Treatment results of CHOP-21, CHOEP-21, MACOP-B and PMitCEBO with and without rituximab in young good-prognosis patients with aggressive lymphomas: Rituximab as an “equalizer” in the MInT (MABTHERA International Trial Group) study

Pfreundschuh, M; Ho, Aloysius; Wolf, Max; Cavallin‐Ståhl, Eva; Pettengell, Ruth; Vášová, Ingrid; Belch, Andrew; Walewski, Jan; Zinzani, PL; Mingrone, Walter; Loeffler, Markus

doi:10.1200/jco.2005.23.16_suppl.6529

Cited by 19 publications

(7 citation statements)

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“…16 Similarly, Pfreundschuh et al 15 observed worse OS for DLBCL patients treated by immunochemotherapy exhibiting bulky tumor. In our study, we found that tumor burden explained a large part of the variability in rituximab exposure, TMTV 0 accounting for 41% of AUC 1 variability.…”

Section: Discussionmentioning

confidence: 94%

“…Rituximab population PK was previously assessed in patients with DLBCL, 13,14 but the influence of tumor burden has never been investigated in these patients despite clinical evidence suggesting worse outcome in those exhibiting bulky tumor. 15,16 The objectives of the present study were therefore to quantify the impact of total metabolic tumor volume (TMTV 0 ) measured on baseline (TMTV 0 ) using 18 F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET/CT) on rituximab PK, concentration-response relationship and prognosis in DLBCL patients treated with standard doses of rituximab, and to propose an individual rituximab dose adjustment according to TMTV 0 .…”

Section: Introductionmentioning

confidence: 99%

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Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a Lymphoma Study Association report

Tout

Casasnovas

Meignan

et al. 2017

Blood

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Key Points• Rituximab exposure decreased as metabolic tumor volume increased, and correlated with metabolic response and survival.• Rituximab dose could be individualized according to metabolic tumor volume to achieve optimal exposure and therefore optimal response.High variability in patient outcome after rituximab-based treatment is partly explained by rituximab concentrations, and pharmacokinetic (PK) variability could be influenced by tumor burden. We aimed at quantifying the influence of baseline total metabolic tumor volume (TMTV 0 ) on rituximab PK and of TMTV 0 and rituximab exposure on outcome in patients with diffuse large B-cell lymphoma (DLBCL). TMTV 0 was measured by 18 F-fluorodeoxyglucosepositron emission tomography-computed tomography in 108 previously untreated DLBCL patients who received four 375 mg/m 2 rituximab infusions every 2 weeks in combination with chemotherapy in 2 prospective trials. A 2-compartment population model allowed describing rituximab PK and calculating rituximab exposure (area under the concentration-time curve; AUC). The association of TMTV 0 and AUC with metabolic response after 4 cycles, as well as progression-free survival (PFS) and overall survival (OS), was assessed using logistic regression and Cox models, respectively. Cutoff values for patient outcome were determined using receiver operating characteristic curve analysis. Exposure to rituximab decreased as TMTV 0 increased (R 2 5 0.41, P < .0001). A high AUC in cycle 1 ( ‡9400 mg 3 h per liter) was associated with better response (odds ratio, 5.56; P 5 .0006) and longer PFS (hazard ratio [HR], 0.38; P 5 .011) and OS (HR, 0.17; P 5 .001).A nomogram for rituximab dose needed to obtain optimal AUC according to TMTV 0 was constructed, and the 375 mg/m 2 classical dose would be suitable for patients with TMTV 0 <281 cm 3 . In summary, rituximab exposure is influenced by TMTV 0 and correlates with response and outcome of DLBCL patients. Dose individualization according to TMTV 0 should be evaluated in prospective studies. These studies were registered at www.clinicaltrials.gov as #NCT00498043 and

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Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a Lymphoma Study Association report

Tout

Casasnovas

Meignan

et al. 2017

Blood

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“…Although follicular lymphoma is slow-growing and current treatments may control the disease for several years, most patients eventually die from the disease or from complications of its treatment. 3,4 Proteasome inhibitors. Two other studies showed that the drug bortezomib (Velcade; Millennium Pharmaceuticals Inc, Cambridge, MA)-which inhibits the proteasome, an enzyme complex that plays an important role in regulating cell function and growth-shrank tumors in nearly half of patients with mantle-cell lymphoma.…”

Section: Other Notable Researchmentioning

confidence: 99%

Clinical Cancer Advances 2005: Major Research Advances in Cancer Treatment, Prevention, and Screening—A Report From the American Society of Clinical Oncology

Herbst

Bajorin

Bleiberg

et al. 2006

JCO

110

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This year, for the first time, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances 2005: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant clinical research presented or published over the past year across all cancer types. ASCO embarked on this project to provide the public, patients, policymakers, and physicians with an accessible summary of the year's most important research advances. While not intended to serve as a comprehensive review, this report provides a year-end snapshot of research that will have the greatest impact on patient care. As you will read, there is much good news from the front lines of cancer research. These pages report on new chemotherapy regimens that sharply reduce the risk of recurrence for very common cancers; the "coming of age" of targeted cancer therapies; promising studies of drugs to prevent cancer; and improvements in quality of life for people living with the disease, among many other advances. Survival rates for cancer are on the rise, increasing from 50% to 64% over the last 30 years. Cancer still exacts an enormous toll, however. Nearly 1.4 million Americans will be diagnosed this year, and some 570,000 will die of the disease. Clearly, more research is needed to find effective therapies for the most stubborn cancer types and stages. We need to know more about the long-term effects of newer, more targeted cancer therapies, some of which need to be taken over long periods of time. And we need to devote far greater attention to tracking and improving the care of the nearly 10 million cancer survivors in the United States today. Despite these and other challenges, the message of this report is one of hope. Through the dedicated, persistent pursuit of clinical research and participation in clinical trials by people with cancer, we steadily uncover new and better ways of treating, diagnosing, and preventing a disease that touches the lives of so many. I want to thank the Editorial Board members, the Specialty Editors, and the ASCO Cancer Communications Committee for their dedicated work to develop this report, and I hope you find it useful.

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“…Further, prior studies evaluating the prognostic implications of MYC in DLBCL have been performed before the use of rituximab. With studies showing improved outcome using rituximab in combination with CHOP (R-CHOP) or CHOP-like therapies in the treatment of DLBCL, [5][6][7][8] the importance of MYC rearrangement status in this population must be reestablished.…”

Section: Introductionmentioning

confidence: 99%

MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy

Savage¹,

Johnson

Ben-Neriah

et al. 2009

Blood

572

457

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Approximately 5% to 10% of diffuse large B-cell lymphomas (DLBCLs) harbor an MYC oncogene rearrangement (MYC ؉ ). The prognostic significance of MYC ؉ DLBCL was determined in an unselected population of patients with newly diagnosed DLBCL treated with rituximab in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy (R-CHOP). Using a Vysis break-apart fluorescence in situ hybridization probe, 12 of 135 (8.8%) cases of MYC ؉ DLBCL were identified that had no defining high-risk features. MYC ؉ DLBCL was associated with an inferior 5-year progression-free survival (66% vs 31%, P ‫؍‬ .006) and overall survival (72% vs 33%, P ‫؍‬ .016). Multivariate analysis confirmed the prognostic importance of MYC for both progression-free survival (hazard ratio ‫؍‬ 3.28; 95% confidence interval, 1.49-7.21, P ‫؍‬ .003) and overall survival (hazard ratio ‫؍‬ 2.98; 95% confidence interval, 1.28-6.95, P ‫؍‬ .011). Cases of MYC ؉ DLBCL also had a higher risk of central nervous system relapse (P ‫؍‬ . IntroductionDiffuse large B-cell lymphomas (DLBCLs) are recognized to be a heterogeneous group of diseases with clinical, morphologic, immunohistochemical, and molecular subtypes defined in the updated World Health Organization (WHO) classification. 1 Further, a new category has been created defined as "borderline cases," which are considered B-cell lymphomas, unclassifiable, with features intermediate between DLBCL and Burkitt lymphoma. 2 Morphologically, these tumors typically have a mixture of medium-to large-sized cells, a high proliferation rate, and 35% to 50% of cases have an 8q24/MYC translocation. 2 However, approximately 5% to 10% of DLBCLs with typical morphology also harbor an MYC rearrangement (herein after referred to as MYC ϩ ), and these cases are considered in the category of DLBCL, not otherwise specified, in the updated WHO classification. 3 There is very little information regarding the prognostic importance of an isolated MYC rearrangement in DLBCL using modern diagnostic criteria. A recent study suggested that MYC gene rearrangements identified by fluorescence in situ hybridization (FISH) in pathologically defined DLBCL patients treated with cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP)-like chemotherapy are associated with an inferior prognosis. 4 However, it is unclear whether there are identifiable clinical or pathologic characteristics that suggest that a case may harbor an MYC rearrangement to prompt evaluation. Further, prior studies evaluating the prognostic implications of MYC in DLBCL have been performed before the use of rituximab. With studies showing improved outcome using rituximab in combination with CHOP (R-CHOP) or CHOP-like therapies in the treatment of DLBCL, 5-8 the importance of MYC rearrangement status in this population must be reestablished.The purpose of this study was 2-fold: (1) to screen an unselected series of patients with DLBCL for MYC rearrangements to determine the frequency of this occurrence and whether there were any pathologic or ...

show abstract

Treatment results of CHOP-21, CHOEP-21, MACOP-B and PMitCEBO with and without rituximab in young good-prognosis patients with aggressive lymphomas: Rituximab as an “equalizer” in the MInT (MABTHERA International Trial Group) study

Cited by 19 publications

References 0 publications

Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a Lymphoma Study Association report

Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a Lymphoma Study Association report

Clinical Cancer Advances 2005: Major Research Advances in Cancer Treatment, Prevention, and Screening—A Report From the American Society of Clinical Oncology

MYC gene rearrangements are associated with a poor prognosis in diffuse large B-cell lymphoma patients treated with R-CHOP chemotherapy

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