scholarly journals Shorter Diagnosis-to-Treatment Interval in Diffuse Large B-Cell Lymphoma is Associated With Inferior Overall Survival in a Large, Population-Based Registry

2021 ◽  
Vol 19 (6) ◽  
pp. 719-725
Author(s):  
Danielle N. Blunt ◽  
Liam Smyth ◽  
Chenthila Nagamuthu ◽  
Evgenia Gatov ◽  
Ruth Croxford ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Treatment Initiation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Time Dependent ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Background: Because of prolonged screening requirements, patient and time-dependent selection have been proposed as potential biases in clinical trials. The screening process may exclude patients with a need for emergent treatment (and a short period from diagnosis to treatment initiation [DTI]). We explored the impact of DTI on overall survival (OS) in a population-based cohort of patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods: Using population-based administrative databases in Ontario, Canada, we identified adults aged ≥18 years with DLBCL treated with rituximab-based chemotherapy for curative intent between January 2005 and December 2015. Cox regression and multivariable analyses were presented to evaluate the impact of time from DTI on OS, controlling for relevant covariates. Results: We identified 9,441 patients with DLBCL in Ontario; median age was 66 years, 53.6% were male, median number of comorbidities (Johns Hopkins aggregated diagnosis groups) was 10 (interquartile range [IQR], 8–13), and median DTI was 37 days (IQR, 22–61). Between treatment initiation and study end, 43% of patients died (median OS, 1 year; IQR, 0.4–2.8 years). Shorter DTI was a significant predictor of mortality (P<.001). Compared with the shortest DTI period of 0–18 days, those who commenced therapy at 19–29 days (hazard ratio [HR], 0.75; 95% CI, 0.68–0.84), 30–41 days (HR, 0.70; 95% CI, 0.63–0.78), 42–57 days (HR, 0.52; 95% CI, 0.46–0.58), and 58–180 days (HR, 0.52; 95% CI, 0.47–0.58) had improved survival. Increasing age (HR, 1.03; 95% CI, 1.03–1.04), male sex (HR, 1.23; 95% CI, 1.14–1.32), and increasing number of comorbidities (HR, 1.12; 95% CI, 1.11–1.13) were associated with inferior survival. Conclusions: Among patients with DLBCL, shorter DTI was associated with inferior OS. Therefore, DTI may represent a surrogate marker for aggressive biology. Clinical trials with lengthy screening periods are likely creating a time-dependent patient selection bias.

Outcome of Diffuse Large B Cell Lymphoma in the VA System: The Rituximab Era.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4729-4729
Author(s):  
Rami S. Komrokji ◽  
Sanjay Maraboyina ◽  
Rami Y. Haddad ◽  
Zeina A. Nahleh ◽  
Malek M. Safa
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Wilcoxon Test ◽  
P Value ◽  
Medical Centers ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Background: Addition of rituximab to chemotherapy in patients with diffuse large B cell Lymphoma (DLBCL) has been shown to improve survival in several recent clinical studies. A study from British Columbia confirmed those results in a population-based cohort. No similar population based studies were conducted in the USA. Our study aims to address outcome of DLBCL in the era of rituximab in the VA health system. Methods: This was a retrospective analysis. The VA Central Cancer Registry (VACCR) database was used to identify patients with DLBCL diagnosed between 1995 and 2005. There are approximately 120 VA medical centers diagnosing and/or treating patients with cancer. The VACCR aggregates the data collected by the medical centers’ cancer registries. Data were extrapolated and analyzed using bio-statistical software SPSS. Variables included age, sex, stage of disease, histology subtype, date of diagnosis, date of last contact, date of relapse, vital status, whether patients received chemotherapy and or radiation. Use of rituximab was not specifically recorded in the registry. Due to that we divided the patients into two groups, patients diagnosed with DLBCL before 2001 (pre rituximab era group) and patients diagnosed after 2001 (rituximab era group). The initial results of rituximab in DLBCL were presented in 2000 and published in January 2002. Independent t test was used for comparing continuous variables and chi square test for categorical variables. Wilcoxon test was used to compare survival among the two groups. Results: There were 2792 patients with DLBCL at the VACCR between 1995 and 2005, 1772 patients in pre rituximab era and 1020 patients in the rituximab era. The mean age at diagnosis was to 64 in pre rituximab group and 66 in rituximab group (P-value 0.015). Race distribution was similar between the two groups. More patients were diagnosed at advanced stage (stage III and IV) 61 % in rituximab group compared to 57% in pre rituximab group (P-value &lt;0.005), IPI score data were not available. More patients in pre rituximab era did not receive multi-agent chemotherapy 28% versus 22% (P-value &lt; 0.005). More patients received radiation 21 % in pre rituximab group compared to 16% in rituximab era group (P-value &lt; 0.005). The 5-year overall survival was 26% in pre rituximab era and 36% after rituximab (P-value 0.0025). Using Cox regression multivariable analysis age, use of mutli-agent chemotherapy, radiation and whether patients were diagnosed and treated before or after 2001 were statistically significant independent variables affecting survival. Conclusions: Overall survival of DLBCL in VA patients had improved in the rituximab era. The magnitude of improvement observed in this study is similar to what was described in previous studies. Other factors contributing to improvement in outcomes such as supportive care could not be differentiated in this study. This is a population-based study suggesting improvement in survival in DLBCL in the rituximab era.

The Impact of Activated Akt Expression On Clinical Outcome in Diffuse Large B-Cell Lymphoma: A Clinicopathological Study of 99 Cases.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2676-2676
Author(s):  
Jung Yong Hong ◽  
Moon Ki Choi ◽  
Young Saing Kim ◽  
Chi Hoon Maeng ◽  
Su Jin Lee ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Clinical Impact ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

Abstract Abstract 2676 Purpose Akt is a serine/threonine kinase that plays a central role in cell proliferation and growth. To define clinical impact of Akt expression in diffuse large B-cell lymphoma(DLBCL), we investigated the expression of phospho-Akt(p-Akt) in DLBCL and analyzed clinical impact of p-Akt expression on patient survival. Methods We evaluated the p-Akt expression in 99 DLBCL patients using tissue microarray(TMA) technology. Results Positive p-Akt expression was observed in 15.2% of the patients and significantly associated with elevated lactic dehydrogenase level (P = .044). Kaplan-Meier survival analysis showed that the patients with positive p-Akt expression showed substantially poorer overall survival (p-Akt+ vs p-Akt- 25.3 months [95% confidence interval(CI), 14.4–36.2 months] vs 192.6 months [95% CI, 131.3–253.9 months], P < .001) and progression-free survival (p-Akt+ vs p-Akt- 13.6 months[95% CI, 14.4–36.2 months] vs 134.5 months [95% CI, 131.3–253.9 months], P < .001), respectively. Multivariate Cox regression analysis revealed that patients with DLBCL with p-Akt positivity showed poorer overall survival with 3.2 fold (95% CI, 1.6–6.8, P = .002) risk for death compared to patients with DLBCL with p-Akt negativity. Conclusion Positive expression of p-Akt in DLBCL patients is associated with poorer overall and progression-free survival. Expression of p-Akt may act as an independent poor prognostic factor and might be a novel therapeutic target for DLBCL. 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 The impact of age on survival of diffuse large B-cell lymphoma – a population-based study

2014 ◽  
Vol 54 (6) ◽  
pp. 916-923 ◽  
Author(s):  
Gustaf Hedström ◽  
Oskar Hagberg ◽  
Mats Jerkeman ◽  
Gunilla Enblad ◽  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Population Based Study ◽  
Large B Cell Lymphoma ◽  
The Impact ◽  
Large B Cell

scholarly journals The Impact on Survival of EBV Positive Diffuse Large B- Cell Lymphoma, Not Otherwise Specified in Young Adults

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5407-5407
Author(s):  
Brady E. Beltrán ◽  
Denisse A. Castro ◽  
Julio Vega ◽  
Jose Manuel Malaga ◽  
Mauricio Postigo ◽  
...  
Keyword(s):  
Overall Survival ◽  
Young Adults ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Not Otherwise Specified ◽  
Large B Cell Lymphoma ◽  
Impact On Survival ◽  
The Impact ◽  
Large B Cell

Abstract Introduction: Epstein Barr virus-positive (EBV+) diffuse large B- cell lymphoma (DLBCL), not otherwise specified (NOS) is a new entity recognized by the WHO 2016. This entity was widely studied in older age patients, but in recent years there are few reports that show that EBV positive DLBCL, NOS can affect younger adults and there is a lack of evidence in this age group. The aim of this study is to evaluate the impact on survival in EBV+ DLBCL, NOS in young adults. Methods: The study was retrospective, reviewing clinical records of patients treated at Rebagliati Martins Hospital between years 2002 - 2013. Patients of both sexes ≥ 18 years old, but ≤ 50 years old, with the diagnosis of EBV+DLBCL, NOS were included. IRB approval was obtained prior to research. Pathological samples were reviewed by hematopathologists at our institution to confirm the diagnosis. Pertinent clinicopathological data were collected through chart review and are presented using descriptive statistics. Overall survival (OS) was determinate according to the Kaplan -Meier method, the comparison of the survival curves were made with the log-rank test. Univariate and multivariate Cox proportional-hazard regression models were fitted to evaluate hazard ratios (HR) for OS. Results: A total of 57 patients with a diagnosis of EBV+DLBCL, NOS were included in this analysis. The median age at diagnosis was 43 years (range 25-50 years), 61 % of patients were older than 40 years old and there was a slight female predominance (51%). Clinically, 55% presented ECOG >1, 57% had B symptoms, 68% had an extranodal disease as a primary tumor, 50% had stage III/IV and 26% had ≥ 1 extranodal site involved. EBV positivity was present in 16% of patients (9 patients). PDL-1 expression was present in 12% of patients. 92% received first-line treatment, but 7% of patients did not for progressive disease and death at diagnosis. During the treatment, 92% of patients received R-CHOP and 8% received other regimens. The overall response rate was 71%; 63% had a complete response and 7% had a partial response. The 5-year OS rate was 59%. In the univariate analysis, EBV positivity (<0.001) and ≥ 1 extranodal site involved (p=0.011) were associated with a poor prognosis. In the multivariate analysis, patients with EBV positive had a worse outcome (HR 7.8, 95% 2.2-25.9.2; p=0.001). Conclusions: The prevalence of EBV in young adults with DLBCL is high compared with other series and there is an adverse impact on overall survival in this group of patients. Figure. Figure. Disclosures Castillo: Genentech: Consultancy; Abbvie: Consultancy, Research Funding; Millennium: Research Funding; Beigene: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding.

Prognostic Importance of Comorbidity in a Population-Based Analysis of Patients with Advanced-Stage Diffuse Large B-Cell Lymphoma (DLBCL) Treated with R-CHOP

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3656-3656
Author(s):  
André Wieringa ◽  
Eric N. van Roon ◽  
Peter Joosten ◽  
Tim Beerden ◽  
Huib Storm ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Lymphoma ◽  
Significant Risk ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Ann Arbor ◽  
Population Based Registry ◽  
Large B Cell

Abstract Abstract 3656 Introduction Diffuse large B-cell lymphoma (DLBCL) is predominantly diagnosed in the elderly and its incidence is therefore rapidly increasing. Rituximab in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) is the standard treatment for patients with newly diagnosed DLBCL. This is mainly based on data from carefully controlled randomised trials with strict eligibility criteria. Therefore data reflecting the “real world” in the rituximab era are sparse. We conducted an observational prospective cohort study to identify whether comorbidity is an independent risk factor for overall survival (OS) in patients with newly diagnosed DLBCL treated with R-CHOP with curative intent. Methods All patients with newly diagnosed DLBCL in Friesland, a Dutch province, are prospectively registered by their clinicians in a population-based registry (HemoBase®) since January 2005. Patients ≥18 years, CD20 positive, Ann Arbor stage II-IV were included if they received ≥ one cycle of R-CHOP. Clinical variables registered were age, gender, performance status (PS), Ann Arbor stage, presence of B-symptoms, lactate dehydrogenase, bulky disease, number of extranodal sites involved. Comorbidity was scored using the Charlson Comorbidity Index (CCI) [Charlson et. al.; J Chron Dis, 1987]. The score is a summation of the number of comorbidities existing at the time of diagnosis. The group was divided in low CCI (0–1) and high CCI (≥2). The primary endpoint was OS, defined as start of diagnose of DLBCL until death by any cause. Cox Proportional hazards model was used to identify significant risk factors. Variables used to calculate International Prognostic Index (IPI) and CCI were entered into the model. Kaplan-Meier curves were evaluated by log-rank test. Results Over a period of 7 years 302 patients were newly diagnosed with DLBCL after the start of the HemoBase® registry. Of those patients, 76 received no R-CHOP therapy, 9 had unknown Ann Arbor stage and 61 had Ann Arbor stage I. Therefore data from 156 patients could be retrieved from the population-based registry for further analysis. The median age was 69 years (range 23 – 93). The median observation period for the total population was 24 months (range 0 – 83) and for patients still alive 33 months (range 2 – 83). Twenty-five percent of patients had a PS≥2, 39% had IPI≥3. The percentage of patients with 8, 7, 6, 5, 4, 3, 2, or 1 R-CHOP cycle(s) given were 49, 3, 32, 1, 3, 4, 2, 6 respectively. R-CHOP21 was given to 74% and R-CHOP14 to 26%. Dose reduction of 20% or more in doxorubicin, cyclophosphamide or vincristine occurred in 26, 19, and 36% of the patients respectively. In 54% of the patients dose reduction occurred in one or more antineoplastic drugs. Twenty-five patients had a CCI≥2. Most frequently observed comorbidities in the CCI≥2 group were diabetes (36%), peripheral vascular disease (32%), chronic pulmonary disease or second tumor (28%), myocardial infarction (24%), congestive heart failure or cerebrovascular disease (16%). The percentage of patients with a CCI score of 2, 3, 4 or 5 were 64, 28, 4 and 4% respectively. In the CCI≥2 group only 16% of the patients had also a PS≥2. Three year OS in the total study population was 68%: in patients with CCI<2 71% and in CCI≥2 48%. As shown in figure 1, the median overall survival was 18 months in the CCI≥2 group and over 80 months in CCI<2 (p=0.01). From multivariate analysis of CCI and IPI variables only CCI≥2 (p=0.01; HR 2.41 (95%CI 1.20 – 4.87) and PS≥2 (p<0.001; HR 3.77 (95%CI 1.91 – 7.45) were identified as significant risk factors for poor overall survival. Conclusion In this population-based analysis of all patients with advanced-stage DLBCL treated with R-CHOP in a Dutch cohort over a period of 7 years, comorbidity is an important and independent adverse risk factor. Comorbidity data provide important prognostic information on OS, thereby aiding patient consultation in daily practice. Furthermore, our results demonstrate the importance of population-based research. Disclosures: No relevant conflicts of interest to declare.

Relative Survival and Incidence Based Mortality of Diffuse Large B-Cell Lymphoma (DLBCL) in Rituximab Era: Population Based Study From Modena Cancer Registry (MCR)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5185-5185
Author(s):  
Luigi Marcheselli ◽  
Raffaella Marcheselli ◽  
Alessia Bari ◽  
Claudia Cirilli ◽  
Eliana Valentina Liardo ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Cell Lymphoma ◽  
Relative Survival ◽  
B Cell Lymphoma ◽  
Population Based ◽  
Male Gender ◽  
Population Based Study ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 5185 BACKGROUND. In the last 10 years retrospective studies and randomized clinical trial showed an improvement of survival in patients with Diffuse Large B Cell Lymphoma (DLBCL) and Follicular Lymphoma (FL) treated with chemotherapy regimens containing rituximab (R). However, clinical trials based data refer to a very selective subgroup of patients that does not necessarily correspond to the general population. Therefore we analysed data available from the cancer registry of the province of Modena (MCR), Italy, where R was introduced as standard treatment of DLBCL starting from 2003. Aim of this study was to evaluate if the survival benefit of R treatment observed in clinical trials in patients with DLBCL was confirmed in a study population METHODS. From 1996 to 2008 we identified 662 metachronous DLBCL (ICDO3 histology codes 9678–9680 6984/3) that were divided in two groups: 345 patients diagnosed between 1996 and 2002 (before the use of R), and 317 from 2003 to 2008 (when R was routinely used in the province of Modena). Relative survival (RS) was estimated using the Hakulinen method, with the complete cohort approach and age-adjusted by Corazziari method. The relative risks (RR) by gender and year of diagnosis (1996–2002 vs 2003–2008) was estimated assuming Poisson distribution for excess deaths. Moreover, by means of incidence based mortality approach (IBM) we estimated the overall effect of introduction of the R with the rate mortality ratio (RMR) between the cohort 2004–2007 (last follow-up 2008, N=198) and 1998–2001 (last follow-up 2002, N=200), and the effect by gender and age at diagnosis (<70 and ≥70 years old). Mortality data were extracted from MCR using the ICD9 codes 200 and 202. For all estimates we reported the confidence intervals at 95% (95%IC). RESULTS. The cohort consisted of 662 patients recorded in MCR in the period 1996–2008 (last data of follow-up is 31/12/2009) 51% of which were male and 47% ≥70 years old. The population of the province of Modena in 2008 was 677,896 (about 1.1% of Italian population). Overall, the RS in the period 2003–2008 and 1996–2002 was 61.0% (95%IC:53.8–67.9%) and 43.1% (95%IC: 37.0–49.1%), respectively (RR 0.63, P<0.001). The RS of male gender in 2003–2008 was 62.1% (95%IC: 51.6–71.8%) compared with 38.0% (95%CI: 29.8–46.6%) in the period 1996–2002 (RR=0.56, P<0.001); the RS for female was 58.7% (95%IC: 48.2–68.2%) in the period 2003–2008 and 48.1% (95%CI: 39.4–56.6%) in the period 1996–2002 (RR=0.71, P=0.047). Overall, from IBM analysis the RMR between period 2004–2008 vs 1998–2001 was 0.68 (95%CI: 0.50–0.94, P=0.018). From the same comparison for age <70, RMR was 0.56 (95%CI: 0.33–0.96, P=0.034) and for age ≥70 RMR was 0.74 (95%CI: 0.49–1.09, P=0.128). For male gender RMR was 0.71 (95%CI: 0.46–1.11, P=0.132) and for female was 0.65 (95%CI 0.41–1.03, P=0.068). CONCLUSIONS. This population based study includes exclusively patients with DLBCL, many of which would not have met the trial inclusion criteria, thus reflecting the experience of everyday clinical practice in a homogenous geographic area. Our results show an improvement in survival after the introduction of R for the treatment of DLBCL, that confirms the data from clinical trials and the population based study of LH Sehn (1). Furthermore, using IBM method the RMR highlighted an overall decrease of mortality in the “R period” compared to the period “before R”. This is particularly evident for patients younger than 70 and, with a minor effect, in the female gender. ACKNOWLEDGEMENTS: the study has been supported by “Associazione Angela Serra per la Ricerca sul Cancro”, Italy. Disclosures: No relevant conflicts of interest to declare.

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