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MegaCHOEP

MegaCHOEP

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Health Atlas ID: 7WEYAWPPYT-0

Projects: GLA - German Lymphoma Alliance

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Creators and Submitter

Creator

Marita Ziepert

Submitter

René Hänsel

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Views: 583

Created: 16th May 2019 at 13:42

Last updated: 16th May 2019 at 13:42

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Studies (1)
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Publications (13)
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GLA - German Lymphoma Alliance

B-cell lymphoma is the most frequent lymphoid neoplasia accounting for one third of all lymphomas. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) is the current treatment standard, leading to high cure rates especially in younger patients. Although the 3-year event-free survival is about 60% even for elderly patients between 60-80 years old, the remainder of patients eventually relapse and the majority die of their disease. The German Non-Hodgkin's Lymphoma Study
...

Programme: NHL

Public web page: https://www.dshnhl.org

Organisms: Homo sapiens

Human Diseases: non-Hodgkin lymphoma, B-cell lymphoma

MegaCHOEP

GLA - German Lymphoma Alliance

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Marita Ziepert

No description specified

Person responsible: René Hänsel

Snapshots: No snapshots

Study type: Not specified

Investigation: MegaCHOEP

Resources: MegaCHOEP Trial Metadata, MegaCHOEP trial data

Created: 17th Apr 2019 at 12:49, Last updated: 16th May 2019 at 14:10

MegaCHOEP Trial Metadata

GLA - German Lymphoma Alliance

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Marita Ziepert

Demographics, reference pathology diagnosis, Outcome (Event-free survival, Progression-free survival, Overall survival)

Submitter: Christoph Beger

Resource type: Result Dataset of Clinical Study

Technology type: Technology Type

Snapshots: No snapshots

Investigation: MegaCHOEP

Study: MegaCHOEP

Organisms: No organisms

Human Diseases: B-cell lymphoma, non-Hodgkin lymphoma

SOPs: No SOPs

Data files: MegaCHOEP Trial Result Metadata (Excel), MegaCHOEP Trial Result Metadata (ODM)

Created: 16th May 2019 at 06:37, Last updated: 2nd Sep 2019 at 09:55

MegaCHOEP trial data

GLA - German Lymphoma Alliance

All contributors

Marita Ziepert

Demographics, reference pathology diagnosis, Outcome (Event-free survival, Progression-free survival, Overall survival)

Submitter: René Hänsel

Resource type: Experimental Assay Type

Technology type: Technology Type

Snapshots: No snapshots

Investigation: MegaCHOEP

Study: MegaCHOEP

Organisms: No organisms

Human Diseases: B-cell lymphoma

SOPs: No SOPs

Data files: MegaCHOEP Trial Result Data (Excel), MegaCHOEP Trial Result Data (ODM), MegaCHOEP Trial Result Data (SPSS)

Created: 20th May 2019 at 11:35, Last updated: 20th May 2019 at 11:35

Progression-Free Survival as a Surrogate End Point for Overall Survival in First-Line Diffuse Large B-Cell Lymphoma: An Individual Patient-Level Analysis of Multiple Randomized Trials (SEAL).

GLA - German Lymphoma Alliance

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Marita Ziepert

Abstract (Expand)

Purpose Overall survival (OS) is the definitive and best-established primary efficacy end point to evaluate diffuse large B-cell lymphoma (DLBCL) therapies, but it requires prolonged follow-up. An … earlier end point assessed post-treatment would expedite clinical trial conduct and accelerate patient access to effective new therapies. Our objective was to formally evaluate progression-free survival (PFS) and PFS at 24 months (PFS24) as surrogate end points for OS in first-line DLBCL. Patients and Methods Individual patient data were analyzed from 7,507 patients from 13 multicenter randomized controlled trials of active treatment in previously untreated DLBCL, published after 2002, with sufficient PFS data to predict treatment effects on OS. Trial-level surrogacy examining the correlation of treatment effect estimates of PFS/PFS24 and OS was evaluated using both linear regression ( R(2)WLS) and Copula bivariable ( R(2)Copula) models. Prespecified criteria for surrogacy required either R(2)WLS or R(2)Copula >/= 0.80 and neither < 0.7, with lower-bound 95% CI > 0.60. Results Trial-level surrogacy for PFS was strong ( R(2)WLS = 0.83; R(2)Copula = 0.85) and met the predefined criteria for surrogacy. At the patient level, PFS strongly correlated with OS. The surrogate threshold effect had a hazard ratio of 0.89. Surrogacy was consistent across comparisons with or without rituximab and with rituximab maintenance trials. Trial-level surrogacy for PFS24 was relatively strong ( R(2)WLS = 0.77; R(2)Copula = 0.78) but did not meet prespecified criteria. At the patient level, PFS24 significantly correlated with OS. The surrogate threshold effect had an odds ratio of 1.51. Conclusion This large pooled analysis of individual patient data supports PFS as a surrogate end point for OS in future randomized controlled trials evaluating chemoimmunotherapy in DLBCL. Use of this end point may expedite therapeutic development with the intent of bringing novel therapies to this patient population years before OS results are mature.

Authors: Q. Shi, N. Schmitz, F. S. Ou, J. G. Dixon, D. Cunningham, M. Pfreundschuh, J. F. Seymour, U. Jaeger, T. M. Habermann, C. Haioun, H. Tilly, H. Ghesquieres, F. Merli, M. Ziepert, R. Herbrecht, J. Flament, T. Fu, B. Coiffier, C. R. Flowers

Date Published: 1st Sep 2018

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

PubMed ID: 29975624

Citation: J Clin Oncol. 2018 Sep 1;36(25):2593-2602. doi: 10.1200/JCO.2018.77.9124. Epub 2018 Jul 5.

Created: 17th Apr 2019 at 14:02, Last updated: 16th May 2019 at 15:12

Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) enrolled on randomized clinical trials.

GLA - German Lymphoma Alliance

All contributors

Marita Ziepert

Abstract (Expand)

Background: Patients with diffuse large B-cell lymphoma treated with first-line anthracycline-based immunochemotherapy and remaining in remission at 2 years have excellent outcomes. This study assessed … overall survival (OS) stratified by progression-free survival (PFS) at 24 months (PFS24) using individual patient data from patients with DLBCL enrolled in multi-center, international randomized clinical trials as part of the Surrogate Endpoint for Aggressive Lymphoma (SEAL) Collaboration. Patients and methods: PFS24 was defined as being alive and PFS24 after study entry. OS from PFS24 was defined as time from identified PFS24 status until death due to any cause. OS was compared with each patient's age-, sex-, and country-matched general population using expected survival and standardized mortality ratios (SMRs). Results: A total of 5853 patients enrolled in trials in the SEAL database received rituximab as part of induction therapy and were included in this analysis. The median age was 62 years (range 18-92), and 56% were greater than 60 years of age. At a median follow-up of 4.4 years, 1337 patients (23%) had disease progression, 1489 (25%) had died, and 5101 had sufficient follow-up to evaluate PFS24. A total of 1423 assessable patients failed to achieve PFS24 with a median OS of 7.2 months (95% CI 6.8-8.1) after progression; 5-year OS after progression was 19% and SMR was 32.1 (95% CI 30.0-34.4). A total of 3678 patients achieved PFS24; SMR after achieving PFS24 was 1.22 (95% CI 1.09-1.37). The observed OS versus expected OS at 3, 5, and 7 years after achieving PFS24 was 93.1% versus 94.4%, 87.6% versus 89.5%, and 80.0% versus 83.7%, respectively. Conclusion: Patients treated with rituximab containing anthracycline-based immunochemotherapy on clinical trials who are alive without progression at 24 months from the onset of initial therapy have excellent outcomes with survival that is marginally lower but clinically indistinguishable from the age-, sex-, and country-matched background population for 7 years after achieving PFS24.

Authors: M. J. Maurer, T. M. Habermann, Q. Shi, N. Schmitz, D. Cunningham, M. Pfreundschuh, J. F. Seymour, U. Jaeger, C. Haioun, H. Tilly, H. Ghesquieres, F. Merli, M. Ziepert, R. Herbrecht, J. Flament, T. Fu, C. R. Flowers, B. Coiffier

Date Published: 1st Aug 2018

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

PubMed ID: 29897404

Citation: Ann Oncol. 2018 Aug 1;29(8):1822-1827. doi: 10.1093/annonc/mdy203.

Created: 17th Apr 2019 at 13:19, Last updated: 16th May 2019 at 14:50

Clinical Impact of the Cell-of-Origin Classification and the MYC/ BCL2 Dual Expresser Status in Diffuse Large B-Cell Lymphoma Treated Within Prospective Clinical Trials of the German High-Grade Non-Hodgkin's Lymphoma Study Group.

GLA - German Lymphoma Alliance

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Michael Hummel

Marita Ziepert

Markus Löffler

Abstract (Expand)

Purpose To explore the prognostic impact and interdependence of the cell-of-origin (COO) classification, dual expression (DE) of MYC and BCL2 proteins, and MYC, BCL2, and BCL6 translocations in two … prospectively randomized clinical trials of patients with diffuse large B-cell lymphoma (DLBCL). Patients and Methods Overall, 452 formalin-fixed paraffin-embedded samples from two prospective, randomized DLBCL trials (RICOVER-60, prospective, randomized study for patients > 60 years, all IPI groups; and R-MegaCHOEP, prospective, randomized study for patients </= 60 years with age-adjusted IPI 2,3) of the German High-Grade Non-Hodgkin Lymphoma Study Group were analyzed with the Lymph2Cx assay for COO classification, with immunohistochemistry for MYC and BCL2, and with fluorescent in situ hybridization for MYC, BCL2, and BCL6 rearrangements. Results COO classification was successful in 414 of 452 samples. No significant differences with respect to COO (activated B-cell [ABC]-like DLBCL v germinal center B-cell [GCB]-like DLBCL) were observed in event-free survival, progression-free survival, and overall survival in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in the RICOVER-60 trial. Also, no differences with respect to COO were observed in multivariable analyses adjusted for International Prognostic Index factors in event-free survival (hazard ratio [HR] of ABC-like disease v GCB-like disease, 1.0; 95% CI, 0.6 to 1.6; P = .93), progression-free survival (HR, 1.1; 95% CI, 0.6 to 1.8; P = .82), and overall survival (HR, 1.0; 95% CI, 0.6 to 1.8; P = .96). Similar results were observed in the R-MegaCHOEP trial. In patients treated with R-CHOP, DE status was associated with significantly inferior survival compared with nonDE within the GCB, but not within the ABC subgroup. DE status was associated with significantly inferior outcome compared with patients with ABC-like DLBCL without DE (5-year PFS rate, 39% [95% CI,19% to 59%] v 68% [95% CI, 52% to 85%]; P = .03) and compared with patients with GCB-like DLBCL without DE. When data from patients with nonDE were analyzed separately, the outcome of patients in the ABC subgroup was inferior to that of patients in the GCB subgroup (5-year PFS rate, 68% [95% CI, 52% to 85%] v 85% [95% CI, 74% to 96%]; P = .04). Conclusion COO profiling in two prospective randomized DLBCL trials failed to identify prognostic subgroups, whereas dual expression of MYC and BCL2 was predictive of poor survival. Evaluation of prognostic or predictive biomarkers in the management of DLBCL, such as the COO, within prospective clinical trials will be important in the future.

Authors: A. M. Staiger, M. Ziepert, H. Horn, D. W. Scott, T. F. E. Barth, H. W. Bernd, A. C. Feller, W. Klapper, M. Szczepanowski, M. Hummel, H. Stein, D. Lenze, M. L. Hansmann, S. Hartmann, P. Moller, S. Cogliatti, G. Lenz, L. Trumper, M. Loffler, N. Schmitz, M. Pfreundschuh, A. Rosenwald, G. Ott

Date Published: 1st Aug 2017

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

PubMed ID: 28525305

Citation: J Clin Oncol. 2017 Aug 1;35(22):2515-2526. doi: 10.1200/JCO.2016.70.3660. Epub 2017 May 19.

Created: 17th Apr 2019 at 14:03, Last updated: 16th May 2019 at 15:14

Frequent NFKBIE deletions are associated with poor outcome in primary mediastinal B-cell lymphoma.

GLA - German Lymphoma Alliance

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Michael Hummel

Marita Ziepert

Abstract (Expand)

We recently reported a truncating deletion in the NFKBIE gene, which encodes IkappaBepsilon, a negative feedback regulator of NF-kappaB, in clinically aggressive chronic lymphocytic leukemia (CLL). … Because preliminary data indicate enrichment of NFKBIE aberrations in other lymphoid malignancies, we screened a large patient cohort (n = 1460) diagnosed with different lymphoid neoplasms. While NFKBIE deletions were infrequent in follicular lymphoma, splenic marginal zone lymphoma, and T-cell acute lymphoblastic leukemia (<2%), slightly higher frequencies were seen in diffuse large B-cell lymphoma, mantle cell lymphoma, and primary central nervous system lymphoma (3% to 4%). In contrast, a remarkably high frequency of NFKBIE aberrations (46/203 cases [22.7%]) was observed in primary mediastinal B-cell lymphoma (PMBL) and Hodgkin lymphoma (3/11 cases [27.3%]). NFKBIE-deleted PMBL patients were more often therapy refractory (P = .022) and displayed inferior outcome compared with wild-type patients (5-year survival, 59% vs 78%; P = .034); however, they appeared to benefit from radiotherapy (P =022) and rituximab-containing regimens (P = .074). NFKBIE aberrations remained an independent factor in multivariate analysis (P = .003) and when restricting the analysis to immunochemotherapy-treated patients (P = .008). Whole-exome sequencing and gene expression profiling verified the importance of NF-kappaB deregulation in PMBL. In summary, we identify NFKBIE aberrations as a common genetic event across B-cell malignancies and highlight NFKBIE deletions as a novel poor-prognostic marker in PMBL.

Authors: L. Mansouri, D. Noerenberg, E. Young, E. Mylonas, M. Abdulla, M. Frick, F. Asmar, V. Ljungstrom, M. Schneider, K. Yoshida, A. Skaftason, T. Pandzic, B. Gonzalez, A. Tasidou, N. Waldhueter, A. Rivas-Delgado, M. Angelopoulou, M. Ziepert, C. M. Arends, L. Couronne, D. Lenze, C. D. Baldus, C. Bastard, J. Okosun, J. Fitzgibbon, B. Dorken, H. G. Drexler, D. Roos-Weil, C. A. Schmitt, H. D. Munch-Petersen, T. Zenz, M. L. Hansmann, J. C. Strefford, G. Enblad, O. A. Bernard, E. Ralfkiaer, M. Erlanson, P. Korkolopoulou, M. Hultdin, T. Papadaki, K. Gronbaek, A. Lopez-Guillermo, S. Ogawa, R. Kuppers, K. Stamatopoulos, N. Stavroyianni, G. Kanellis, A. Rosenwald, E. Campo, R. M. Amini, G. Ott, T. P. Vassilakopoulos, M. Hummel, R. Rosenquist, F. Damm

Date Published: 8th Dec 2016

Publication Type: Not specified

Human Diseases: B-cell lymphoma

PubMed ID: 27670424

Citation: Blood. 2016 Dec 8;128(23):2666-2670. doi: 10.1182/blood-2016-03-704528. Epub 2016 Sep 26.

Created: 17th Apr 2019 at 13:15, Last updated: 16th May 2019 at 14:49

CNS International Prognostic Index: A Risk Model for CNS Relapse in Patients With Diffuse Large B-Cell Lymphoma Treated With R-CHOP.

GLA - German Lymphoma Alliance

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Samira Zeynalova

Marita Ziepert

Markus Löffler

Abstract (Expand)

PURPOSE: To develop and validate a risk score for relapse in the CNS in patients with diffuse large B-cell lymphoma (DLBCL). PATIENTS AND METHODS: A total of 2,164 patients (18 to 80 years old) with … aggressive B-cell lymphomas (80% DLBCL) treated with rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy, who were enrolled in studies from the German High-Grade Non-Hodgkin Lymphoma Study Group and the MabThera International Trial, were analyzed for occurrence of relapse/progression in the CNS. The resulting risk model was validated in an independent data set of 1,597 patients with DLBCL identified in the British Columbia Cancer Agency Lymphoid Cancer database. RESULTS: The risk model consists of the International Prognostic Index (IPI) factors in addition to involvement of kidneys and/or adrenal glands (CNS-IPI). In a three-risk group model, the low-risk group (46% of all patients analyzed), the intermediate-risk group (41%), and the high-risk group (12%) showed 2-year rates of CNS disease of 0.6% (CI, 0% to 1.2%), 3.4% (CI, 2.2% to 4.4%), and 10.2% (CI, 6.3% to 14.1%), respectively. Patients from the validation British Columbia Cancer Agency data set showed similar rates of CNS disease for low-risk (0.8%; CI, 0.0% to 1.6%), intermediate-risk (3.9%; CI, 2.3% to 5.5%), and high-risk (12.0%; CI, 7.9% to 16.1%) groups. CONCLUSION: The CNS-IPI is a robust, highly reproducible tool that can be used to estimate the risk of CNS relapse/progression in patients with DLBCL treated with R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy. Close to 90% of patients with DLBCL belong to the low- and intermediate-risk groups and have a CNS relapse risk < 5%; they may be spared any diagnostic and therapeutic intervention. In contrast, those in the high-risk group have a > 10% risk of CNS relapse and should be considered for CNS-directed investigations and prophylactic interventions.

Authors: N. Schmitz, S. Zeynalova, M. Nickelsen, R. Kansara, D. Villa, L. H. Sehn, B. Glass, D. W. Scott, R. D. Gascoyne, J. M. Connors, M. Ziepert, M. Pfreundschuh, M. Loeffler, K. J. Savage

Date Published: 10th Sep 2016

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

PubMed ID: 27382100

Citation: J Clin Oncol. 2016 Sep 10;34(26):3150-6. doi: 10.1200/JCO.2015.65.6520. Epub 2016 Jul 5.

Created: 17th Apr 2019 at 13:59, Last updated: 16th May 2019 at 15:09

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