Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial

Delarue, Richard; Tilly, Hervé; Mounier, Nicolas; Petrella, Tony; Salles, Gilles; Thiéblemont, Catherine; Bologna, Serge; Ghesquières, Hervé; Hacini, Maya; Fruchart, Christophe; Ysebaert, Loïc; Fermé, Christophe; Casasnovas, Olivier; Hoof, A. van; Thyss, A.; Delmer, Alain; Fitoussi, Olivier; Molina, Thierry Jo; Haı̈oun, Corinne; Bosly, André

doi:10.1016/s1470-2045(13)70122-0

Cited by 265 publications

(195 citation statements)

References 22 publications

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“…80,81 Indeed, a number of factors should be considered (1) there is no linear dose-effect relation for RTX (in contrast to responses to CHOP chemotherapy), (2) the shorter exposure of RTX in the schedule R-CHOP-14 vs. R-CHOP-21 could not fully exploit the potential provided by the 8 doses of RTX, and (3) on the contrary, the longer exposure to RTX in the R-CHOP-21 regimen could be important from the therapeutic point of view, balancing in the R-CHOP-21 schedule the contribution made by dose-dense chemotherapy in CHOP-14. 66 In other words, the optimal schedule for RTX appears to be every 3 weeks, whereas chemotherapy (CHOP) treatment may benefit from the shorter 2 weeks cycles.…”

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confidence: 99%

Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics

Golay

Semenzato

Rambaldi

et al. 2013

mAbs

115

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confidence: 99%

Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics

Golay

Semenzato

Rambaldi

et al. 2013

mAbs

115

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“…However, in time, the relative benefit of dose-dense chemo-immunotherapy has not held up in head-to-head comparisons of standard CHOP-R-21 with CHOP-R-14: Cunningham et al demonstrated similar response rates [ORR, 88 vs. 91% (P<0.139) and CR/unconfirmed CR (CRu), 63 vs. 58% (P<0.183), respectively] and survival outcomes with CHOP-R-14 and CHOP-R-21 (11). These results were corroborated by GELA in elderly patients with DLBCL (12). By contrast, dose intensification with R-ACVBP has demonstrated a significant survival advantage in young patients with low-or low-intermediate-risk disease compared with CHOP-R-21, but with an associated significant increase in toxicity, raising questions of the generalizability of such a regimen (26).…”

Section: Discussionmentioning

confidence: 81%

“…A number of trials have since reported comparable results for cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab every 14 days (CHOP-R-14) vs. CHOP-R-21, suggesting the need for more effective alternative approaches, such as consolidation therapy (11,12). Consolidation with the radioimmunoconjugate 90 Y-ibritumomab tiuxetan ( 90 Y-ibritumomab; Zevalin ® ; Biogen IDEC, Weston, MA, USA and Spectrum Pharmaceuticals, Irvine, CA, USA) has yielded promising responses and survival outcomes in the first-line and salvage settings (2-year PFS and OS rates as high as 85 and 95%, respectively) in NHL, including DLBCL (13)(14)(15)(16)(17)(18)).…”

Section: Introductionmentioning

confidence: 99%

Phase 2 study of CHOP-R-14 followed by 90Y-ibritumomab tiuxetan in patients with previously untreated diffuse large B-cell lymphoma

Karmali¹,

Larson²,

Shammo³

et al. 2017

Molecular and Clinical Oncology

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Abstract. The aim of this open-label, single-center, phase 2 study was to assess the efficacy and safety of dose-dense CHOP-R-14 followed by 90 Y-ibritumomab radioimmunotherapy (RIT) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL). A total of 20 patients, the majority presenting with high-risk characteristics, were enrolled to receive dose-dense cyclophosphamide, doxorubicin, vincristine, prednisone and rituximab every 14 days (CHOP-R-14), followed by 90 Y-ibritumomab tiuxetan consolidation. Sixteen patients completed RIT consolidation (rituximab 250 mg/m 2 on day 1 and day 7, 8, or 9, followed by a single injection of 90 Y-ibritumomab). Complete response (CR) rates of 75 and 95% were observed after treatment with CHOP-R-14 and RIT, respectively; 4 of the 5 patients who achieved a partial response after CHOP-R-14 converted to CR following treatment with RIT. With a median follow-up of 89.7 months, the progression-free and overall survival rates for the cohort were 75 and 85%, respectively. Hematological adverse events were common following CHOP-R-14 and RIT, but they were manageable with treatment interruption. Therefore, this regimen achieved promising survival outcomes in high-risk DLBCL on long term follow-up, with manageable toxicity.

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“…Since the completion of our trial, CHOP combined with rituximab has been shown to be superior to CHOP alone in the treatment of aggressive NHL across all age groups such that R-CHOP has become the standard in patients with DLBCL [22,23]. Moreover, the addition of rituximab to the CHOP regimen appears to negate the effects of increased dose density from a 21-day cycle of CHOP to a 14-day cycle [24,25].…”

Section: Discussionmentioning

confidence: 92%

A phase III randomized trial of high‐dose CEOP + filgrastim versus standard‐dose CEOP in patients with non‐Hodgkin lymphoma: 10‐year follow‐up data: Australasian Leukaemia and Lymphoma Group (ALLG) NHL07 trial

et al. 2014

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on behalf of the ALLG Increasing dose intensity (DI) of chemotherapy for patients with aggressive non-Hodgkin lymphoma (NHL) may improve outcomes at the cost of increased toxicity. This issue was addressed in a randomized trial aiming to double the DI of myelosuppressive drugs. Between 1994 and 1999, 250 patients with previously untreated aggressive NHL were randomized to treatment with six cycles of 3-weekly standard (s) or intensive (i) chemotherapy: s-CEOP-cyclophosphamide 750, epirubicin 75, vincristine 1.4 mg/m 2 all on day 1, and prednisolone 100 mg days 1-5; i-CEOP-cyclophosphamide 1,500, epirubicin 150, vincristine 1.4 mg/m 2 all on day 1, and prednisolone 100 mg days 1-5. Primary endpoint was 5-year overall survival (OS). Relative to s-CEOP patients, i-CEOP patients achieved a 78% increase in the DI of cyclophosphamide and epirubicin. Despite this, there was no significant difference in any outcome: 5-year OS (56.7% i-CEOP; 55.1% s-CEOP; P 5 0.80), 5-year progression free survival (PFS; 41% i-CEOP; 43% s-CEOP; P 5 0.73), 5-year time to progression (TTP; 44% i-CEOP; 47% s-CEOP; P 5 0.72), or complete remission (CR) 1 unconfirmed CR (CRu) rates (53% i-CEOP; 59% s-CEOP; P 5 0.64). Long-term follow up at 10 years also showed no significant differences in OS, PFS, or TTP. The i-CEOP arm had higher rates of febrile neutropenia (70 vs. 26%), hospitalisations, blood product utilisation, haematological and gastrointestinal toxicities, and lower quality of life scores during treatment, although without significant differences 6-month later. In the treatment of aggressive NHL in the prerituximab era, increasing DI did not result in improved outcomes, while at the same time lead to increased toxicity.

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Dose-dense rituximab-CHOP compared with standard rituximab-CHOP in elderly patients with diffuse large B-cell lymphoma (the LNH03-6B study): a randomised phase 3 trial

Cited by 265 publications

References 22 publications

Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics

Lessons for the clinic from rituximab pharmacokinetics and pharmacodynamics

Phase 2 study of CHOP-R-14 followed by 90Y-ibritumomab tiuxetan in patients with previously untreated diffuse large B-cell lymphoma

A phase III randomized trial of high‐dose CEOP + filgrastim versus standard‐dose CEOP in patients with non‐Hodgkin lymphoma: 10‐year follow‐up data: Australasian Leukaemia and Lymphoma Group (ALLG) NHL07 trial

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