Primary Splenic Diffuse Large B-Cell Lymphoma (PS-DLBCL): Splenectomy Improves Survival

Abstract Introduction: Although the spleen is involved in about a third of patients with non-Hodgkin's lymphoma (NHL), primary splenic diffuse large B-cell lymphoma (PS-DLBCL) is rare having a reported incidence of less than 1% of all NHL. Most of the described series include small numbers of patients before the rituximab era and the role of splenectomy treatment in addition to immuno-chemotherapy is unknown. Methods: Data were retrospectively collected for 87 patients (pts) with PS-DLBCL treated in 7 medical centers in Israel during the years 1982-2013. Patients presenting with systemic disease with splenic involvement or those having a diagnostic biopsy from other nodal or extranodal disease were excluded. Results: The mean age was 59.6 years (range, 24-89 years); 57.5% were male. Abdominal pain was reported in 61 pts (81%), B symptoms in 49 pts (59%), ECOG performance status 0 - 1 in 85%. Stage I disease was recorded in 28%, II in 33%, III in 18%, and IV in 21%. Thrombocytopenia (<100,000/µl) was recorded in only 6 pts. Lactic dehydrogenase levels (LDH) were elevated in 69 pts (84%). Favorable International Prognostic Index (IPI) 0-2 was recorded in 62 pts (72%). The mean splenic length was 17.34±6 cm (range 7- 37 cm) and the mean splenic weight was 1216 gm±1243 gm (range 180-6000 gm). A splenic mass was found in 97% of pts, and its mean size was 9.26 cm (range 3-18 cm). The diagnostic procedure was core needle biopsy in 46 pts and splenectomy in 39 pts: 27 underwent open splenectomy and 12 laparoscopic splenectomy. Splenectomized pts had lower IPI (p<0.05) and lower stage (p<0.05) compared to non-splenectomized pts. Treatment: The CHOP regimen was given to 80 pts (92%), DA-EPOCH was given to 2 pts (2%) and 5 pts (6%) received other regimens. Rituximab was given to 68 pts (78%). Complete response was achieved in 67 pts (80%) and partial response in 8 (9%). Relapse occurred in 17 pts (22%). Survival: The median follow-up time was 7 years (range 0-19.4 years). During this period 24 pts died (27.5%). The 5-year overall survival (OS) was 76.6±4.9% and 5-year event-free survival (EFS) 67.2±5.5%. Splenectomy at diagnosis improved survival: the 5-year EFS was 85.4±6% and 54.7±8% for splenectomized and non-splenectomized pts respectively (p=0.02) and the 5-year OS was 91.2±5% and 67.9±7% respectively (p=0.08). For the 53 pts with stage I-II disease, both 5-year EFS and OS were better in the splenectomized pts (p<0.02, Fig 1). The 5-year EFS and OS in pts with stage I and II disease that were splenectomized at diagnosis was 89.6±6% and 96.4±3.5% as compared with 50.5±11% and 63.2±11% in pts who were not splenectomized (p=0.012 and 0.009). The EFS and OS were not influenced by the stage of the disease. Overall survival was associated with B symptoms (p=0.02), weight loss (p=0.04) and ECOG performance status (p=0.03). In a multivariate model, low ECOG PS and splenectomy independently predicted a better EFS (p=0.03 and 0.02 respectively), however for OS, low ECOG PS independently predicted better OS (p=0.03), while splenectomy had only marginal effect on the OS (p=0.056). Conclusions: In our group of pts, PS-DLBCL generally presented with abdominal pain, high LDH and a splenic mass. We demonstrate for the first time that splenectomy at diagnosis improves survival in early stages of PS-DLBCL. Our study is a retrospective one. Therefore, until prospective studies prove that early splenectomy in PS-DLBCL is beneficial in terms of overall survival, the risk and benefit of performing splenectomy should be weighed for each patient. Fig 1: (A) Event-free survival and (B) Overall survival in patients with primary splenic DLBCL and stages I - II disease who did or did not undergo splenectomy at diagnosis. Fig 1:. (A) Event-free survival and (B) Overall survival in patients with primary splenic DLBCL and stages I - II disease who did or did not undergo splenectomy at diagnosis. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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Clinical Outcomes of R-CHOP Chemotherapy Alone Compared with R-CHOP Plus Radiotherapy in Patients with Localized, Non-Bulky Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood.v124.21.4421.4421 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4421-4421

Author(s):

Ji Hyun Park ◽

Dok Hyun Yoon ◽

Shin Kim ◽

Jung Sun Park ◽

Sang-wook Lee ◽

...

Keyword(s):

Overall Survival ◽

Clinical Outcomes ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

Event Free Survival ◽

Chop Chemotherapy ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Clinicopathologic Parameters

Abstract Introduction Although several previous studies addressed the role of radiation in treating localized diffuse large B-cell lymphoma (DLBCL), chemotherapy alone has shown promising efficacy with the emergence of Rituximab. Thus, we evaluated the clinical efficacy outcomes and failure patterns of patients with localized DLBCL according to two different treatment strategies, either 6 or more cycles of R-CHOP chemotherapy alone or 3 or 4 cycles of R-CHOP followed by involved field radiotherapy (IFRT). Methods A prospectively collected database from 21 tertiary centers participating the Consortium for Improving Survival of Lymphoma (CISL), built up for PROCESS study (NCT01202448) for secondary central nervous system involvement in DLBCL, was recruited for current study in addition to the Asan Medical Center (AMC) Lymphoma Registry. CISL database and AMC lymphoma registry consisted of data from patients with newly diagnosed DLBCL between August 2010 and August 2012, and between February 2004 and February 2012, respectively. Inclusion criteria were localized (stage I or II), non-bulky (<10cm in longest diameter) DLBCL treated with R-CHOP as 1st line chemotherapy, and patients either who received 6 or more cycles of R-CHOP chemotherapy only (R-CHOP alone group) or received 3 or 4 cycles of R-CHOP chemotherapy followed by IFRT (R-CHOP plus RT group). Comparisons of clinicopathologic parameters, clinical outcomes and the patterns of relapse were performed between two groups. The types of relapse were classified as either locoregional or distant, according to whether it involves any separate region from primary sites. Efficacy outcomes included complete response (CR) rate, 2-year overall survival (OS) rate, and 2-year event-free survival (EFS) rate. Results A total of 357 patients (CISL prospective cohort: 161 patients, AMC registry: 196 patients) were eligible for the analyses. Two hundred ninety nine patients (83.5%) received 6 or more cycles of R-CHOP chemotherapy alone, and 58 patients (16.2%) underwent 3 or 4 cycles of R-CHOP followed by IFRT. Median age was 54 years (range, 16-87). During the median follow-up of 24 months (range, 4-116 months), 35 patients (9.8%) experienced relapse, and 22 patients (6.1%) died. Two-year OS and EFS rate was 94.7% and 89.9%, respectively, and 345 out of 357 patients (96.6%) achieved CR. Comparing R-CHOP alone to R-CHOP plus RT group, there was no significant difference in clinicopathologic parameters. R-CHOP alone could achieve significantly higher CR rate of 97.7 % than 91.4% of R-CHOP plus RT group (p = 0.030). Two-year OS and EFS were significantly longer in R-CHOP alone group than R-CHOP plus RT group (96.1 vs 89.9 %, p = 0.029 and 91.7% vs 81.8%, p= 0.028) (Figure 1). Relapse rate was significantly lower in R-CHOP alone group compared with R-CHOP plus RT group than group (7.4% vs 22.4%, p=0.001), and distant relapses were also significantly lower (15.5% vs 2.7%, p<0.001). In addition, even only in relapsed patients, R-CHOP alone group showed lower incidence of distant relapses with marginal statistical significance (36.4% vs 69.2 %, p=0.062) (Table 1). Conclusion In our cohort, R-CHOP alone for six to eight cycles without IFRT could achieve significantly higher 2-year OS and EFS rate as well as CR compared with R-CHOP plus RT group. In addition, the rate of relapse and systemic failure were significantly lower in R-CHOP alone group, which altogether warrant further validation in prospective trial. Table 1. Explorative comparison of overall clinical outcomes and patterns of relapse between two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Total (%) R-CHOP alone group (%) R-CHOP plus RT group (%) P -value Number of patients 357 (100) 299 (83.5) 58 (16.2) Treatment response Complete response 345 (96.6) 292 (97.7) 53 (91.4) 0.030 Overall response 351 (98.3) 294 (98.3) 57 (98.3) 1.000 Rate of relapse 35 (9.8%) 14 (7.4) 11 (22.4) < 0.001 Median time to relapse (95% CI) 11 (7-15) 11 (8-14) 10 (5-14) 0.346 Pattern of relapse < 0.001 (0.062) Locoregional 14 (4.7) (63.6) 4 (6.9) (30.8) Distant 8 (2.7) (36.4) 9 (15.5) (69.2) Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 1. Comparison of overall survival and event-free survival in two subgroups: patients who underwent six or more cycles of R-CHOP chemotherapy alone and who underwent 3 or 4 cycles of R-CHOP followed by IFRT Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

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Clinical and Quality of Life Predictors of Failure to Achieve Event Free Survival at 24 Months in Patients Aged 70 Years and Older with Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood-2018-99-118356 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3579-3579

Author(s):

Patrick M. Reagan ◽

Andrea M Baran ◽

Matthew J. Maurer ◽

Andrew L. Feldman ◽

Thomas M. Habermann ◽

...

Keyword(s):

Research Funding ◽

B Cell Lymphoma ◽

Event Free Survival ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Treatment Data ◽

Study Population ◽

Pre Treatment ◽

Ecog Ps

Abstract Background Age has long been recognized as a poor prognostic factor in diffuse large B-cell lymphoma (DLBCL) and more recently, a lower baseline quality of life (QOL) in patients with aggressive lymphomas has been associated with an inferior overall survival (OS) (Thompson et al, 2018). Older patients with DLBCL are a heterogeneous population and commonly have comorbid conditions. A concerted effort to identify prognostic factors specific to this population is needed, including QOL. Event free survival at 24 months (EFS24) is a well validated endpoint in DLBCL (Maurer et al, 2014) and is clinically relevant in older patients. We hypothesized that baseline clinical factors and QOL would be associated with EFS24 this patient group. Methods Newly diagnosed lymphoma patients were prospectively enrolled within 9 months of diagnosis into the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER). Patients ≥70 years of age with DLBCL were utilized in this study. All pathology was reviewed by a lymphoma hematopathologist. Clinical variables were abstracted from the medical record. QOL was assessed at enrollment using a single item Linear Analogue Self-Assessment (LASA) and the 27-item Functional Assessment of Cancer Treatment-General questionnaire (FACT-G), which includes physical, social, emotional, and functional well-being domains. QOL scores were converted to a 0-100 scale to facilitate modeling. QOL was analyzed in patients who completed 80% of the FACT-G questions. Characteristics of the study population were compared using the Wilcoxon rank sum test. Odds ratios (ORs) and 95% confidence intervals (CI) were used to estimate the associations of clinical and continuous QOL variables with failure to achieve EFS24 using logistic regression models, with a stepwise approach to identify parsimonious multivariate models. Results A total of 389 patients ≥70 years were identified with DLBCL in the MER from 2002-2015; patient characteristics are described in the Table. In the entire study population, univariate predictors of EFS24 failure included age (OR per 10 years=1.85, 95% CI: 1.26-2.71), ECOG PS ≥2 (OR=4.78, 95% CI: 2.92-7.83), elevated LDH (OR=3.59, 95% CI: 2.27-5.65), stage III-IV (OR=1.94, 1.25-3.02), bulky disease (OR=2.86, 95% CI: 1.43-5.72), international prognostic index (OR=8.71 for IPI 5 vs IPI 0, 95% CI: 3.04-24.9), and receipt of an anthracycline (OR=0.25, 95% CI: 0.12-0.51), while none of the other variables in the Table, including the QOL variables, were statistically significant. In a stepwise multivariate analysis, only ECOG PS ≥2 (OR= 3.56, 95% CI: 2.09-6.06) and elevated LDH (OR=2.86, 95% CI: 1.78-4.60) remained significant predictors of EFS24 failure. QOL data were available on 220 patients, with 120 completing QOL questionnaires prior to receipt of chemotherapy. Compared to participants who completed their FACT-G before the initiation of chemotherapy, the median FACT-G physical (85.7 v. 71.4, p=0.005) and functional (71.4 vs 57.1, p=0.008) scores were lower in participants completing FACT-G after initiation of therapy, were higher on FACT-G emotional (79.2 vs 83.3, p=0.03), and showed no differences on FACT-G social (89.3 vs 91.7, p=0.60) or FACT-G total score (78.2 vs 74.1, p=0.17). Given these differences, we restricted the QOL analysis to those with pre-treatment data. In univariate analysis, the LASA score (OR= 0.98, 95% CI: 0.84-1.14), the FACT-G total (OR=0.99, 95% CI: 0.96-1.01), physical (OR=0.98, 95% CI: 0.97-1.00), social (OR=1.00, 95% CI: 0.98-1.03), emotional (OR= 1.00, 95% CI: 0.98-1.02), and functional (OR=0.99, 95% CI: 0.98-1.01) scores were not associated with EFS24 failure. In a stepwise multivariate analysis of clinical variables in patients with pretreatment QOL scores, only ECOG PS ≥2 (OR=3.56, 95% CI: 1.30-9.72) and female sex (OR=0.37, 95% CI: 0.16-0.85) were associated with failure to achieve EFS24. Conclusions In patients aged 70 years and older, ECOG PS and LDH were the strongest independent predictors of failure to achieve EFS24. As expected, physical and functional scores were lower in patients who completed their QOL after initiation of treatment. Restricting the analysis to patients with pre-treatment data, QOL was not associated with failure to achieve EFS24. Additional studies are needed to identify the most robust clinical predictors of EFS24, while QOL does not appear to be an important predictor of EFS24. Disclosures Reagan: Seattle Genetics: Research Funding. Maurer:Morphosys: Research Funding; Celgene: Research Funding; Nanostring: Research Funding. Cerhan:Celgene: Research Funding; Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board.

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A Retrospective Evaluation Of Insurance Status As It Relates To Outcomes In Diffuse Large B-Cell Lymphoma

Blood ◽

10.1182/blood.v122.21.1702.1702 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1702-1702

Author(s):

Bryan J Little ◽

Julio C Chavez ◽

Celeste M. Bello ◽

Paul Chervenick ◽

Lubomir Sokol ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Survival Time ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Insurance Status ◽

Event Free Survival ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell

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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Long Term Results of the GELA Study, R-CHOP vs. CHOP in Elderly Patients with Diffuse Large B-Cell Lymphoma.

Blood ◽

10.1182/blood.v104.11.1383.1383 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1383-1383 ◽

Cited By ~ 1

Author(s):

Bertrand Coiffier ◽

Pierre Feugier ◽

Catherine Sebban ◽

Reda Bouabdallah ◽

Vincent Delwail ◽

...

Keyword(s):

Overall Survival ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Long Term Results ◽

Event Free Survival ◽

Free Survival ◽

Large B Cell Lymphoma ◽

New Treatment

Abstract In 1998, the GELA (Groupe d’Etude des Lymphomes de l’Adulte) ran a randomized study to evaluate the benefit of the addition of rituximab to CHOP chemotherapy in elderly patients (60 to 80 years old) with diffuse large B-cell lymphoma. Early results were presented at ASH 2000 and published in NEJM (2002;346:235) with a median follow-up of 1 and 2 years, respectively. An update of these results is presented with a median follow-up of 5 years. 399 patients were included, 197 in the CHOP group and 202 in the R-CHOP group, 60% had a high risk disease according to the IPI score. Characteristics of the patients did not differ between both groups. Rituximab was given at 375 mg/m² the same day of CHOP for 8 cycles. Primary endpoint was event-free survival with events defined as progressive disease (PD) during or after treatment, relapse, institution of a new treatment, and death whatever the cause. Secondary endpoints were overall survival (OS) and progression-free survival (PFS) with progression defined as PD, relapse, or death from lymphoma or lymphoma treatment. Response rates for R-CHOP and CHOP were: CR/CRu 75% and 63%, PD 9% and 22%, and death during treatment 6% and 6%, respectively (P=.005), as previously published. With a median follow-up of 5 years, 106 events (52.5% of the patients) were observed in R-CHOP arm and 142 (72%) in CHOP arm: 19% and 31% PD or death during treatment, 5.5% and 4.5% institution of a new treatment, 20% and 34% relapses, 8% and 2.5% death in CR for R-CHOP and CHOP, respectively. Survival outcomes are presented in the table. Table 1. 5-year survivals R-CHOP CHOP P value Median event-free survival 3.8 y 1.1 y =0.00002 5-year event-free survival 47% 29% Median progression-free survival Not reached 1 y <0.00001 5-year progression-free survival 54% 30% Median overall survival Not reached 3.1 y =0.0073 5-year overall survival 58% 45% Progression-free survival is shown in the figure; PFS does not included 19 patients who died in CR from causes not related to lymphoma or its treatment, 5 in CHOP arm and 14 in R-CHOP arm. It better reflects the long term effect of treatment on the disease. No severe late toxicity was observed in R-CHOP treated patients and deaths not related to lymphoma did not show any pattern. In conclusion, long term results continue to show a major benefit for the addition of rituximab to CHOP in the treatment of patients with DLBCL. This improvement increases with time.

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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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Vitamin D Deficiency Is Associated with Inferior Event-Free and Overall Survival in Diffuse Large B-Cell Lymphoma.

Blood ◽

10.1182/blood.v114.22.1952.1952 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1952-1952

Author(s):

Matthew T Drake ◽

Matthew J Maurer ◽

Brian K Link ◽

Ivana N Micallef ◽

Thomas M Habermann ◽

...

Keyword(s):

Clinical Trial ◽

Vitamin D ◽

Overall Survival ◽

Vitamin D Deficiency ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Event Free Survival ◽

Free Survival ◽

Large B Cell Lymphoma

Abstract Abstract 1952 Poster Board I-975 Background: Vitamin D is a naturally occurring steroid hormone. In addition to its well-established role in maintaining serum calcium homeostasis, vitamin D has effects on cellular differentiation, proliferation, apoptosis, and angiogenesis. Vitamin D3 is naturally produced in skin in response ultraviolet-B (UVB) radiation from the sun. Several recent studies, however, have shown that a high proportion of community-dwelling subjects in both tropical and temperate climates are deficient in vitamin D, and that subjects in northern latitudes often require dietary supplementation to maintain vitamin D sufficiency. Further, several reports now suggest that vitamin D sufficiency is protective against the development of several cancers, including non-Hodgkin lymphoma (NHL). However, it is not known whether vitamin D impacts prognosis in diffuse large B-cell lymphoma (DLBCL), the most common NHL subtype. Methods: We evaluated serum vitamin D concentrations in two cohorts of DLBCL patients. The first cohort consisted of 374 patients newly diagnosed from September 2002-February 2008 who were prospectively enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource, an observational study in which neither therapeutic nor diagnostic management is prescribed. All serum was obtained within 120 days of diagnosis, and was prior to treatment in 221 (59%). In the second study, 62 patients newly diagnosed from February 2006-August 2007 were enrolled on NCCTG clinical trial N0489, and all serum was obtained before the first course of therapy. Central pathology review was performed on all patients to confirm the diagnosis of DLBCL. Serum 25-hydroxyvitamin (25-OH-VitD) levels were measured by the gold standard method for vitamin D determination: liquid chromatography tandem mass spectroscopy (LC-MS/MS). Vitamin D deficiency was defined as total serum 25-OH-VitD < 25 ng/mL (62.5 nmol/L). SPORE patients were followed per a standard protocol for event-free (progression, retreatment, or death due to any cause) and overall survival (EFS and OS, respectively); N0489 patients were followed in a similar way per the clinical trial protocol. We used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CI). Results: SPORE patients were primarily treated with immunochemotherapy (83%); all N0489 patients were treated with epratuzumab + R-CHOP21. The median age at diagnosis was 62 years (range, 19-93) for SPORE patients and 61 years (range, 21-82) for N0489 patients. Median follow-up for SPORE patients was 36 months (range, 1-77) with 95 deaths and 131 events; median follow-up for N0489 patients was 24 months (range, 7-39) with 13 deaths and 18 events. Vitamin D deficiency was identified in 188 SPORE patients (50%) and 15 N0489 patients (24%). There were no differences in the prevalence of vitamin D deficiency by age, IPI, or whether serum was obtained prior to starting treatment (all p > 0.28). Vitamin D deficiency was associated with inferior overall (HR=2.33, 95% CI 1.53-3.57, logrank p = 0.0001) and event-free survival (HR=1.71, 95% CI 1.20-2.44, logrank p = 0.003) in the SPORE cohort. These associations remained significant after adjusting for IPI and treatment: OS HR=1.97, 95% CI 1.27-3.07; EFS HR=1.47, 95% CI 1.02-2.21. These results were similar for the subset of SPORE patients who were treated with R-CHOP. The HRs for vitamin D deficiency and event-free survival were consistent in the N0489 patients (HR=1.63, 95% CI 0.61-4.35, IPI adjusted HR=1.43, 95% CI 0.53-3.85), although these results lacked precision due to a smaller sample size. We were unable to evaluate OS in N0489 due to the small number of deaths. Conclusions: Approximately 50% of all DLBCL patients in this northern US latitude population are vitamin D deficient at the time of diagnosis and treatment. Vitamin D deficient patients have an inferior event-free and overall survival compared to patients with vitamin D levels within the normal range. Vitamin D supplementation during treatment of DLBCL patients with vitamin D deficiency should be evaluated in a clinical trial setting. Disclosures: No relevant conflicts of interest to declare.

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The Neutrophil/Lymphocyte Ratio (N/L) Is a Prognostic Marker in Patients with Diffuse Large B Cell Lymphoma: A Prospective Study from the Lazio Lymphoma Registry

Blood ◽

10.1182/blood.v128.22.3050.3050 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3050-3050

Author(s):

Ombretta Annibali ◽

Stefan Hohaus ◽

Valeria Tomarchio ◽

Paola Anticoli Borza ◽

Maria Cantonetti ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Prognostic Marker ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Event Free Survival ◽

Free Survival ◽

Neutrophil Lymphocyte Ratio ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract The neutrophil/lymphocyte ratio (N/L) at diagnosis has been shown to be a prognostic factor for survival in solid tumors. An increase in the neutrophil count is a marker of inflammation which is an essential part of the neoplastic process. Conversely, a decrease of the peripheral lymphocyte count might reflect an impairment of the host defense mechanism associated with advanced and aggressive cancers. Since There are only few reports on the N/L ratio in non-Hodgkin lymphomas. We studied the prognostic role of the N/L ratio at diagnosis in 286 patients with diffuse-large-B-cell lymphoma (DLBCL) enrolled in a multicenter prospective registry of the Lazio region in Italy The median age at diagnosis was 69 years (27-91) and the female/male ratio was:141/145.First, we analyzed for associations between N/L ratio and patient characteristics. The optimal cut-off value for the N/L was obtained using the Receiver Operating Curve (ROC) and according to the published data in solid tumor. N/L ≥ 4 was significantly associated with presence of B-symptoms (p=0.01) and elevated LDH levels (p=0.007) at diagnosis. Most patients were treated with R-CHOP (rituximab, cyclophosphamide, Adriamycin, vincristine, and prednisone) or R-CHOP-like (90%). Complete Remission (CR) + Partial Remission (PR) were obtained in 210/286 (73%). The median follow up period was 15 months (range: 1-33 months): 27 patients died for lymphoma relapse/progression and 16 for other causes. Patients with N/L ≥ 4 experienced a higher rate of relapse, while N/L< 4 was associated to a significantly better Overall (OS, P < 0.05) and Event Free Survival (EFS, P< 0.01). (Figure 1, panel a and b).Furthermore, considering only patients with IPI score ≤ 3, those with N/L <4, (Figure 1, panel c), had a better OS compared to those with N/L≥ 4 (P < 0.01). Conclusion: The N/L ratio may be a useful and unexpensive prognostic marker in patients with DLBCL. The inferior outcome observed in patients with N/L ≥ 4 might reflect an immune and inflammatory imbalance induced by a more aggressive tumor, releasing directly or indirectly inflammatory cytokines and/or inducing immune suppression or exhaustion. A link with inflammation is suggested by the correlation of N/L ratio ≥ 4 with high LDH levels and the presence of B symptoms. Figure 1. Panel A. Overall Survival (OS) and Panel B. Event Free Survival (EFS) by N/L ratio. Panel C. Overall Survival (OS) by N/L in patients with IPI score ≤ 3. Table 1.Baseline patients characteristics (N = 268) and compared by N/L < 4 or ≥ 4 by using Chi-Square Test for categorical variables. Abbreviations not included in the text: IPI = International Prognostic Index; LDH = lactate dehydrogenase, PD: Progression Disease, NA: Not Applicable. Disclosures Cimino: Celgene: Honoraria; Bristol-Mayer: Honoraria.

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The Expression of CD44v6 Predicts Poor Outcome in Patients with Diffuse Large B Cell Lymphoma Treated with R-CHOP

Blood ◽

10.1182/blood.v124.21.5386.5386 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5386-5386

Author(s):

Yongqiang Wei ◽

Muchen Xie ◽

Fen Huang ◽

Xiaolei Wei ◽

Hui Jing ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Prognostic Value ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Event Free Survival ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

Cd44v6 Expression

Abstract Background: CD44 variants have been implicated in metastasis and as an unfavorable prognosis factor in many types of cancers. Our previous study had showed that CD44v6 expression implied a poor clinical outcome in diffuse large B cell lymphoma (DLBCL) patients treated with CHOP. However, it is remains unknown the prognostic value in DLBCL patients treated with R-CHOP due to our sample sizes. Therefore, to examine the prognostic value of CD44v6 expression in DLBCL patients, we performed this retrospective study. Methods: All 141 patients diagnosed as de novo DLBCL according to WHO classification were further confirmed. All patients treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone). The expression of CD44v6 was analyzed by immunohistochemistry (IHC). IHC was performed by an automated immunostainer complying with the instructions of the protocols. Results: Among all the 141 patients, the expression of CD44v6 was observed in 41 cases (29.1%). CD44v6 is expressed predominantly in non-germinal center type DLBCL. There was no significant difference in gender, age, B symptoms, performance status, LDH, stage and IPI score between patients with and without CD44v6 expression. Patients with CD44v6 expression showed significant inferior overall survival, but not event-free survival compared with CD44v6-negative patients. (p=0.022 and p=0.142, respectively).Multivariate analysis showed that the expression of CD44v6, independent of the international prognostic index and cell of origin, implied a poor overall survival (HR=2.223; 95% CI= 1.007-4.906, p=0.048), but not event-free survival (HR=1.457; 95% CI=0.773-2.745, p=0.245). Conclusions: These data suggest that the expression of CD44v6 implied poor outcome in DLBCL patients treated with R-CHOP. Disclosures No relevant conflicts of interest to declare.

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Real-world practice patterns and outcomes in Veterans with relapsed/refractory diffuse large B-cell lymphoma

Future Oncology ◽

10.2217/fon-2020-0522 ◽

2020 ◽

Author(s):

Hsu-Chih Chien ◽

Deborah Morreall ◽

Vikas Patil ◽

Kelli M Rasmussen ◽

Chunyang Li ◽

...

Keyword(s):

Overall Survival ◽

B Cell ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Line Treatment ◽

Electronic Health Record Data ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell

Aim: To describe practices and outcomes in veterans with relapsed/refractory diffuse large B-cell lymphoma. Patients & methods: Using Veteran Affairs Cancer Registry System and electronic health record data, we identified relapsed/refractory diffuse large B-cell lymphoma patients completing second-line treatment (2L) in 2000–2016. Treatments were classified as aggressive/nonaggressive. Analyses included descriptive statistics and the Kaplan–Meier estimation of progression-free survival and overall survival. Results: Two hundred and seventy patients received 2L. During median 9.7-month follow-up starting from 2L, 470 regimens were observed, averaging 2.7 regimens/patient: 219 aggressive, 251 nonaggressive. One hundred and twenty-one patients proceeded to third-line, 50 to fourth-line and 18 to fifth-line treatment. Median progression-free survival in 2L was 5.2 months. Median overall survival was 9.5 months. Forty-four patients (16.3%) proceeded to bone marrow transplant. Conclusion: More effective, less toxic treatments are needed and should be initiated earlier in treatment trajectory.

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