Event free survival at 24 months: A new endpoint in diffuse large B-cell lymphoma

Abstract Introduction Despite the advances in Diffuse Large B-Cell Lymphoma (DLBCL) treatment, there is a lack of uniformity regarding survival among the entire patient population. This study investigates several individual-level markers of socioeconomic and clinical status in relation to DLBCL survival. Methods This is a retrospective cohort study that utilizes a study population that was derived from the Moffitt Cancer Center Total Cancer Care protocol, a database that contains clinical, biological, and demographic information for over 73,000 patients as well as molecular and cytogenetic information on over 36,000 tumors. The database included 440 persons who were diagnosed with Diffuse Large B-Cell Lymphoma between 1998 and 2012. Of these persons, 274 met the eligibility criteria. A descriptive analysis was first conducted on all variables in the study and was then stratified by insurance status. A forward step-wise Cox proportional hazard regression was performed to calculate adjusted hazard ratios (HR) and their 95% confidence intervals for the association between insurance status and relapse, progression, or death utilizing SAS 9.3 (SAS Institute, Inc., Cary, NC). The Kaplan-Meier method was used to generate survival curves for each insurance group and compared according to the log-rank test. This was done in order to examine any differences in median survival time (in months) between the two groups. Results In terms of both overall survival and event-free survival, race was a significant prognostic factor in this study with non-Caucasian subjects being more likely to experience mortality (HR 2.33; 95% CI, 1.39 - 3.88). Subjects who presented with b-symptoms (fevers, unintentional weight loss >10%, and night sweats) at the time of diagnosis were significantly more likely to experience mortality (HR 2.48; 95% CI, 1.67 - 3.67) than those who were without them. Both stage and nodal status of a subject’s disease at the time of diagnosis were significantly associated with the outcome as subject’s with advanced stage disease (HR 3.89; 95% CI, 2.25 - 6.76) and extra nodal disease (HR 1.58; 95% CI, 1.04 - 2.39) had a higher risk of death. For overall survival, subjects in the privately-insured group experienced a significant difference in overall survival time (Log-Rank p=0.04) compared to those subjects with government-subsidized insurance (Figure 1). There was also a statistically significant difference in event-free survival between the two insurance groups (Log-Rank p=0.05) (Figure 2). Notably, age was not a significant covariate for OS or EFS, suggesting that the government-subsidized group was not biased by an increased proportion of elderly Medicare enrolled patients. Discussion In this retrospective cohort study, we observed that event-free survival time among subjects with private insurance were significantly improved from those subjects with government-subsidized insurance and overall survival time among subjects with private insurance were significantly improved from those subjects with government-subsidized insurance. We determined that after adjustment for demographic and clinical covariates, the covariates race, presentation of b-symptoms at the time of diagnosis, stage at the time of diagnosis, and nodal status of a subject’s disease were all significant prognostic factors in both overall and event-free survival. Disclosures: No relevant conflicts of interest to declare.

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Ofatumumab Versus Rituximab Salvage Chemoimmunotherapy in Relapsed or Refractory Diffuse Large B-Cell Lymphoma: The ORCHARRD Study

Journal of Clinical Oncology ◽

10.1200/jco.2016.69.0198 ◽

2017 ◽

Vol 35 (5) ◽

pp. 544-551 ◽

Cited By ~ 64

Author(s):

Gustaaf W. van Imhoff ◽

Andrew McMillan ◽

Matthew J. Matasar ◽

John Radford ◽

Kirit M. Ardeshna ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Salvage Treatment ◽

Event Free Survival ◽

First Line ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell

Purpose We compared the efficacy of ofatumumab (O) versus rituximab (R) in combination with cisplatin, cytarabine, and dexamethasone (DHAP) salvage treatment, followed by autologous stem-cell transplantation (ASCT) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Patients and Methods Patients with CD20+ DLBCL age ≥ 18 years who had experienced their first relapse or who were refractory to first-line R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)–like treatment were randomly assigned between three cycles of R-DHAP or O-DHAP. Either O 1,000 mg or R 375 mg/m2 was administered for a total of four infusions (days 1 and 8 of cycle 1; day 1 of cycles 2 and 3 of DHAP). Patients who experienced a response after two cycles of treatment received the third cycle, followed by high-dose therapy and ASCT. Primary end point was progression-free survival (PFS), with failure to achieve a response after cycle 2 included as an event. Results Between March 2010 and December 2013, 447 patients were randomly assigned. Median age was 57 years (range, 18 to 83 years); 17% were age ≥ 65 years; 63% had stage III and IV disease; 71% did not achieve complete response (CR) or experience response for < 1 year on first-line R-CHOP. Response rate for O-DHAP was 38% (CR, 15%) versus 42% (CR, 22%) for R-DHAP. ASCT on protocol was completed by 74 patients (33%) in the O arm and 83 patients (37%) in the R arm. PFS, event-free survival, and overall survival were not significantly different between O-DHAP versus R-DHAP: PFS at 2 years was 24% versus 26% (hazard ratio [HR], 1.12; 95% CI, 0.89 to 1.42; P = .33); event-free survival at 2 years was 16% versus 18% (HR, 1.10; P = .35); and overall survival at 2 years was 41% versus 38% (HR, 0.90; P = .38). Positron emission tomography negativity before ASCT was highly predictive for superior outcome. Conclusion No difference in efficacy was found between O-DHAP and R-DHAP as salvage treatment of relapsed or refractory DLBCL.

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Lack of Prognostic Significance of Pretreatment Total Metabolic Tumor Volume on Event-free Survival at 24 Months in Diffuse Large B-cell Lymphoma

10.33696/haematology.1.003 ◽

2020 ◽

Vol 1 (1) ◽

Keyword(s):

B Cell ◽

Tumor Volume ◽

Cell Lymphoma ◽

Prognostic Significance ◽

B Cell Lymphoma ◽

Metabolic Tumor Volume ◽

Event Free Survival ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell

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Single Nucleotide Polymorphisms (SNPs) of FCγRIIA and FCγRIIIA in Patients with Diffuse Large B-Cell Lymphoma Have No Impact On Treatment Outcome of Elderly Patients with Diffuse Large B-Cell Lymphoma (DLBCL) Treated with CHOP with and without Rituximab: Results From the RICOVER-60 Trial of the German High-Grade Non-Hodgkin Lymhoma Study Group (DSHNHL).

Blood ◽

10.1182/blood.v114.22.3956.3956 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3956-3956

Author(s):

Manfred Ahlgrimm ◽

Evi Regitz ◽

Klaus-Dieter Preuss ◽

Sandra Grass ◽

Viola Poeschel ◽

...

Keyword(s):

Overall Survival ◽

Elderly Patients ◽

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Event Free Survival ◽

Free Survival ◽

Fisher Test ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Abstract 3956 Poster Board III-892 BACKGROUND During the last decade the outcome of patients with diffuse large B-cell lymphoma (DLBCL) has significantly improved by the addition of rituximab (R) to the standard chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). Despite this improvement in response rates, event- progression and overall survival, about one third of the patients with DLBCL will eventually fail. The main therapeutic efficacy of rituximab is not fully elucidated. One major effector mechanism is by antibody dependent cellular cytotoxicity (ADCC) mediated by cell-bound rituximab via its FCg part that activates effector cells by binding to their Fcg receptor (FCγR). Three classes and eight subclasses of FCγR have been described. SNPs have been detected for FcgRIIA at amino acid position (AA) 131 where histidin is substituted by arginin (131 R/H) and for FCγRIIIA at position 158, where phenylalanine is substituted by valine (158 V/F). These SNPs have an increased affinity to Fcg and induce a stronger ADCC which explains better responses to rituximab treatment in follicular lymphoma. The aim of this study was to determine the impact of FCγRIIA and FCγRIIIA SNPs on the outcome R-CHOP chemotherapy in elderly patients with newly diagnosed DLBCL. PATIENTS AND METHODS In the RICOVER-60 therapy study 1222 elderly patients (aged 61-80 years) were randomly assigned to 6 or 8 cycles of CHOP, both with or without rituximab (Pfreundschuh et al., Lancet Oncology 2008). The control group (n=100) consisted of anonymous healthy blood donors of Saarland University Institute of Transfusion Medicine. Available for this study were peripheral blood samples from 570 patients who were representative for the entire RICOVER-60 population. The 2 FCgR SNPs FCγ-RIIa AA 131 R/H and FCγ-RIIIa 158 V/F were determined and univariate and multivariate analyses adjusting for the IPI-relevant risk factors (LDH, ECOG performance status, advanced stage and >1 extranodal involvement) were performed for the entire study population and separately for patients receiving or not receiving rituximab. RESULTS Frequencies of FCγ-RIIa and FCγ-RIIIa polymorphisms were not different in healthy controls compared to DLBCL patients. In our statistical analyses finaly 512 patients were included. The characteristic for the groups were for group 1 (6x CHOP-14) 127 patients (24.8%), for group 2 (8x CHOP-14) 122 patients (23.83%), for group 3 (6x CHOP-14+8x rituximab) 124 patients (24.22%) and for group 4 (8x CHOP-14 + 8x rituximab) 139 patients (27.15%) [fisher test (included vs excluded): p=0.4691]. The median age at admission was the same for included and excluded patients. The gender characteristics for the included patients were well balanced [fisher test (included vs excluded): p=1.0000]. The median observation time for the included vs. excluded patients was 40.25 months vs. 34.50 months. This verification shows that the collective of included patients represents the whole RICOVER-60 population. Statistical analyses of overall survival, 3 year event-free survival and 3 year overall-survival were done for the complete RICOVER-60 population. 3-year event-free survival was 47.2% after six cycles of CHOP-14 (95% CI 41.2-53.3), 53.0% (47.0-59.1) after eight cycles of CHOP-14, 66.5% (60.9-72.0) after six cycles of R-CHOP-14, and 63.1% (57.4-68.8) after eight cycles of R-CHOP-14. 3-year overall survival was 67.7% (62.0-73.5) for six cycles of CHOP-14, 66.0% (60.1-71.9) for eight cycles of CHOP-14, 78.1% (73.2-83.0) for six cycles of R-CHOP-14, and 72.5% (67.1-77.9) for eight cycles of R-CHOP-14. Compared with treatment with six cycles of CHOP-14, overall survival improved by -1.7% (-10.0-6.6) after eight cycles of CHOP-14, 10.4% (2.8-18.0) after six cycles of R-CHOP-14, and 4.8% (-3.1-12.7) after eight cycles of R-CHOP-14. In summary, event-free, progression free, overall survival and complete remission rates were not different among patients with FCγ-RIIa (AA 131R/H) and FCγ-RIIIa (AA 158 V/F) SNPs, irrespective of whether the entire RICOVER-60 population was analysed or when patients treated with and without rituximab were analysed separately. CONCLUSIONS FCγ-RIIa and FCγ-RIIIa SNPs have no influence on the outcome of patients treated with CHOP-14 with or without rituximab. Therefore, modifications of schedule and dose of rituximab according to the underlying FCγ-R SNPs are not justified. Supported by a HOMFOR grant of Saarland University Medical School, Homburg, Germany Disclosures: Pfreundschuh: Roche MabThera Advisory Board: Consultancy, Honoraria.

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Outcome and pathologic classification of children and adolescents with mediastinal large B-cell lymphoma treated with FAB/LMB96 mature B-NHL therapy

Blood ◽

10.1182/blood-2012-04-422709 ◽

2013 ◽

Vol 121 (2) ◽

pp. 278-285 ◽

Cited By ~ 51

Author(s):

Mary Gerrard ◽

Ian M. Waxman ◽

Richard Sposto ◽

Anne Auperin ◽

Sherrie L. Perkins ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Stage Iii ◽

Event Free Survival ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Pathologic Classification ◽

Adolescent Patients ◽

Large B Cell

Abstract Mediastinal large B-cell lymphoma (MLBL) represents 2% of mature B-cell non-Hodgkin lymphoma in patients ≤ 18 years of age. We analyzed data from childhood and adolescent patients with stage III MLBL (n = 42) and non-MLBL DLBCL (n = 69) treated with Group B therapy in the French-American-British/Lymphome Malins de Burkitt (FAB/LMB) 96 study. MLBL patients had a male/female 26/16; median age, 15.7 years (range, 12.5-19.7); and LDH < 2 versus ≥ 2 × the upper limit of normal, 23:19. Six MLBL patients (14%) had < a 20% response to initial COP (cyclophosphamide, vincristine, and prednisone) therapy. Central pathology revealed approximately 50% with classical features of primary MLBL. Five-year event-free survival for the stage III MLBL and non-MLBL DLBCL groups was 66% (95% confidence interval [CI], 49%-78%) and 85% (95% CI, 71%-92%), respectively (P < .001; 14%). The 5-year overall survival in the 42 MLBL patients was 73% (95% CI, 56%-84%). We conclude that MLBL in adolescent patients is associated with significantly inferior event-free survival compared with stage III non-MLBL DLBCL and can be of multiple histologies. Alternate treatment strategies should be investigated in the future taking into account both adult MLBL approaches and more recent biologic findings in adult MLBL.

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Personalized risk prediction for event-free survival at 24 months in patients with diffuse large B-cell lymphoma

American Journal of Hematology ◽

10.1002/ajh.24223 ◽

2015 ◽

Vol 91 (2) ◽

pp. 179-184 ◽

Cited By ~ 21

Author(s):

Matthew J. Maurer ◽

Jean-Philippe Jais ◽

Hervé Ghesquières ◽

Thomas E. Witzig ◽

Fangxin Hong ◽

...

Keyword(s):

B Cell ◽

Risk Prediction ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Event Free Survival ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Personalized Risk ◽

Large B Cell

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Association of expression of pSTAT3, pAKT1 with the survival of patients with diffuse large B-cell lymphoma

Kazan medical journal ◽

10.17816/kmj2020-501 ◽

2020 ◽

Vol 101 (4) ◽

pp. 501-506

Author(s):

E V Vaneeva ◽

V A Rosin ◽

D A Dyakonov ◽

S V Samarina

Keyword(s):

B Cell ◽

Tumor Cells ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

High Expression ◽

Event Free Survival ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

Low Expression

Aim. To assess the relationship between isolated and combined expression of pSTAT3, pACT1 in tumor cells with the survival of patients with diffuse large B-cell lymphoma (DLBCL). Methods. The study included 100 patients with the first diagnosed diffuse large B-cell lymphoma, observed in the institute's clinic between 2010 and 2018 who received standard first-line R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy. The relative number of expressing pSTAT3 and pAKT1 tumor cells was determined by using immunohistochemical and morphometric methods. The optimal cut-off level of expression on tumor cells estimated by using receiver operating characteristic (ROC) curve analysis for pSTAT3 was 68% and for pACT1 70%. Given these values, all patients with DLBCL were divided into groups with a high and low degree of expression of the biomarkers. As a result, 53 patients were enrolled in the pSTAT3 high expression group (68% tumor cells) and 47 patients to the pSTAT3 low expression group (68% tumor cells). Spearmans correlation coefficient was used to examine relationships. Overall survival and event-free survival were estimated by KaplanMeier curves. The log-rank test was used for groups comparison. Results. The five-year overall survival rate in the pSTAT3 high expression group was 55% versus 87% in the low expression group, p=0.015. A significant difference was found in the assessment of event-free survival: 43% for the group of pSTAT3 high expression, 66% for the group of low expression, p=0.011. A statistically significant value of a high level of pACT1 expression was revealed for 5-year overall and event-free survival (p 0.001 and p=0.003). Overall survival rate was 81% for the pACT1 low expression group and 43% for the high expression group while event-free survival rate was 64 and 41%, respectively. Also, patients with рАКТ1+/рSTAT3+ (high level) co-expression had extremely low rates of overall and event-free survival rates compared with the рАКТ1/рSTAT3 (low level) group (p=0.001; p 0.001). Conclusion. The pSTAT3 and pAKT1 biomarkers can be used as additional prognosis criteria for diffuse large B-cell lymphoma.

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Response Assessment after an Inductive CHOP or CHOP-Like Regimen with or without Rituximab in 103 Patients with Diffuse Large B-Cell Lymphoma (DLBCL): Integrating 18Fluorodeoxyglucose Positron Emission Tomography (PET) to the International Workshop Criteria (IWC).

Blood ◽

10.1182/blood.v108.11.2735.2735 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2735-2735

Author(s):

Jehan Dupuis ◽

Emmanuel Itti ◽

Alain Rahmouni ◽

Jean-Didier Rain ◽

Christian Gisselbrecht ◽

...

Keyword(s):

B Cell ◽

Clin Oncol ◽

Cell Lymphoma ◽

International Workshop ◽

B Cell Lymphoma ◽

Event Free Survival ◽

Free Survival ◽

Cox Regression Analysis ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background : 18Fluorodeoxyglucose-PET has been advocated as a powerful mean to evaluate response in aggressive non-Hodgkin’s lymphoma. Its relative merits compared to the widely accepted International Workshop Criteria (IWC) (Cheson, 1999. J Clin Oncol 17: 1244) have been investigated (Juweid, 2005 J Clin Oncol 23:4652), but need to be further confirmed. Materials and methods : We studied 103 patients with diffuse large B-cell lymphoma after 4 cycles of inductive CHOP or CHOP-like chemotherapy, with (n=51) or without Rituximab (n=52) using the IWC criteria and PET. The patients where also evaluated with an early PET after 2 courses, the results of which did not influence treatment decisions. PET response criteria have already been published (Haioun, Blood2005; 106). The interpretation of PET took into account the results of the early PET, in particular to define progressive disease. Results : The baseline characteristics of the patients where as follows : Median age 53y (19–78); age >60 : 25 (24%); LDH > normal : 71 (69%); > 1 extranodal site : 53 (51%); poor performance status (>=2) : 37 (36%); stage III–IV: 84 (81%). The international prognostic index (IPI) score was 0–2 in 40 pts (39%) and 3–5 in 63 (61%). The comparative response evaluation using IWC criteria or the combination of IWC criteria and PET is shown in the following table. Three years after completion of therapy, patients being in CR by PET at 4 cycles had an estimated event-free survival (EFS) of 83% if in CR/CRu by IWC criteria, and of 80% if in PR or SD by IWC. Patients not in CR by PET had an EFS of 51% when in CR/CRu by IWC criteria and of 8% when in PR, SD or PD by IWC criteria (p<0.0001 as compared to CR patients). The same differences were seen whether the patients had received Rituximab or not. In a multivariate Cox regression analysis, event free survival was adversely affected by a non-CR response after 4 cycles evaluated by PET (p<0.0001, relative risk (RR) = 8.3), but not by a poor IPI (3–5) (p = 0.6, RR = 0.81) or Rituximab-based treatment (p = 0.74, RR = 1.13). Conclusion : We confirm the higher predictive power of PET as compared to IWC criteria. The CRu category disappears from evaluation criteria when integrating informations delivered by PET, and PR patients can be separated into CR versus PR patients. The predictive value of PET is seen in patients treated with, as well as without Rituximab. IWC + PET Response CR CRu PR SD PD Total * 4 pts showed progression between 2 and 4 cycles on the basis of PET** 2 pts had no PET at 4 cycles because of early progression IWC CR 23 0 1 0 0 24 CRu 43 0 8 0 2 53 PR 9 0 3 0 2 14 SD 1 0 0 0 1 2 PD 0 0 1 0 5 6* Total 76 0 13 0 10 101**

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