The impact of diagnostic wait time on the survival of patients with diffuse large B‐cell lymphoma: effect modification by the International Prognostic Index

Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non–germinal center B-cell–like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m2 intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP ( P = .611). Two-year PFS rates were 77.6% with R-CHOP and 82.0% with VR-CHOP; they were 65.1% versus 72.4% in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade ≥ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.

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No Benefit from Rituximab Containing Regimens in Patients with Primary Extranodal Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood.v112.11.3615.3615 ◽

2008 ◽

Vol 112 (11) ◽

pp. 3615-3615

Author(s):

Gonzalo Gutiérrez-García ◽

Luis Colomo ◽

Neus Villamor ◽

Leonor Arenillas ◽

Antonio Martínez ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Primary Cns Lymphoma ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Cns Lymphoma ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

Abstract Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous category of lymphoid tumors that comprises different clinical forms not fully recognized in the WHO classification. In this regard, extranodal (EN) DLBCLs have particular clinicobiological features and outcome, sometimes related to the specific site where the lymphoma arises. Nowadays, rituximab plus chemotherapy (CT) is the gold-standard in the treatment of DLBCL. However, the superiority of rituximab-CT (R-CT) over CT alone has not been addressed for all the clinical subsets of the disease and, in fact, the clinical role of the new therapies might be different for primary nodal or EN DLBCLs. The aim of this study was to assess the impact of rituximab in patients suffering from nodal or EN DLBCL. Two-hundred and thirty non-immunocompromised patients (112M/118F; median age, 61 years) diagnosed with CD20+DLBCL in a single institution between 1997 and 2006 (five years before and after establishing R-CT as the standard treatment in DLBCL) and treated with adriamycin-containing regimens were the subject of the present study. The series included 148 primary nodal and 82 EN DLBCL. Patients with primary CNS lymphoma were excluded and lymphomas arising at Waldeyer ring were considered as nodal DLBCL. The main EN sites were GI (n=26), bone (n=13), soft tissue (n=13), lung/pleura (n=9), liver (n=9), and other (n=12). Main clinico-biological and evolutive variables were analyzed. One hundred nineteen patients received only CT and 111 R-CT. Eighty-seven cases with available information were assigned to germinal center B-cell-like (GCB) (41%) or non-GCB (59%) groups according to the Hans method (Blood2004;103:275–82) based on CD10, BCL6 and MUM1 expression. Main initial features, including the primary nodal or EN origin, international prognostic index (IPI), and GCB/non-GCB categories were similar for CT and R-CT groups. No correlation was observed between the GCB/non-GCB groups and the primary site of the tumor, although nodal lymphomas more frequently expressed MUM1 than EN (69% vs. 31%, respectively; p=0.01). CR rate and 5-year overall survival (OS) according to the treatment arm (CT vs. R-CT) is detailed for the whole series and for the nodal and EN groups in the table and OS curves depicted in the figure. In the whole series, variables predicting poor OS in the multivariate analysis were high-risk IPI (RR 2.5; p<0.001), primary nodal involvement (RR 1.6; p=0.04) and no R-CT treatment (RR 1.9; p=0.002). In the nodal group, IPI and no R-CT maintained the prognostic value, whereas in the primary EN only IPI predicted OS. Moreover, no difference in OS was observed according to the nodal or EN origin in those patients receiving R-CT. Biological subtypes GCB vs. non-GCB did not add predictive information neither in the whole series nor in the nodal or EN groups. In conclusion, patients with primary EN DLBCL seem to have little benefit from the use of R-CT. Nevertheless, this intriguing observation should be confirmed in further prospective studies. Complete response CR (%) 5-years OS (%) CT R-CT CT R-CT *p<0.002 R-CT vs. CT All cases (n=230) 59 79* 46 70* Primary nodal (n=148) 54 78* 34 71* Primary extranodal (n=82) 68 78 70 69 Figure Figure

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Immunohistochemical Expression of Germinal Center and Non-Germinal Center Markers in Primary Gastric Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood.v112.11.5276.5276 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5276-5276

Author(s):

Fernando Hurtado ◽

Brady Beltran ◽

Luis Riva ◽

Renzo Salas ◽

Domingo Morales ◽

...

Keyword(s):

B Cell ◽

Germinal Center ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Immunohistochemical Expression ◽

Large B Cell Lymphoma ◽

The Impact ◽

Large B Cell

Abstract BACKGROUND: Recent studies have shown a correlation between diffuse large B-cell lymphoma (DLCBL) prognosis and molecular features using genome profiles by cDNA microarrays. Later reports have shown that immunohistochemical tests using markers as CD10, bcl-6 and MUM-1 to identify germinal center B-cell (GCB) and non-GCB patterns can have a similar value and are gaining major importance in assessing prognosis in patients with DLBCL. Gastric DLCBL is the most frequent extranodal non-Hodgkin lymphoma. AIM: To evaluate the frequency of GCB and non-GCB subgroups in primary gastric DLCBL and the impact of these tests in prognosis. PATIENTS AND METHODS: Patients older than 18 years with a diagnosis of primary gastric DLBCL were identified in a single institution from January 2002 to December 2005 and included in this analysis. Immunohistochemical stains were performed using antibodies against CD20, CD10, bcl-6 and MUM1 in all cases. Survival curves were obtained using the Kaplan-Meier method. RESULTS: Twenty-nine patients were included in this study. The median age at diagnosis was 68 years (range 40 to 86 years). Thirteen male and 16 female patients were included. All cases received chemotherapy with CHOP regimen. Cases were subclassified in GCB and non-GCB using CD10, bcl-6, and MUM1 expression. Four cases (14%) were considered GCB and 25 cases (86%) non-GCB. There were no statistical differences between both groups in the following variables: age, ECOG performance status, serum LDH levels, clinical stage and International Prognostic Index (IPI) score. No statistical difference in survival was observed between the GCB and non-GCB groups. The 3-year overall survival for the entire group was 30%. CONCLUSION: Immunohistochemical expression of non-GCB pattern is very frequent in primary gastric DLBCL in Peru. However, it does not show an effect in survival, probably related to the small number of cases included in the present study.

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Identification of a Patient Cohort with Relapsing Diffuse Large B-Cell Lymphoma with a Low International Prognostic Index in PET/CT Using a 2-Gene (LMO2/TNFRSF9) Scoring System

Acta Haematologica ◽

10.1159/000505605 ◽

2020 ◽

Vol 143 (6) ◽

pp. 600-602

Author(s):

Nader Omidvar ◽

Nilgun Tekin ◽

Paulette Conget ◽

Flavia Bruna ◽

Botond Timar ◽

...

Keyword(s):

B Cell ◽

Scoring System ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Patient Cohort ◽

Large B Cell Lymphoma ◽

Pet Ct ◽

Large B Cell

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Circulating long non-coding RNAs HOTAIR, Linc-p21, GAS5 and XIST expression profiles in diffuse large B-cell lymphoma: association with R-CHOP responsiveness

Scientific Reports ◽

10.1038/s41598-021-81715-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Mahmoud A. Senousy ◽

Aya M. El-Abd ◽

Raafat R. Abdel-Malek ◽

Sherine M. Rizk

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Expression Profiles ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Diagnostic Tools ◽

Large B Cell Lymphoma ◽

Non Coding Rnas ◽

Large B Cell

AbstractThe reliable identification of diffuse large B-cell lymphoma (DLBCL)-specific targets owns huge implications for its diagnosis and treatment. Long non-coding RNAs (lncRNAs) are implicated in DLBCL pathogenesis; however, circulating DLBCL-related lncRNAs are barely investigated. We investigated plasma lncRNAs; HOTAIR, Linc-p21, GAS5 and XIST as biomarkers for DLBCL diagnosis and responsiveness to R-CHOP therapy. Eighty-four DLBCL patients and thirty-three healthy controls were included. Only plasma HOTAIR, XIST and GAS5 were differentially expressed in DLBCL patients compared to controls. Pretreatment plasma HOTAIR was higher, whereas GAS5 was lower in non-responders than responders to R-CHOP. Plasma GAS5 demonstrated superior diagnostic accuracy (AUC = 0.97) whereas a panel of HOTAIR + GAS5 superiorly discriminated responders from non-responders by ROC analysis. In multivariate analysis, HOTAIR was an independent predictor of non-response. Among patients, plasma HOTAIR, Linc-p21 and XIST were correlated. Plasma GAS5 negatively correlated with International Prognostic Index, whereas HOTAIR positively correlated with performance status, denoting their prognostic potential. We constructed the lncRNAs-related protein–protein interaction networks linked to drug response via bioinformatics analysis. In conclusion, we introduce plasma HOTAIR, GAS5 and XIST as potential non-invasive diagnostic tools for DLBCL, and pretreatment HOTAIR and GAS5 as candidates for evaluating therapy response, with HOTAIR as a predictor of R-CHOP failure. We provide novel surrogates for future predictive studies in personalized medicine.

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Concurrent Expression of MYC and BCL2 in Diffuse Large B-Cell Lymphoma Treated With Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone

Journal of Clinical Oncology ◽

10.1200/jco.2011.41.0985 ◽

2012 ◽

Vol 30 (28) ◽

pp. 3452-3459 ◽

Cited By ~ 556

Author(s):

Nathalie A. Johnson ◽

Graham W. Slack ◽

Kerry J. Savage ◽

Joseph M. Connors ◽

Susana Ben-Neriah ◽

...

Keyword(s):

Protein Expression ◽

B Cell ◽

Cell Lymphoma ◽

Molecular Subtype ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Bcl2 Protein ◽

Large B Cell

Purpose Diffuse large B-cell lymphoma (DLBCL) is curable in 60% of patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). MYC translocations, with or without BCL2 translocations, have been associated with inferior survival in DLBCL. We investigated whether expression of MYC protein, with or without BCL2 protein expression, could risk-stratify patients at diagnosis. Patients and Methods We determined the correlation between presence of MYC and BCL2 proteins by immunohistochemistry (IHC) with survival in two independent cohorts of patients with DLBCL treated with R-CHOP. We further determined if MYC protein expression correlated with high MYC mRNA and/or presence of MYC translocation. Results In the training cohort (n = 167), MYC and BCL2 proteins were detected in 29% and 44% of patients, respectively. Concurrent expression (MYC positive/BCL2 positive) was present in 21% of patients. MYC protein correlated with presence of high MYC mRNA and MYC translocation (both P < .001), but the latter was less frequent (both 11%). MYC protein expression was only associated with inferior overall and progression-free survival when BCL2 protein was coexpressed (P < .001). Importantly, the poor prognostic effect of MYC positive/BCL2 positive was validated in an independent cohort of 140 patients with DLBCL and remained significant (P < .05) after adjusting for presence of high-risk features in a multivariable model that included elevated international prognostic index score, activated B-cell molecular subtype, and presence of concurrent MYC and BCL2 translocations. Conclusion Assessment of MYC and BCL2 expression by IHC represents a robust, rapid, and inexpensive approach to risk-stratify patients with DLBCL at diagnosis.

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Diffuse large B-cell lymphoma: A single-institution experience of patient outcomes.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.7_suppl.271 ◽

2016 ◽

Vol 34 (7_suppl) ◽

pp. 271-271

Author(s):

Ryan James Chan ◽

Rasna Gupta ◽

Sindu Mary Kanjeekal ◽

Mohammed Jarrar ◽

Amin Kay ◽

...

Keyword(s):

British Columbia ◽

B Cell ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

B Cell Lymphoma ◽

Canadian Province ◽

Large B Cell Lymphoma ◽

Cancer Program ◽

Large B Cell

271 Background: The Windsor Regional Cancer Program (WRCP) was determined to have consistently been a top performer in time to treatment of diffuse large B cell lymphoma in this Canadian province (http://www.csqi.on.ca/by_type_of_cancer/lymphoma/lymphoma_treatment/). We endeavored to determine whether faster time to diagnosis and treatment for diffuse large B-cell lymphoma (DLBCL) influenced the IPI score (International Prognostic Score), thereby predicting an improved clinical outcome in these presenting patients. Methods: The WRCP services a catchment area of 650,000 people. A retrospective chart review was conducted for patients diagnosed with DLBCL at the Windsor Regional Cancer Program (WRCP) between 2006-2012. Information collected included the five factors for scoring by the International Prognostic Index (IPI) – age, performance status, LDH, stage, and number of extranodal sites – chemotherapy regimen, relapses, existence of second malignancies, cause of death, and dates of diagnosis, last follow-up, and death. We analyzed the relationship between prognostic factors and these clinical outcomes, and also compared the IPI scores for this cohort of patients against a similar population in another Canadian province, British Columbia. Results: It is established that compared to other cancer centres in Ontario, the WRCP is consistently reporting a shorter diagnosis to treatment metric when compared to their counterparts in Ontario, Canada. When compared to historical Canadian data, presenting IPI scores for DLBCL patients were lower on average for patients treated at the WRCP than those reported in British Columbia, Canada by Sehn et al. [Sehn, L. H., et al. (2007). The revised International Prognostic Index is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood, 109(5), 1857-1861.]. Conclusions: A lower presenting IPI score is known to be correlated improved lymphoma related outcome. With attention to the metric of diagnosis to treatment < 30 days for diffuse large B cell lymphoma, we expect an improved lymphoma related outcome for our patients. We recommend ongoing attention to this metric, in order to improve outcomes for our patients.

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