Dose-Dense Rituximab Improves Outcome of Elderly Patients with Poor-Prognosis Diffuse Large B-Cell Lymphoma (DLBCL): Results of the DENSE-R-CHOP-14 Trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 789-789 ◽  
Author(s):  
Michael Pfreundschuh ◽  
Samira Zeynalova ◽  
Viola Poeschel ◽  
Mathias Haenel ◽  
Norbert Schmitz ◽  
...  
Keyword(s):  
Complete Remission ◽  
Elderly Patients ◽  
Poor Prognosis ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Serum Levels ◽  
Event Free Survival ◽  
Free Survival ◽  
Dose Dense ◽  
Patients With Poor Prognosis

Abstract Background: While 6 to 8 cycles of CHOP in combination with rituximab are widely accepted as standard regimen of care for aggressive lymphomas, the optimal dose and number of rituximab application have not been determined to date. In a previous pharmacokinetic study we had shown that the concomitant application of CHOP and rituximab does not achieve a plateau of rituximab trough levels until cycle 5 (Reiser, Blood 108, 778a, 2006). In order to achieve high rituximab levels early, we increased the number of rituximab applications. Methods: 100 elderly patients with aggressive CD20+ B-cell lymphoma received 6 cycles of biweekly CHOP-14 combined with 12x rituximab (375 mg/m2) on days 0, 1, 4, 8, 15, 22, 29, 43, 57, 71, 85, and 99. Radiotherapy was planned to sites of initial bulk and/or extranodal involvement. The primary endpoint was event-free survival (EFS). 306 patients treated within the RICOVER-60 trial (Pfreundschuh et al., Blood 64a, 2006) with 6xCHOP-14 and 8 applications of rituximab served as control. Results: 97/100 patients are evaluable for response. Dose-dense rituximab resulted in plateau trough serum levels of rituximab as early as day 1 of the first chemotherapy cycle and higher rituximab levels were maintained throughout the treatment compared to 8 bi-weekly applications. Because 3 therapy-associated deaths were observed among the first 20 patients treated, prophylaxis with levofloxacin, acyclovir and cotrimoxazol became mandatory for the following patients. Despite a less favorable study population DENSE-R-CHOP-14 resulted in a somewhat higher complete remission (83% vs. 78%) and lower progression under therapy rate (5% vs. 7%) rate, but event free and overall survival were not different compared to 8 biweekly applications of rituximab. However, a subgroup analysis of patients according to IPI risk group showed that DENSER-R-CHOP-14 resulted in a higher complete response rate of patients with poor-prognosis (IPI:3–5) disease (81% vs. 68%). This advantage translated into a better 1-year event-free survival rate (74% vs. 65%) of these patients. Conclusion: In combination with 6 cycles of CHOP-14 densification of rituximab achieves higher rituximab serum levels and results in higher complete remission and event-free survival rates in elderly patients with poor-prognosis DLBCL. These observations from a phase-II trial must be confirmed in a randomized study.

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.

scholarly journals Age-dependent increase of treatment-related mortality in older patients with aggressive B cell lymphoma: analysis of outcome, treatment feasibility, and toxicity in 1171 elderly patients with aggressive B cell lymphoma—data from phase II and III trials of the DSHNHL (German High-Grade Non-Hodgkin’s Lymphoma Study Group)

2020 ◽  
Author(s):  
Florian Zettl ◽  
Marita Ziepert ◽  
Bettina Altmann ◽  
Samira Zeynalova ◽  
Gerhard Held ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Patient Population ◽  
Cell Lymphoma ◽  
Age Groups ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Age Dependent ◽  
Aggressive B Cell Lymphoma

AbstractIn elderly patients (pts) with aggressive B cell lymphoma (aNHL), curative treatment often cannot be administered because of comorbidities and tolerability. We analyzed the influence of age in pts > 60 years receiving the R-CHOP-14 regimen within different prospective DSHNHL trials. Of the RICOVER-60 trial and CHOP-R-ESC trials, 1171 aNHL pts were included in this retrospective analysis of age-dependent event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). All patients received prophylactic G-CSF, and anti-infective prophylaxis with amphotericin B mouth wash and oral fluorchinolone was optional. In the CHOP-R-ESC trials, prophylaxis was augmented to include mandatory continuous orally administered aciclovir and a pneumocystis prophylaxis with cotrimoxazole as well as oral fluorchinolones during neutropenia. The patient population was separated into 4 age groups (61–65 years, 66–70 years, 71–75 years, and 76–80 years). The results from the RICOVER-60 trial were subsequently confirmed in the following CHOP-R-ESC trials by a multivariate analysis adjusted for IPI factors and gender. Significant differences (p < 0.001) in EFS, PFS, and OS were seen between age groups (RICOVER-60). Hematotoxicity, infections, and TRM increased with age. TRM was significantly elevated in the age group 76–80 years. Therefore, this analysis shows that an age above 75 years defines an especially vulnerable patient population when being treated with chemoimmunotherapy for aNHL. Prophylactic anti-infective drugs are essential and clinically effective in reducing morbidity when treating elderly aNHL pts.

scholarly journals International Assessment of Event-Free Survival at 24 Months and Subsequent Survival in Peripheral T-Cell Lymphoma

2017 ◽  
Vol 35 (36) ◽  
pp. 4019-4026 ◽  
Author(s):  
Matthew J. Maurer ◽  
Fredrik Ellin ◽  
Line Srour ◽  
Mats Jerkeman ◽  
N. Nora Bennani ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
The United States ◽  
Primary Treatment ◽  
Patient Counseling ◽  
Event Free Survival ◽  
Curative Intent ◽  
Free Survival ◽  
Younger Patients

Purpose Peripheral T-cell lymphomas (PTCLs) have aggressive clinical behavior. We have previously shown that event-free survival (EFS) at 24 months (EFS24) is a clinically useful end point in diffuse large B-cell lymphoma. Here, we assess EFS24 and subsequent overall survival (OS) in large, multinational PTCL cohorts. Patients and Methods Patients with systemic PTCL newly diagnosed from 2000 to 2012 and treated with curative intent were included from the United States and Sweden (initial cohorts) and from Canada (replication cohort). EFS was defined as time from date of diagnosis to progression after primary treatment, retreatment, or death. Subsequent OS was measured after achieving EFS24 or from the time of progression if it occurred within 24 months. OS rates were compared with the age-, sex-, and country-matched general population. Results Seven hundred seventy-five patients were included in the study (the median age at diagnosis was 64 years; 63% were men). Results were similar in the initial and replication cohorts, and a combined analysis was undertaken. Sixty-four percent of patients progressed within the first 24 months and had a median OS of only 4.9 months (5-year OS, 11%). In contrast, median OS after achieving EFS24 was not reached (5-year OS, 78%), although relapses within 5 years of achieving EFS24 occurred in 23% of patients. Superior outcomes after achieving EFS24 were observed in younger patients (≤ 60 years of age: 5-year OS, 91%). Conclusion EFS24 stratifies subsequent outcome in PTCL. Patients with PTCL with primary refractory disease or early relapse have extremely poor survival. However, more than one third of patients with PTCL remain in remission 2 years after diagnosis with encouraging subsequent OS, especially in younger patients. These marked differences in outcome suggest that EFS24 has utility for patient counseling, study design, and risk stratification in PTCL.

Multimodal Dose Dense Therapy for Mantle Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1163-1163
Author(s):  
Sam O. Wanko ◽  
Jon P. Gocherman ◽  
Joseph O. Moore ◽  
Carlos Decastro ◽  
Robert Prosnitz ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Induction Therapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Mantle Cell ◽  
Dose Dense

Abstract BACKGROUND: Mantle cell lymphoma (MCL) typically has a poor outcome with overall survival of only 3–4 years. Higher treatment response and event-free survival has been demonstrated with aggressive high dose chemotherapy followed by autologous hematopoietic stem cell support, though long term cure rates remain unclear(Dreger P. Hematol J. 2000;vol.2). Modest response rates have also been reported with the monoclonal antibody (MoAb) rituximab and ALEMTUZUMAB (Foran, JM. JCO 2000; vol. 2. Faderl S. Blood 2003; vol. 9). We therefore combined dose-dense therapy with MoAbs to explore response rate and event free survival (EFS) in mantle cell lymphoma. The strength of this trial design is ability to follow all patients from induction chemotherapy through high dose therapy and transplant in order to gauge clinical outcome on all enrolled patients, not just the subpopulation who is able to proceed to high dose therapy. PATIENTS AND METHODS: Induction therapy consisted of 1 cycle of high dose cytarabine (3gm/m2 IV over 1 hour Q12H for 8 doses), mitoxantrone (10mg/m2 daily for 3 days), and ALEMTUZUMAB 30mg IV 3 times a week for 6 weeks with growth factor support. All responding patients were mobilized with cyclophosphamide 4gm/m2 and G-CSF 10 mcg/kg/day and/or bone marrow harvest. The transplant preparative regimen was carmustine 15mg/kg over 2 hours day -6, etoposide 60mg/kg over 4 hours day -4, and cyclophosphamide 100mg/kg over 2 hours day -2 followed by autologous reinfusion on day zero. Consolidation was given with rituximab 375mg/m2 weekly for 4 doses at 6 weeks and 6 months post transplant. RESULT: 9 patients with advanced disease (7 stage IV, 1 stage III, 1 stage IIA) and median age of 60 (48 – 65 years) have been accrued and treated since February 2003. Four were newly diagnosed and 5 had relapsed/refractory disease. Seventy eight percent (7/9) had complete response and 22% (2/9) had partial response (PR) following induction therapy. One patient had severe infection after induction and was unable to proceed to transplant. Another had constitutional decline preventing further therapy and each died within 4 months of withdrawal from the protocol. Both had relapse/refractory disease at accrual. The remaining 7 patients proceeded to the transplant phase. With a median follow-up of 7 months (range 3–16 months), all 7 patients remain in CR for 1 –16 months. Significant induction therapy toxicity included neutropenia in all 9 patients with average duration of 10.7 days, non-disseminated CMV reactivation in 44% of patients, one overwhelming fungal infection, and one patient with delay in engraftment. Figure Figure CONCLUSION: Our preliminary data show a high induction and transplant phase completion rate, manageable toxicity, and excellent overall response rate in this group of elderly patients with advanced disease. Larger numbers of patients and longer follow-up is needed to confirm these promising results.

Serum Interleukin-18 Level Determines Clinical Outcome in Patients with Diffuse Large B-Cell Lymphoma in Rituximab Era.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1926-1926
Author(s):  
Naoe Goto ◽  
Hisashi Tsurumi ◽  
Senji Kasahara ◽  
Takeshi Hara ◽  
Nobuhiro Kanemura ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Serum Levels ◽  
High Serum ◽  
Interleukin 18 ◽  
Free Survival ◽  
Large B Cell Lymphoma ◽  
Good Risk

Abstract Abstract 1926 Poster Board I-949 Purpose: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous entity, with patients exhibiting a wide range of outcomes. The introduction of rituximab to CHOP (R-CHOP) has significantly altered improvement in survival. This raises concern regarding the utility of previously identified prognostic factors. Before rituximub era, some investigators have suggested that serum levels of some cytokines and their soluble receptors might reflect tumor growth and host tumor responses. Interleukin-18 (IL-18), originally designated as an interferon (IFN)-gamma inducing factor, is a cytokein which stimulates cytotoxic NK cell activity and T cells to produce IFN-gamma, IL-2, and GM-CSF. Increased IL-18 serum levels have been found in patients with some hematopoietic neoplasms. IL-18 is also immunostimulatory cytokine with antitumor activity in preclinical models, and a phase I study of recombinant human IL-18 was done to patients with advanced cancer. We have previously reported that IL-18 was strong prognostic factor in aggressive lymphoma patients who received CHOP without rituximab (ASH 2004, abstract #4543). The aim of the present study is to re-assess the prognostic significance of serum IL-18 in DLBCL treated with rituximab, and we also assessed IL-18 with subtype of DLBCL, GCB type and non GCB type. Meterials and methods: Consecutive 154 previously untreated patients with DLBCL prospectively participated in this study between 2002 and 2008. The patients were treated with 6-8 cycles of R-CHOP or R-THP (pirarubicin) -COP regimens. There was no difference with CHOP and THP-COP in our recent prospective randomized study (Tsurumi H et. al. JCRCO 2004). Serum IL-18 was determined by ELISA, and we classified subgroups of DLBCL according to Hans et al. Results: In all patients with DLBCL, the mean ± SD of serum IL-18 level was 829.5±1280.8 pg/ml (range 56 - 8697.5) with a median of 415.8 pg/ml. Various poor prognostic features, such as poor PS, many extranodal sites, advanced disease (CS III/IV) increased LDH and elderly people were strongly associated with a high serum IL-18 levels. The median serum IL-18 levels of the different IPI risk groups were as follows: 201pg/ml for the L risk; 361pg/ml for the LI risk; 440pg/ml for the HI risk; 691pg/ml for the H risk, respectively (P<0.0001). A similar result was provided in rivised IPI (219pg/ml for the very good risk; 271 pg/ml for the good risk; 658 pg/ml for the poor risk, respectively P<0.0001). In addition, the serum IL-18 levels were higher in the non-GCB subgroup than in the GCB subgroup (P<0.005). Patients with high IL-18 (500 pg/ml and over) at onset had significantly lower progression free survival (PFS) rates (5-year: 52%), than those with low IL-18 (5-year: 79 %), respectively (P<0.0001). and In both GCB and non-GCB subgroups, patients with high IL-18 had significantly lower progression free survival rates (GCB and low IL-18:5-ys PFS 90%, GCB and high IL-18 %:5-ys PFS 58%, non-GCB and low IL-18:5-ys PFS 65%, non-GCB and high IL-18:5-ys PFS 42% ; P<0.001). Multivariate analysis employing IL-18 and some conventional prognostic factors demonstrated that age, PS and IL-18 for PFS were poor prognostic factors. Conclusion: These results suggest that, in even rituximab era, a high serum IL-18 level predicts a poor prognosis of DLBCL and may be a useful biomarker for selecting appropriate treatment. Upfront high dose chemotherapy might be well indicated for non-GCB type DLBCL patients with serum high IL-18. Disclosures: No relevant conflicts of interest to declare.

Improved Outcome of Elderly Poor-Prognosis DLBCL Patients with 6xCHOP-14 and 8 Applications of Rituximab (R) Given Over An Extended Period: Results of the SMARTE-R-CHOP-14 Trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 592-592 ◽  
Author(s):  
Michael Pfreundschuh ◽  
Gerhard Held ◽  
Samira Zeynalova ◽  
Viola Pöschel ◽  
Andreas Viardot ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Research Funding ◽  
Poor Prognosis ◽  
Extended Period ◽  
Serum Levels ◽  
Tumor Burden ◽  
Pharmacokinetic Analysis ◽  
Infection Prophylaxis ◽  
Dose Dense ◽  
Prognostic Profile

Abstract Abstract 592 Even though CHOP-14 significantly improved the outcome of elderly patients with DLBCL compared to CHOP-21 (Pfreundschuh et al., Blood 2004;104: 634–641), no superiority of dose-dense R-CHOP-14 compared to R-CHOP-21 was observed in two randomized trials (Delarue R et al., Blood 2009;114:169s; Cunningham et al., J Clin Oncol 2011;29:504s). Pharmacokinetics of R-CHOP-14 showed a plateau of R serum levels not until cycle 5 (Reiser et al., Blood 108, 778a, 2006). In order to achieve high R levels early and maintain R serum levels over a prolonged period of time with 8 R applications, in the SMARTE-R-CHOP-14 phase-II study 6 cycles of CHOP-14 chemotherapy were combined with 8 applications of rituximab (375 mg/m2), of which the first 3 applications were given in a dose-dense fashion followed by increasing intervals with the last 3 R administered after the completion of chemotherapy. 200 elderly pts (61 to 80 years) with DLBCL received 6 cycles of 2-weekly CHOP-14 combined with 8 × R on days −4, −1, 10, 29, 57, 99, 155, and 239. Prophylaxis with levofloxacin, acyclovir and cotrimoxazole was mandatory. The primary endpoint was event-free survival (EFS). 306 pts treated within the RICOVER-60 trial with 6xR-CHOP-14 + 2 R (with R given on days 1, 15, 29, 43, 57, 71, 85 and 99) served as control. 99/200 pts were evaluable for this planned interim analysis. Baseline characteristics were well balanced except more IPI high-risk patients in the SMARTE-R-CHOP-14 population (p=0.015) than in the RICOVER-60 population. Despite the worse prognostic profile of the SMARTE-R-CHOP-14 population, grade 3&4 infections decreased from 6.6% to 3.5% per cycle (p=0.009), and therapy-associated deaths from 5.6% to 3% (p=0.482) with intensified infection prophylaxis. Despite a less favorable study population, SMARTE-R-CHOP-14 resulted in a higher CR (84% vs. 78%) and a lower progression (5% vs. 7%) rate. More importantly, despite the worse prognostic profile of the SMART-E-R-CHOP-14 population 3-year outcome was similar to the RICOVER-60 population (EFS: 67.5% [57.9; 77.1] vs. 66.5% [60.9; 72.0]; PFS: 73.2% [64.2; 82.2] vs. 73.2% [64.2; 82.2]; OS: 81.4% [73.6; 89.2] vs. 78.1% [73.2; 83.0]). When the analysis was restricted to poor-prognosis patients (IPI=3-5), 3-year EFS of SMART-E-R-CHOP-14 patients (n=50) was 15.3% better (68.9% vs. 53.6%), PFS was 13.1% (73.0% vs. 59.9%) and OS was 10.8% (77.9% vs. 67.1%) better compared to 123 poor-prognosis RICOVER-60 patients. A pharmacokinetic analysis showed that with the 2-weekly application of rituximab maximal through levels were reached not before the 6th application, while the SMARTE-R schedule was associated with an early maximal rituximab through level (after the 2nd application) and a prolonged period of measurable R serum levels (420 vs. 320 days). We conclude that while kinetics of 8 applications of 2-weekly rituximab appears to be sufficient for optimal results in elderly patients with low tumor burden (and low IPI), the SMART-E-R schedule achieves superior results in patients with high tumor burden (and high IPI). This is probably due to the longer exposure of tumor cells to relevant rituximab serum levels with the SMART-E-R schedule. The results also indicate that a potential advantage of CHOP-14 over CHOP-21 chemotherapy might be compromised by the shorter exposure to rituximab when 8 applications are given every 2 weeks (R-CHOP-14: last application day 99) compared to 3 weeks (R-CHOP-21: last application day 148). Results of the completed SMART-E-R CHOP-14 trial with 200 patients and a detailed statistical analysis will be presented and discussed. Supported by Deutsche Krebshilfe and Roche Disclosures: Pfreundschuh: Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Research Funding.

Role Of Interim,-PET In Poor Prognosis Young Patients With Diffuse Large B Cell Lymphoma At Diagnosis: Data From An Ancillary Study Of a Prospective Randomized Phase III Study (DLCL04) From the Fondazione Italiana Linfomi

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5088-5088
Author(s):  
Luigi Rigacci ◽  
Patrizia Pregno ◽  
Benedetta Puccini ◽  
Andrea Evangelista ◽  
Annalisa Chiappella ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Clinical Characteristics ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Phase Iii ◽  
Ancillary Study ◽  
Interim Pet ◽  
Large B Cell Lymphoma ◽  
Dose Dense

Abstract Introduction The role of interim-PET (i-PET), after two cycles of chemotherapy, in advanced stage Hodgkin's lymphoma is well defined; the same role in diffuse large B cell lymphoma (DLBCL) is still controversial. The Fondazione Italiana Linfomi planned a prospective randomized phase III trial, addressed to young poor prognosis DLBCL patients at the diagnosis, with a 2x2 factorial design aimed at investigating the possible benefit of intensification with R-HDC+ASCT after R-dose-dense chemotherapy delivered at two different level of dose (R-CHOP14/R-MegaCHOP14). During this study an ancillary study was designed to define the prognostic impact of i-PET on progression free survival (PFS) after two cycles of immunochemotherapy in all treatments arms. Patients and methods As described by Vitolo et al (oral communication, abs 688 ASH 2012), patients were stratified according to aa-IPI and randomized at diagnosis to receive: R-CHOP14 x 8 cycles; R-MegaCHOP14 (1200 mg/sqm Cyclophosphamide, 70 mg/sqm Doxorubicin, standard dose Vincristine and Prednisone) x 6; R-CHOP14 x 4 + R-HDC (Rituximab + High Dose Cytarabine + Mitoxantrone + Dexamethasone) followed by BEAM and ASCT; R-MegaCHOP14 x 4 + R-HDC + BEAM and ASCT. G-CSF support was mandatory. Seventeen centers agreed to participate in the study and enrolled patients. All evaluable patients had performed basal PET and i-PET. A visual dichotomous criteria, according to Deauville Criteria (First Consensus Conference, 2009), was used to define the i-PET result. The final response was identified according to 2007 Cheson response criteria. Results From June 2005 to September 2010, 399 patients were randomized in the overall DLCL04 study and 130 were enrolled for the ancillary PET study , 69 in the R-HDC+ASCT and 61 in R dose dense therapy respectively. The clinical characteristics, as in the overall DLCL04 study, were well balanced among the four arms of therapy excluding a selection bias in the group of patients studied with i-PET. The i-PET result was positive in 74 patients and negative in 56 patients, no differences were observed between negative and positive i-PET results according to clinical characteristics and group of treatment. In particular, in R-dose dense arm 27 were negative and 34 positive, in R-HDC+ASCT 29 were negative and 40 positive, according to immunochemotherapy scheme in R-CHOP14 29 were negative and 40 were positive, in MegaCHOP14 27 were negative and 34 were positive. With a median follow-up of 36 months, 3-year PFS and 3-year Overall Survival (OS) rates for the whole series were: 64% (95% CI:59-69) and 79% (95% CI:74-83) respectively. No differences in PFS was reported according to i-PET result. In particular 3-year PFS were 87%(95% CI:75-94) in i-PET negative patients and 76% (95% CI: 65-85) in i-PET positive patients respectively (p: 0.09 The 3-year PFS according to I- PET results in the different treatment arm were: in the R-HDT+ASCT group i-PET negative or i-PET positive patients had a 3-year PFS of 83% (95% CI:63-92) and 79% (95% CI:63-89) respectively; in the R-dose dense i-PET negative or i-PET positive patients had a 3-year PFS of 92% (95% CI:73-98) and 72% (95% CI:54-85) with a p value near the significance (0.07). According to OS, i-PET negative and i-PET positive patients had a 3-year OS of 89%(95% CI:76-95) and 83%(95% CI:72-90) respectively, p=0.219. Conclusions In our multicenter prospective study, addressed to young poor prognosis DLBCL patients at the diagnosis, i-PET, performed after two immunochemotherapy cycles and analyzed with a visual method, is not able to identify two different risk population. To confirm our data, we are planning in the near future a centralized revision of all evaluable PET. In conclusion, our feeling is that the i-PET after two cycles in poor prognosis DLBCL patients is too early to predict a chemorefractory disease and more parameters must be considered to define clinical response in these patients. 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.

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