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

Blood ◽  
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.

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 ◽  
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.

R-CHOP compared with CHOP in patients with diffuse large B-cell lymphoma (DLCL): Russian experience

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18536-18536 ◽  
Author(s):  
I. Poddubnaya ◽  
E. Osmanov ◽  
L. Babicheva ◽  
G. Tumyan ◽  
E. Sorokin ◽  
...  
Keyword(s):  
Median Overall Survival ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Event Free Survival ◽  
Relapse Free Survival ◽  
Bulky Disease ◽  
Free Survival ◽  
Large B Cell Lymphoma

18536 Background: R-CHOP is regarded as the best available treatment for untreated patients with aggressive and indolent B- NHL. Methods: 184 previously untreated patients with DLCL were included in retrospective study: 92 patients were treated by CHOP, 92 patients were treated by CHOP plus rituximab ( R-CHOP ). Age of patients ranged 16–87 years (median 50 years). The median follow- up was 18 months. Compared groups were balanced in all parameters. The advanced stage of disease (III-IV) at diagnosis had 66% patients treated with CHOP and 67,5 % patients treated with R-CHOP. =2 extranodal zones were initially revealed at 35% in CHOP group vs 47% in R- CHOP group. PS of 25 % patients in R-CHOP group and 30% patients in CHOP group was regarded as appropriate 3–4 degrees on ECOG. Increased LDH level was marked at 60% in CHOP-group vs 54% in R-CHOP. 29% patients in R-CHOP group and 21% patients in CHOP group had B-symptoms at diagnosis; bulky disease took place in 53% cases in R-CHOP group and 62% cases in CHOP. High IPI score had 47 % patients in CHOP-group vs 48 % in R-CHOP. Results: Complete response was achieved in 74% of the patients treated with R- CHOP, as compared to 56% of those treated with CHOP alone (p<0,05). Disease progression during treatment was reported in 25% of patients in CHOP group and 18,5% in R-CHOP group. Median overall survival in patients treated with R-CHOP was NS, in patients treated with CHOP alone was 16 months. With a median follow-up of 18 months, 29 (31,5%) events (progression - 18,5%, relapse - 10%, death - 3% ) were observed in the R-CHOP group and 48 (52%) events ( progression - 25%, relapse - 20%, death - 7%) in the CHOP group (p<0,05). Median event-free survival and relapse-free survival in the CHOP group was 12 months, in R-CHOP group NS. Toxicity was equivalent in both groups. Conclusions: We have established better direct efficiency and outcome of R-CHOP in any age of pts. No significant financial relationships to disclose.

Impact of Organ Function–Based Clinical Trial Eligibility Criteria in Patients With Diffuse Large B-Cell Lymphoma: Who Gets Left Behind?

2021 ◽  
pp. JCO.20.01935
Author(s):  
Arushi Khurana ◽  
Raphael Mwangi ◽  
Grzegorz S. Nowakowski ◽  
Thomas M. Habermann ◽  
Stephen M. Ansell ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Event Free Survival ◽  
Organ Function ◽  
Eligibility Criteria ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Hazard Ratios ◽  
Large B Cell

PURPOSE Exclusion of patients needing urgent treatment or requiring novel biomarkers before enrollment has impacted the ability to enroll real-world patients in frontline trials of diffuse large B-cell lymphoma (DLBCL). The impact of baseline organ function–based eligibility criteria on this effect and clinical trial exclusion is less well-understood. METHODS Consecutive patients with newly diagnosed lymphoma were enrolled from 2002 to 2015 into the Molecular Epidemiology Resource (MER) of the University of Iowa and Mayo Clinic Lymphoma Specialized Program of Research Excellence. The current analysis includes 1,265 patients with DLBCL receiving standard immunochemotherapy. Organ function parameters were identified from criteria for hemoglobin, absolute neutrophil count, platelet count, creatinine clearance, and bilirubin, as reported in frontline DLBCL trials. Abstracted laboratory values from MER were used to determine the percent (%) of patients excluded. Outcomes and cause-of-death analyses comparing ineligible and eligible groups in MER were conducted. An interactive online tool was developed to estimate exclusions based on organ function for future trial design. RESULTS Between 9% and 24% of MER patients with DLBCL receiving standard immunochemotherapy were excluded on the basis of baseline organ function alone. Ineligible patients based on organ function had significantly inferior event-free survival (hazard ratios, 1.67-2.16), overall survival (hazard ratios, 1.87-2.56), and event-free survival at 24 months (odds ratio, 1.71-2.16). Ineligible patients were more likely to die from lymphoma progression than increased therapy-related complications. CONCLUSION Current national and international trials exclude up to 24% of patients from participation on the basis of organ function alone. A significant difference in the outcomes, notably lymphoma-related death, suggests issues with generalization and potential exclusion of high-risk patients. These data will help future clinical trial development and meet US Food and Drug Administration and ASCO recommendations to increase trial accrual.

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.

Introduction of Combined CHOP Plus Rituximab Therapy Dramatically Improved Outcome of Diffuse Large B-Cell Lymphoma in British Columbia

2005 ◽  
Vol 23 (22) ◽  
pp. 5027-5033 ◽  
Author(s):  
Laurie H. Sehn ◽  
Jane Donaldson ◽  
Mukesh Chhanabhai ◽  
Catherine Fitzgerald ◽  
Karamjit Gill ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Ratio ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Survival Risk ◽  
Large B Cell

Purpose For more than two decades, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) has been the standard therapy for diffuse large B-cell lymphoma (DLBCL). The addition of rituximab to CHOP has been shown to improve outcome in elderly patients with DLBCL. We conducted a population-based analysis to assess the impact of this combination therapy on adult patients with DLBCL in the province of British Columbia (BC). Methods We compared outcomes during a 3-year period; 18 months before (prerituximab) and 18 months after (postrituximab) institution of a policy recommending the combination of CHOP and rituximab for all patients with newly diagnosed advanced-stage (stage III or IV or stage I or II with “B” symptoms or bulky [> 10 cm] disease) DLBCL. Results A total of 292 patients were evaluated; 140 in the prerituximab group (median follow-up, 42 months) and 152 in the postrituximab group (median follow-up, 24 months). Both progression-free survival (risk ratio, 0.56; 95% CI, 0.39 to 0.81; P = .002) and overall survival (risk ratio, 0.40; 95% CI, 0.27 to 0.61, P < .0001) were significantly improved in the postrituximab group. After controlling for age and International Prognostic Index score, era of treatment remained a strong independent predictor of progression-free survival (risk ratio, 0.59; 95% CI, 0.41 to 0.85; P = .005) and overall survival (risk ratio, 0.43; 95% CI, 0.29 to 0.66; P < .001). The benefit of treatment in the postrituximab era was present regardless of age. Conclusion The addition of rituximab to CHOP chemotherapy has resulted in a dramatic improvement in outcome for DLBCL patients of all ages in the province of BC.

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

Blood ◽  
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.

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

2017 ◽  
Vol 35 (5) ◽  
pp. 544-551 ◽  
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.

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

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1383-1383 ◽  
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 &lt;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.

Elevated Pre-Treatment Serum Immunoglobulin Free Light Chains (FLC) Are Associated with Poor Event-Free and Overall Survival in Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 136-136 ◽  
Author(s):  
Matthew J Maurer ◽  
Ivana N Micallef ◽  
Jerry A Katzmann ◽  
Daniel Nikcevich ◽  
Thomas E Witzig
Keyword(s):  
Clinical Trial ◽  
Overall Survival ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Light Chains ◽  
Large B Cell Lymphoma ◽  
Pre Treatment ◽  
Large B Cell

Abstract Abstract 136 Background: The serum free light chain (FLC) assay quantitates free kappa and free lambda immunoglobulin light chains. This assay has prognostic value in MGUS, multiple myeloma (MM), solitary plasmacytoma, and AL amyloidoisis, and has been incorporated in response criteria for both MM and AL amyloidosis. A percentage of non-Hodgkin's lymphoma (NHL) patients also present with abnormal FLC concentrations and recent data suggest that AIDS patients with elevated serum FLC are at higher risk of developing NHL. Here we assess the impact of FLC in a cohort of patients with diffuse large B-cell lymphoma (DLBCL) enrolled on a cooperative group clinical trial. Methods: Newly diagnosed DLBCL patients were treated with epratuzumab + R-CHOP (ER-CHOP) on NCCTG clinical trial N0489. Serum FLC was quantitated prior to treatment and after cycles 2 and 6 using the Freelite FLC assay (The Binding Site, Ltd., Birmingham, UK). Patients were followed per clinical trial protocol for event-free (progression, retreatment, or death due to any cause) and overall survival (EFS and OS, respectively). Results: 107 patients were enrolled on the trial. 80 patients had a pre-treatment serum draw and a central pathology confirmed diagnosis of DLBCL, of which 47 had a post-cycle 2 sample (C2) and a 54 had a post-cycle 6 sample (C6). At a medium follow-up of 25 months (range 7-39), 22 patients (28%) had an event and 17 patients died (21%). Prior to treatment 23 patients (29%) had abnormal kappa concentrations (all elevated), 16 (20%) had abnormal lambda concentrations (11 elevated, 5 decreased), and 9 (11%) had an abnormal kappa/lambda ratio. FLC concentrations were significantly reduced in patients during treatment, with a median reduction in kappa (C2: 46%, C6: 64%) and lambda (C2: 44%, C6: 49%), all p<0.0001. Elevated FLC prior to treatment was highly associated with both OS (logrank p=0.009) and EFS (logrank p=0.006); these associations remained significant after adjusting for IPI (both p = 0.01). Conclusions: A significant percentage of DLBCL patients present with abnormal FLC concentrations. Kappa and lambda are significantly reduced for most patients during treatment. Elevated pre-treatment FLC concentrations are associated with inferior EFS and OS in DLBCL and this association is independent of the IPI. A follow-up study of FLC and prognosis is currently underway in a cohort of 1500 NHL patients from the Mayo Clinic and University of Iowa SPORE. Disclosures: No relevant conflicts of interest to declare.

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 ◽  
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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