scholarly journals Event-Free Survival at 24 Months Is a Robust End Point for Disease-Related Outcome in Diffuse Large B-Cell Lymphoma Treated With Immunochemotherapy

2014 ◽  
Vol 32 (10) ◽  
pp. 1066-1073 ◽  
Author(s):  
Matthew J. Maurer ◽  
Hervé Ghesquières ◽  
Jean-Philippe Jais ◽  
Thomas E. Witzig ◽  
Corinne Haioun ◽  
...  
Keyword(s):  
Overall Survival ◽  
General Population ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Population Data ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Age And Sex

Purpose Studies of diffuse large B-cell lymphoma (DLBCL) are typically evaluated by using a time-to-event approach with relapse, re-treatment, and death commonly used as the events. We evaluated the timing and type of events in newly diagnosed DLBCL and compared patient outcome with reference population data. Patients and Methods Patients with newly diagnosed DLBCL treated with immunochemotherapy were prospectively enrolled onto the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource (MER) and the North Central Cancer Treatment Group NCCTG-N0489 clinical trial from 2002 to 2009. Patient outcomes were evaluated at diagnosis and in the subsets of patients achieving event-free status at 12 months (EFS12) and 24 months (EFS24) from diagnosis. Overall survival was compared with age- and sex-matched population data. Results were replicated in an external validation cohort from the Groupe d'Etude des Lymphomes de l'Adulte (GELA) Lymphome Non Hodgkinien 2003 (LNH2003) program and a registry based in Lyon, France. Results In all, 767 patients with newly diagnosed DLBCL who had a median age of 63 years were enrolled onto the MER and NCCTG studies. At a median follow-up of 60 months (range, 8 to 116 months), 299 patients had an event and 210 patients had died. Patients achieving EFS24 had an overall survival equivalent to that of the age- and sex-matched general population (standardized mortality ratio [SMR], 1.18; P = .25). This result was confirmed in 820 patients from the GELA study and registry in Lyon (SMR, 1.09; P = .71). Simulation studies showed that EFS24 has comparable power to continuous EFS when evaluating clinical trials in DLBCL. Conclusion Patients with DLBCL who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. EFS24 will be useful in patient counseling and should be considered as an end point for future studies of newly diagnosed DLBCL.

Newly Diagnosed Diffuse Large B-Cell Lymphoma Patients Treated with Immunochemotherapy Who Are Alive and Progression Free 12 Months After Diagnosis Have a Subsequent Overall Survival Similar to That of the General Population

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1540-1540 ◽  
Author(s):  
Matthew J Maurer ◽  
Herve Ghesquieres ◽  
Thomas E. Witzig ◽  
Carrie A. Thompson ◽  
Ivana N. Micallef ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
General Population ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Age And Sex

Abstract Abstract 1540 Background: Diffuse Large B-cell Lymphoma (DLBCL) is the most common lymphoma in the western world. Outcomes have improved with the standard initial therapy of rituximab and anthracyline based chemotherapy (immunochemotherapy). However, 20–40% of patients will either fail to achieve remission or relapse following initial immunochemotherapy. Most relapses occur early, and long-term outcome of relapsed/refractory patients is generally poor despite salvage regimens and stem cell transplant. Traditionally, studies for DLBCL have been evaluated using progression-free and/or overall survival. However, the event rate in DLBCL slows significantly approximately 12–18 months after diagnosis, and late events are often due to competing (non-DLBCL related) risks, especially in older patients. Here we examine outcome of DLBCL patients based on their event status at 12 months. Methods: Newly diagnosed DLBCL patients were prospectively enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER). Clinical data were abstracted from medical records using a standard protocol. Patients were actively followed for events (progression, re-treatment, or death due to any cause) and overall survival (OS). Event-free status at 12 months after diagnosis (EFS12) was assessed as a dichotomous variable. Cause of death was determined by medical record and death certificate review using prospectively determined definitions. Expected survival was based on age and sex matched survival using the Minnesota population death rates. Confirmation cohorts were from a Lyon, France hospital based registry and NCCTG clinical trial N0489. Results: 680 patients with newly diagnosed DLBCL and treated with rituximab + anthracycline based chemotherapy were enrolled in the MER from 2002 to 2009. The median age was 62 years (range 18–92). 53% were male. At a median follow-up of 59 months (range 8–116), 266 patients (39%) had an event and 188 patients (28%) died. 162 patients (24%) had an event in the first 12 months after diagnosis, comprising 60% of all events. Patients with an event in the first 12 months had poor survival with death almost exclusively due to disease (Figures 1a, 2a). In contrast, patients who were event-free at 12 months had comparable survival to the age and sex matched general population (Figure 2b) and were more likely to die of other causes than DLBCL (Figure 1b). Overall survival rates by EFS12 status were validated in patients from a French hospital-based registry (N=265) and the NCCTG N0489 clinical trial (N=87) with additional replication studies underway. Conclusions: DLBCL patients who are event-free at 12 months after diagnosis have an excellent prognosis with an overall survival similar to that of an age- and sex- matched general population and are more likely to die of other causes than DLBCL. This finding has implications for clinical management, new clinical trials, and follow-up testing in this patient population. In contrast, patients with an event within the first 12 months after diagnosis have a poor prognosis with almost all deaths secondary to DLBCL. EFS status at 12 months identifies patients with poor outcomes due to disease. This can be utilized as an endpoint in biologic studies and clinical trials to address early treatment failures. EFS status at 12 months should be incorporated into prognostic models to identify high risk patients in newly diagnosed DLBCL. Disclosures: No relevant conflicts of interest to declare.

Genetic Polymorphisms In Genes Involved In R-CHOP Metabolism and Event-Free and Overall Survival In Diffuse Large B-Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 996-996 ◽  
Author(s):  
James R Cerhan ◽  
Thomas M Habermann ◽  
Matthew J Maurer ◽  
James E Wooldridge ◽  
Stephen M Ansell ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Variant Allele ◽  
Newly Diagnosed ◽  
Enzyme Expression ◽  
Large B Cell Lymphoma ◽  
Individual Snps ◽  
Large B Cell

Abstract Abstract 996 Background: Treatment with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has improved survival in diffuse large B-cell lymphoma (DLBCL) lymphoma, although a significant percentage of patients do not achieve a remission or they relapse. One potential explanation for this observation is that host pharmacogenetic background may impact metabolism, detoxification and transport of R-CHOP. However, there are few prospectively collected data that address pharmacogenetics in DLBCL, particularly for event-free and overall survival in the rituximab era. We therefore tested the hypothesis that functional candidate single nucleotide polymorphisms (SNPs) from genes involved in the metabolism of CHOP (CYP2C19, CYP3A5, ABCB1, ABCC2, ABCG2, RAC2, CYBA, NR3C1, GSTA1, GSTP1, TP53) and rituximab (FCGR2A, FCGR3A) influence prognosis in DLBCL. Methods: We genotyped 19 SNPs from 13 genes in a prospective cohort of newly diagnosed DLBCL patients with germline DNA enrolled at the Mayo Clinic and University of Iowa from 2002–2008 as part of the Molecular Epidemiology Resource of the Iowa/Mayo Lymphoma SPORE. All patients were systematically followed through 2009 for overall survival (OS) and event-free survival (EFS), defined as disease progression, retreatment or death due to any cause. All SNPs were genotyped on the Illumina Golden-Gate platform. Cox regression was used to estimate Hazard Ratios (HRs) and 95% confidence intervals (CI) for individual SNPs with OS and EFS. Each SNP was modeled with the most prevalent homozygous genotype used as the reference group. An ordinal test was used to assess the trend across genotypes, and a p<0.05 was considered statistically significant. All Cox models adjusted for International Prognostic Index (IPI) and treatment. Results: The median age at diagnosis of the 439 DLBCL patients was 62 years (range 18–92). The IPI was distributed as follows: 0–1 (34%), 2 (26%), 3 (24%) and 4–5 (16%). All patients were treated with chemotherapy, and 91% received R-CHOP. Through 2009, there were 171 events (39%) and 122 (28%) deaths, with a median follow-up for living patients of 49 months (range 1–98). The SNP rs1045642 in the ATP-binding cassette (ABC) protein gene ABCB1 was associated with OS (p=0.012). The variant T allele for ABCB1 rs1045642 (minor allele frequency (MAF)=0.47) is associated with a silent I→I substitution, and the T allele predicts low enzyme expression. Compared to CC homozygotes, patients with CT (HR=0.66, 95% CI 0.44–0.99) or TT (HR=0.53, 95% CI 0.31–0.90) genotypes had superior OS. We also observed an association of the GSTP1 SNP rs1695 with OS (p-trend=0.018). The variant G allele (MAF of 0.31) is associated with an A→V substitution, and this change predicts low enzyme expression. Compared to AA homozygotes, patients with the AG (HR=0.78, 95% CI 0.54–1.14) or GG (HR=0.39, 95% CI 0.17–0.90) genotypes had superior OS. Nearly identical associations for these two SNPS were observed with EFS. There were no significant associations with any of the other SNPs that we evaluated. Conclusions: In a large series of newly diagnosed DLBCL patients treated in the rituximab era, we found evidence that genetic variation in ABCB1 and GSTP1 is associated with improved OS and EFS after adjusting for IPI and treatment. The variant allele for ABCB1 is associated with slower enzyme activity, favorably impacting doxorubicin and vincristine pharmacodynamics, and the variant allele for GSTP1 is associated with slower detoxification of doxorubicin and vincristine, increasing bioavailability of these drugs. A comprehensive evaluation of the role of pharmacogenetics in DLBCL is warranted. Support: P50 CA97274, R01 CA129539. Disclosures: No relevant conflicts of interest to declare.

Rituximab Does Not Improve Progression Free (PFS) or Overall Survival (OS) in Patients with Limited Stage Diffuse Large B Cell Lymphoma (DLBCL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3755-3755
Author(s):  
Ephraim P. Hochberg ◽  
Nicole Birrer ◽  
Christiana E. Toomey ◽  
Jeffrey A. Barnes ◽  
Alfred Ian Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Newly Diagnosed ◽  
Logrank Test ◽  
Limited Stage ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Abstract 3755 Poster Board III-691 Introduction Diffuse Large B Cell Lymphoma (DLBCL) is the most common lymphoid malignancy accounting for approximately 33% of all newly diagnosed NHLs. Three randomized trials and multiple retrospective analyses have demonstrated both progression-free (PFS) and overall survival (OS) benefit to the addition of the anti-CD20 monoclonal antibody rituximab to anthracycline-containing chemotherapy in older advanced-stage patients, and in young low-risk patients with DLBCL. Approximately half of newly diagnosed patients with DLBCL present in limited stage and the benefit of rituximab containing chemotherapy regimens for these patients remains uncertain. Methods We used an IRB-approved clinicopathologic database, derived from comprehensive tumor registry data at the Massachusetts General Hospital, Dana Farber Cancer Institute and Brigham and Women's Hospital, to identify all patients 18 years or older diagnosed with limited stage DLBCL between 2000 and 2006. We included all patients treated with 3 or more cycles of anthracycline containing chemotherapy with curative intent. We excluded primary DLBCL of the CNS. We determined the impact of the use of rituximab on OS and PFS. PFS and OS were calculated from the date of initial diagnosis. Results A total of 138 patients met eligibility criteria and are included in the analysis. Median age was 51 years (range 18-89 years). 30% of patients were above 60 years of age, and less than 3% had an IPI score of 3 or higher. One hundred and six patients received CHOP + rituximab (RCHOP) and 32 received CHOP alone. Of the 106 patients receiving RCHOP, 48 were irradiated and 58 were not. Of the 32 patients receiving CHOP, 20 received radiation and 12 did not. At a median follow-up of 35 months (range 3-109 months), PFS and OS for the entire cohort are 86.2% and 90.6%, respectively. On univariate analysis of outcome, the addition of rituximab to CHOP did not improve PFS (81.3% vs. 87.7%,p=0.817, Logrank Test) or OS (84.4% vs. 92.5%, p=0.411, Logrank Test). Conclusion The outcome of an unselected series of patients with limited stage DLBCL is excellent. In this retrospective cohort of patients with limited stage DLBCL, the use of rituximab in conjunction with standard chemotherapy did not improve PFS or OS. The results we obtained are very similar to those reported by SWOG (Persky et al. JCO 2008). The overlapping confidence intervals for PFS and OS between SWOG 0014 and 8736 patients and our data suggest that a large multicenter trial will be needed to show a benefit of rituxan in this extremely good prognosis population. Disclosures: Hochberg: Genentech: Speakers Bureau; Biogen-Idec: Speakers Bureau; Enzon: Speakers Bureau; Amgen: Speakers Bureau.

scholarly journals Primary Cutaneous Diffuse Large B Cell Lymphoma -Leg Type in United States: Epidemiology and Survival Outcome

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2202-2202
Author(s):  
Lubina Arjyal ◽  
Megha Giri ◽  
Dipesh Uprety ◽  
Yazhini Vallatharasu ◽  
Swapna Talluri ◽  
...  
Keyword(s):  
Overall Survival ◽  
General Population ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Survival Outcome ◽  
Younger Patients ◽  
Large B Cell Lymphoma ◽  
Large B Cell ◽  
Cutaneous B Cell Lymphoma

Background: Primary cutaneous diffuse large B cell lymphoma-leg type (DLBCL-LT) is relatively uncommon lymphoma accounting for about 1 to 3 % of all cutaneous lymphoma and about 10-20% of primary cutaneous B cell lymphomas. There is data for survival outcomes in primary cutaneous B cell lymphoma in general population after introduction of rituximab but little is known about outcomes in DLBCL-LT patients in general population. The available data on survival in DLBCL-LT are from small case series and single institution studies. We conducted this study to evaluate the survival outcome in patients with PCDLBCL-LT after introduction of rituximab. Methods: We utilized SEER 18 database to select adult (18+ years) patients diagnosed from 2004 to 2014 with ICD-3-0 code of 9680/3 (diffuse large B cell lymphoma, not otherwise specified)with localized stage by summary stage 2000 with skin as the primary site of disease to identify patient with DLBCL-LT. Patients were divided into various cohorts based on age (<65 versus 65+ years), sex, race (Caucasians, African American and Others) and median household income of county of residence (< $50,00 versus ≥ $50,000). We utilized SEER*stat to calculate age adjusted incidence rate using 2000 US standard population. Kaplan Meyer curve was utilized to calculate 5-year overall survival. Cox proportional hazard model was used for multivariate analysis of factor associated with survival. Result: A total of 485 patients were identified with DLBCL-LT as the only or first primary cancer case. The median age at diagnosis was 70 years. Its incidence was found to be about 0.09 case per 100,000 population with incidence in males being about 1.6 times that of females. Majority of patient included in our study were males (52 %), older (59.4%), and Caucasians (85.6%). 5-year overall survival was found to be 59%. Older patients were found to have significantly worse 5-year overall survival compared to younger patients with HR of 7.9 with 95% CI of 4.9 to 12.7. There was no disparity in cancer outcome based on race, sex or median income of the county of residence. When we compared the outcome of patients diagnosed in earlier 5 years to later 6 years of the study period, the survival curves almost overlapped suggesting that there has been little if any improvement in outcome in recent years. Conclusion: Our study showed that about 60% of patients with DLBCL-LT live for 5 years in real world setting which is comparable to the outcome reported by other studies on outcome in primary cutaneous B cell lymphoma. Even though this is disease of elderly, as the median age at diagnosis is 70 years, the outcome in older population was found to be significantly worse compared to younger patients. Given this is relatively uncommon disease, we recommend large registry-based studies to try to improve outcome in these patient population. Disclosures No relevant conflicts of interest to declare.

scholarly journals Cell of origin in diffuse large B-cell lymphoma in systemic lupus erythematosus: molecular and clinical factors associated with survival

2019 ◽  
Vol 6 (1) ◽  
pp. e000324 ◽  
Author(s):  
Basile Tessier-Cloutier ◽  
David DW Twa ◽  
Eva Baecklund ◽  
Randy Gascoyne ◽  
Nathalie A Johnson ◽  
...  
Keyword(s):  
Overall Survival ◽  
General Population ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Of Origin ◽  
Large B Cell Lymphoma ◽  
Extranodal Disease ◽  
Bcl2 Protein ◽  
Large B Cell

BackgroundSLE is associated with increased risk of diffuse large B-cell lymphoma (DLBCL). DLBCL is routinely classified by cell of origin (COO), with germinal centre B-cell (GCB) being more common and indicating better prognosis in the general population. We studied COO subtyping in patients with SLE diagnosed with DLBCL and their survival.Patients and methodsWe evaluated 20 cases of SLE with DLBCL. Immunohistochemistry analysis was performed (BCL2, MYC, BCL6, CD10, CD20, FOXP1, GCET1, MUM1) in tissue microarrays. We examined associations between molecular and clinical features, including overall survival.ResultsOf the 20 DLBCL SLE cases, 12/20 cases (60%) were classified as non-GCB using Hans or Choi algorithms. MYC and BCL2 protein expression was positive in 6/20 (30%) and 8/20 (40%) SLE cases, respectively, with 2/20 (10%) co-expressing both markers. Seven (7/20) had only extranodal involvement at DLBCL diagnosis. As expected, non-GCB cases had worse survival. Cases presenting exclusively with extranodal disease were associated with shorter SLE duration and better survival despite higher BCL2 protein expression.ConclusionsWe present novel data characterising DLBCL in SLE. Sixty per cent of the DLBCL in patients with SLE were non-GCB. The nodal and extranodal distribution in SLE was similar to what is known in the general population, but extranodal disease occurred more often with short SLE duration and was associated with longer overall survival. More research on cancer in SLE is the key to further understanding the complex interplay between cancer and the immune system.

Absolute Monocyte Count At Diagnosis Is a Poor Prognostic Factor and Impacts Survival in Diffuse Large B-Cell Lymphoma: A Collaborative Multi-Center Study Involving 1026 Patients.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2651-2651
Author(s):  
Tamar Tadmor ◽  
Bari Alessia ◽  
Stefano Sacchi ◽  
Luigi Marcheselli ◽  
Eliana Valentina Liardo ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Peripheral Blood Monocyte ◽  
Monocyte Count ◽  
Newly Diagnosed ◽  
Non Hodgkin Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 2651 In non-Hodgkin lymphoma (NHL), individual characteristics of the tumor cells alone are not the only parameters which determine prognosis and overall survival. Non-malignant immune cells and the tumor microenvironment also play an important contributory role in determining the eventual clinical outcome. There is an increasingly growing interest in the role of monocytes and their precursors in the pathogenesis of lymphoproliferative disorders. Recently, elevated peripheral blood monocyte counts have been shown to be an independent prognostic parameter associated with poor prognosis and decreased overall survival in patients with both non- Hodgkin lymphoma and Hodgkin. The main aim of this collaborative multicenter study was to re-evaluate and attempt to verify the prognostic significance of monocytosis (> 800 cells/mm3) at diagnosis, in a large cohort of 1026 newly diagnosed patients with diffuse large B-cell lymphoma (DLBCL) followed at different medical centers both in Israel and Italy. Additional aims of this study were to define possible correlations with a number of other well recognized prognostic factors in DLBCL. We reviewed clinical and laboratory data of consecutive untreated patients with DLBCL, followed and eventually treated in different centers in Haifa, Israel and in Italy between 1993–2010. Median age at diagnosis was 59 years (range 18–95 yrs) and the 5-years OS after a median follow up of 51 months (range 0.2–180 months) was 69% for the entire cohort. Monocyte counts were available for 852 patients. Those with peripheral blood monocyte count (PBMC) < 800 mm3 had a 5 years OS of 71%, compared to 59% for those with PBMC > 800 mm3 (p=0.0002). In univariate analysis age, IPI score and monocyte counts were associated with a worse OS. In multivariate analysis, monocytosis retained a negative prognostic value even when adjusted for IPI (HR 1.53, CI95% 1.16–2.02, p=0.003). Of the 852 patients, 496 (58%) were treated with chemotherapy alone, while 356 patients (42%) received chemo-immunotherapy with similar regimens including rituximab. The addition of rituximab to the combination chemotherapy did not abrogate the negative adverse effect of monocytosis (p=0.0015) observed in patients receiving chemotherapy alone. This large validation study confirms earlier very recent results and shows that the monocyte level (monocytosis), a simple prognostic parameter, can easily be used routinely to evaluate newly diagnosed patients with DLBCL and identify those with a higher risk of poor survival. The addition of monocytosis as an additional parameter to the basic IPI, may possibly generate a more comprehensive score incorporating both patient, tumor and immune parameters. Disclosures: No relevant conflicts of interest to declare.

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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