Improved outcome of elderly patients with poor-prognosis diffuse large B-cell lymphoma (DLBCL) after dose-dense rituximab: Results of the DENSE-R-CHOP-14 trial of the German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL)

Pfreundschuh, Michael; Zeynalova, Samira; Poeschel, Viola; Haenel, Matthias W.; Schmitz, N.; Ho, A.; Reiser, Marcel; Loeffler, Markus; Schubert, Jörg

doi:10.1200/jco.2008.26.15_suppl.8508

Cited by 25 publications

(26 citation statements)

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“…In this small group, the PFS at 30 months was 62% and the OS was 81%. These results are difficult to compare with previously published data because the studies that have evaluated biweekly chemotherapy in patients with DLBCL included either only patients older than 60 years [7,8] or patients younger than 60 years with a good prognosis [6]. The comparative LNH93-3 study of the Groupe d'Etude des Lymphomes del'Adulte (GELA) seems suitable for comparing our results in patients with a poor prognosis [18].…”

Section: Discussioncontrasting

confidence: 44%

“…Recently, Pfreundschuh et al [8] reported the superiority in event-free survival of the R-CHOP-14 schedule compared to CHOP-14 for the treatment of 1222 patients older than 60 years with DLBCL. In this randomized study, 81% of the patients treated with R-CHOP-14 attained CR/CRu and achieved an event-free survival at 3 years of 66%.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, the German group communicated the 3 years results of the RICOVER-60 study [8]. This clinical trial in patients with DLBCL older than 60 years compared the efficacy of R-CHOP-14 versus CHOP-14.…”

Section: Introductionmentioning

confidence: 99%

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R‐CHOP‐14 in patients with diffuse large B‐cell lymphoma younger than 70 years: a multicentre, prospective study

Rueda¹,

Sabı́n

Rifà

et al. 2007

Hematological Oncology

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Several studies have shown that adding rituximab to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisolone) or reducing the interval between chemotherapy cycles from 3 weeks to 2 weeks improves survival in patients with diffuse large B‐cell lymphoma (DLBCL). These studies prompted our group (GOTEL) to evaluate prospectively in a pilot study the feasibility and efficacy of R‐CHOP‐14 in patients with DLBCL. Patients (<70 years) with stage II bulky or stage III or IV DLBCL and no significant comorbidities were included in the study. Rituximab was administered on day 1 before chemotherapy. R‐CHOP was given every 14 days. All patients received filgrastim (5 µg/kg) from days 4 to 10. From May 2002 to August 2004, 80 patients were recruited. Median age was 53 years and 58 patients were <60 years. According to the age‐adjusted international prognostic index (aaIPI), 13 patients (16%) had low‐risk disease, 31 (39%) low‐to‐intermediate risk, 27 (34%) high‐to‐intermediate risk and 9 (11%) high‐risk disease. Grade 3–4 neutropenia was observed in 15 patients (17.5%) and grade 3–4 infections in 13 patients (16%). After therapy, 58 patients (73%) achieved CR‐CRu (95% CI: 55–90%). With a median follow‐up of 26 months, progression‐free survival (PFS) and overall survival (OS) at 30 months were 72% and 86%, respectively. Administration of R‐CHOP‐14 is feasible and effective in patients <70 years. Copyright © 2007 John Wiley & Sons, Ltd.

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Section: Discussioncontrasting

confidence: 44%

Section: Discussionmentioning

confidence: 99%

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R‐CHOP‐14 in patients with diffuse large B‐cell lymphoma younger than 70 years: a multicentre, prospective study

Rueda¹,

Sabı́n

Rifà

et al. 2007

Hematological Oncology

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“…If serum levels are important, as has been suggested from a study in relapsed DLBCL, 24 increasing the dose of rituximab would be the appropriate strategy, and early follow-up of the DENSE-R-CHOP-14 trial 25 suggests that this strategy might work in elderly high-risk patients. Some of the most convincing data that pharmacokinetic-based adaptations of the rituximab administration can indeed improve the outcome of patients with an unfavorable rituximab pharmacokinetics come from the results of the SMARTE-R-CHOP-14 trial of the DSHNHL, 26 where elderly patients received 8 doses of rituximab together with 6 doses of CHOP-14 over a period of 240 days. Interestingly, the 3-year OS improvement by 13% in the SMARTE-R-CHOP-14 high-risk population compared with the same population in the RICOVER-60 study was attributable to a 20% improvement in poor-prognosis (IPI 5 3-5) male patients, with an improvement of only 4% in elderly poorprognosis female patients.…”

Section: Discussionmentioning

confidence: 99%

Suboptimal dosing of rituximab in male and female patients with DLBCL

Pfreundschuh

Müller

Zeynalova³

et al. 2014

Blood

127

111

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Key Points• Elderly females have a better outcome than elderly males and a more favorable rituximab pharmacokinetics than all other patients with DLBCL.• Prospective trials aiming at optimizing rituximab dose and schedule are warranted in all DLBCL patients.To determine the effect of gender on outcome, the male hazard ratio for progression-free survival (HR PFS-male ) was determined in patients with diffuse large B-cell lymphoma (DLBCL). In young patients (MapThera International Trial study), HR PFS-male was 1.3 (P 5 .092) without and 1.1 (P 5 .660) with rituximab. In elderly patients (RICOVER-60 study), HR PFS-male was 1.1 (P 5 .348) with CHOP but increased to 1.6 (P 5 .004) with R-CHOP. The similar improvements of outcome in young patients were associated with similar rituximab clearances in young males and females (9.89 vs 10.38 mL/h; P 5 .238), whereas the greater benefit for elderly females was associated with a slower rituximab clearance (8.47 vs 10.59 mL/h; P 5 .005) and hence higher serum levels and longer exposure times, attributable to an age-dependent (P 5 .004) decrease of rituximab clearance in females but not males. Compared with elderly females, all other subgroups had significantly faster rituximab clearances and hence appear to be suboptimally dosed when rituximab is given at 375 mg/m 2 . Although early results of pharmacokinetic-based prospective trials designed to exploit the full therapeutic potential of rituximab suggest that increased doses and/or prolonged exposure times can improve the outcome of elderly males with DLBCL, further studies are warranted that address the optimization of rituximab dose and schedule in all subgroups of DLBCL patients. (Blood. 2014;123(5):640-646)

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“…76 The results of these studies could induce the scientific community to switch from 6 to 8 cycles of RTX in the treatment of DLBCL. The SMARTE-R-CHOP14 study 82 will show us, instead, if it is convenient also to change the schedule of RTX administration. The schedule of RTX use in the study is so characterized: (1) RTX administration times are not simultaneous to the administration of chemotherapy, (2) the first 3 RTX doses are used with an intensive approach (days −4, −1, 10 of the whole treatment period) with the aim of achieving in the shortest time the maximum RTX serum level in terms of trough concentration, (3) subsequent RTX doses (doses [4][5][6][7][8] …”

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confidence: 99%