sequence (CDS) and 1 or more 3'UTR SNVs had a better 5-year survival rate than patients carrying a wild-type CDS and the reference 3'UTR, yet there is no statistically significance difference in overall survival (OS). In contrast, 3'UTR variation predicted poorer OS for patients with a mutant TP53 CDS. We then sequenced TP53 3'UTR in 247 additional DLBCL patients as a validation set. Altogether, we identified 187 novel SNVs; 36 occurred at least twice. Most of the newly identified 3'UTR SNVs were located at sites that are complementary to seed sequences of microRNAs (miRNAs) that are predicted or experimentally known to target TP53. Three SNVs disrupt the seed match between miR-125b and the TP53 3'UTR, thereby impeding suppression of p53 by this miRNA. In addition, a germline SNV (rs78378222) located in the TP53 polyadenylation signal resulted in downregulation of both p53 messenger RNA and protein levels and reduction of cellular apoptosis. This study is the first to demonstrate the prognostic value of the TP53 3'UTR in cancer.
| S-EPMC3668486 | biostudies-literature
Project description:BackgroundR-CHOP has significantly improved survival rates of patients with diffuse large B cell lymphoma (DLBCL) by ~20% as compared to CHOP. CD20 antigen, highly expressed on more than 80% of B-cell lymphomas, is the target for rituximab. The goal of our study was to examine polymorphism in the CD20 gene in Chinese DLBCL population and whether CD20 gene polymorphism is associated with clinical response to R-CHOP.MethodCD20 gene polymorphism was detected in the entire coding regions including 6 exons by polymerase chain reaction (PCR)-sequencing assay in 164 patients with DLBCL. Among them, 129 patients treated with R-CHOP as frontline therapy (R ≥ 4 cycles) were assessable for the efficacy.ResultsPolymorphisms at three single nucleotides (SNP) were identified in the entire coding regions of the CD20 gene in the 164 patients. One of them, CD20 Exon2 [216] was found to be highly correlated with response to R-CHOP. Patients with homozygous C genotype showed a trend toward higher overall response rate than others with CT plus TT genotype (90.6% vs. 79.5%; P =0.166). A trend toward higher complete remission (CR) rate was observed in patients with homozygous C genotype (67.4%) compared with CT plus TT genotype (47.1%) (P = 0.091).ConclusionThese results suggest that there are 3 SNPs in CDS of the CD20 gene in Chinese DLBCL population. The CC genotype at Exon2 [216] appears to be associated with favourable response to R-CHOP.
| S-EPMC3686705 | biostudies-literature
Project description: Not available
| S-EPMC8499090 | biostudies-literature