Journal ArticleDOI
Randomized Phase II study of R-CHOP with or without bortezomib in previously untreated patients with non-germinal center B-cell-like diffuse large B-cell lymphoma
John P. Leonard,Kathryn S. Kolibaba,James A. Reeves,Anil Tulpule,Ian W. Flinn,Tatjana Kolevska,Robert Robles,Christopher R. Flowers,Robert H. Collins,Nicholas J. DiBella,Steven W. Papish,Parameswaran Venugopal,Andrew Horodner,Amir Tabatabai,Julio Hajdenberg,Jaehong Park,Rachel Neuwirth,George Mulligan,Kaveri Suryanarayan,Dixie Lee Esseltine,Sven de Vos +20 more
TLDR
Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.Abstract:
Purpose To evaluate the impact of the addition of bortezomib to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) on outcomes in previously untreated patients with non-germinal center B-cell-like (non-GCB) diffuse large B-cell lymphoma (DLBCL). Patients and Methods After real-time determination of non-GCB DLBCL using the Hans immunohistochemistry algorithm, 206 patients were randomly assigned (1:1; stratified by International Prognostic Index [IPI] score) to six 21-day cycles of standard R-CHOP alone or R-CHOP plus bortezomib 1.3 mg/m2 intravenously on days 1 and 4 (VR-CHOP). The primary end point, progression-free survival (PFS), was evaluated in 183 patients with centrally confirmed non-GCB DLBCL who received one or more doses of study drug (91 R-CHOP, 92 VR-CHOP). Results After a median follow-up of 34 months, with 25% (R-CHOP) and 18% (VR-CHOP) of patients having had PFS events, the hazard ratio (HR) for PFS was 0.73 (90% CI, 0.43 to 1.24) with VR-CHOP ( P = .611). Two-year PFS rates were 77.6% with R-CHOP and 82.0% with VR-CHOP; they were 65.1% versus 72.4% in patients with high-intermediate/high IPI (HR, 0.67; 90% CI, 0.34 to 1.29), and 90.0% versus 88.9% (HR, 0.85; 90% CI, 0.35 to 2.10) in patients with low/low-intermediate IPI. Overall response rate with R-CHOP and VR-CHOP was 98% and 96%, respectively. The overall survival HR was 0.75 (90% CI, 0.38 to 1.45); 2-year survival rates were 88.4% and 93.0%, respectively. In the safety population (100 R-CHOP and 101 VR-CHOP patients), grade ≥ 3 adverse events included neutropenia (53% v 49%), thrombocytopenia (13% v 29%), anemia (7% v 15%), leukopenia (26% v 25%), and neuropathy (1% v 5%). Conclusion Outcomes for newly diagnosed, prospectively enrolled patients with non-GCB DLBCL were more favorable than expected with R-CHOP and were not significantly improved by adding bortezomib.read more
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Journal ArticleDOI
Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma
David M. Kurtz,Florian Scherer,Florian Scherer,Michael C. Jin,Joanne Soo,Alexander F.M. Craig,Mohammad Shahrokh Esfahani,Jacob J. Chabon,Henning Stehr,Chih Long Liu,Robert Tibshirani,Lauren S. Maeda,Neel K. Gupta,Michael S. Khodadoust,Ranjana H. Advani,Ronald Levy,Aaron M. Newman,Ulrich Dührsen,Andreas Hüttmann,Michel Meignan,Rene-Olivier Casasnovas,Jason R. Westin,Mark Roschewski,Wyndham H. Wilson,Gianluca Gaidano,Davide Rossi,Davide Rossi,Maximilian Diehn,Ash A. Alizadeh +28 more
TL;DR: Pretreatment ctDNA levels and molecular responses are independently prognostic of outcomes in aggressive lymphomas, and these risk factors could potentially guide future personalized risk-directed approaches.
Journal ArticleDOI
The International Consensus Classification of Mature Lymphoid Neoplasms: A Report from the Clinical Advisory Committee.
Elias Campo,Elaine S. Jaffe,James R. Cook,Leticia Quintanilla-Martinez,Steven H. Swerdlow,Kenneth C. Anderson,Pierre Brousset,Lorenzo Cerroni,Laurence de Leval,Stephan Dirnhofer,Ahmet Dogan,Andrew L. Feldman,Falko Fend,Jonathan W. Friedberg,Philippe Gaulard,Paolo Ghia,Steven M. Horwitz,Rebecca L. King,Gilles Salles,Jesús F. San Miguel,John F. Seymour,Steven P. Treon,Julie M. Vose,E. Zucca,Ranjana H. Advani,Stephen M. Ansell,Wing Yan Au,Carlos Barrionuevo,P. Leif Bergsagel,Wing C. Chan,Jeffrey I. Cohen,Andrew Davies,Brunangelo Falini,Irene M. Ghobrial,John R. Goodlad,John G. Gribben,Eric D. Hsi,Brad S. Kahl,Won Seog Kim,Shaji Kumar,Ann S. LaCasce,Camille Laurent,Georg Lenz,John J. Leonard,Michael P. Link,Armando López-Guillermo,Maria-Victoria Mateos,Elizabeth Macintyre,Ari Melnick,Franck Morschhauser,Shigeo Nakamura,Marina Narbaitz,Astrid Pavlovsky,Stefano Pileri,Miguel A. Piris,Barbara Pro,S. Vincent Rajkumar,Steve Rozen,Birgit Sander,Laurie H. Sehn,Margaret A. Shipp,Sonali M. Smith,Louis M. Staudt,Catherine Thieblemont,Thomas Tousseyn,Wyndham H. Wilson,Tadashi Yoshino,Pier Luigi Zinzani,Martin Dreyling,David Scott,Jane N. Winter,Andrew D. Zelenetz +71 more
TL;DR: The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined and some categories considered provisional are now upgraded to definite entities in the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.
Journal ArticleDOI
Diffuse large B-cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment
Yang Liu,Stefan K. Barta +1 more
TL;DR: Diffuse large B‐cell lymphoma is the most common type of aggressive non‐Hodgkin lymphoma originating from the germinal center, and it represents a heterogeneous group of diseases with variable outcomes that are differentially characterized by clinical features, cell of origin (COO), molecular features, and most recently, frequently recurring mutations.
Journal ArticleDOI
Dose-Adjusted EPOCH-R Compared With R-CHOP as Frontline Therapy for Diffuse Large B-Cell Lymphoma: Clinical Outcomes of the Phase III Intergroup Trial Alliance/CALGB 50303
Nancy L. Bartlett,Wyndham H. Wilson,Sin-Ho Jung,Eric D. Hsi,Matthew J. Maurer,Levi Pederson,Mei Yin C. Polley,Brandelyn N. Pitcher,Bruce D. Cheson,Brad S. Kahl,Jonathan W. Friedberg,Louis M. Staudt,Nina D. Wagner-Johnston,Kristie A. Blum,Jeremy S. Abramson,Nishitha Reddy,Jane N. Winter,Julie E. Chang,Ajay K. Gopal,Amy Chadburn,Susan Mathew,Richard I. Fisher,Kristy L. Richards,Heiko Schöder,Andrew D. Zelenetz,John P. Leonard +25 more
TL;DR: In the 50303 study population, the more intensive, infusional DA-EPOCH-R was more toxic and did not improve PFS or OS compared with R-CHOP, suggesting a potential patient selection bias and may preclude generalizability of results to specific risk subgroups.
Journal ArticleDOI
Diffuse Large B-Cell Lymphoma.
Laurie H. Sehn,Gilles Salles +1 more
TL;DR: Diffuse Large B-Cell Lymphoma DLBCL, an aggressive cancer, accounts for about 30% of all lymphomas and empirical combination chemotherapy cures about 65% of patients initially, with another 20 to 25%...
References
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Journal ArticleDOI
Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling
Ash A. Alizadeh,Michael B. Eisen,R. Eric Davis,Izidore S. Lossos,Andreas Rosenwald,Jennifer C. Boldrick,Hajeer Sabet,Truc Tran,Xin Yu,John Powell,Liming Yang,Gerald E. Marti,Troy Moore,James I. Hudson,Li-Sheng Lu,David B. Lewis,Robert Tibshirani,Gavin Sherlock,Wing C. Chan,Timothy C. Greiner,Dennis D. Weisenburger,James O. Armitage,Roger A. Warnke,Ronald Levy,Wyndham H. Wilson,M. R. Grever,John C. Byrd,David Botstein,Patrick O. Brown,Louis M. Staudt +29 more
TL;DR: It is shown that there is diversity in gene expression among the tumours of DLBCL patients, apparently reflecting the variation in tumour proliferation rate, host response and differentiation state of the tumour.
Journal ArticleDOI
Revised response criteria for malignant lymphoma
Bruce D. Cheson,Beate Pfistner,Malik E. Juweid,Randy D. Gascoyne,Lena Specht,Sandra J. Horning,Bertrand Coiffier,Richard I. Fisher,Anton Hagenbeek,Emanuele Zucca,Steven T. Rosen,Sigrid Stroobants,T. Andrew Lister,Richard T. Hoppe,Martin Dreyling,Kensei Tobinai,Julie M. Vose,Joseph M. Connors,Massimo Federico,Volker Diehl +19 more
TL;DR: New guidelines incorporating PET, IHC, and flow cytometry for definitions of response in non-Hodgkin's and Hodgkin's lymphoma are presented and it is hoped that they will be adopted widely by study groups, pharmaceutical and biotechnology companies, and regulatory agencies to facilitate the development of new and more effective therapies to improve the outcome of patients with lymphoma.
Journal ArticleDOI
Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray
Christine P. Hans,Dennis D. Weisenburger,Timothy C. Greiner,Randy D. Gascoyne,Jan Delabie,German Ott,H. Konrad Muller-Hermelink,Elias Campo,Rita M. Braziel,Elaine S. Jaffe,Zenggang Pan,Pedro Farinha,Lynette M. Smith,Brunangelo Falini,Alison H. Banham,Andreas Rosenwald,Louis M. Staudt,Joseph M. Connors,James O. Armitage,Wing C. Chan +19 more
TL;DR: In summary, immunostains can be used to determine the GCB and non-GCB subtypes of DLBCL and predict survival similar to the cDNA microarray.
Journal ArticleDOI
The Use of Molecular Profiling to Predict Survival after Chemotherapy for Diffuse Large-B-Cell Lymphoma
Andreas Rosenwald,George E. Wright,Wing C. Chan,Wing C. Chan,Joseph M. Connors,Elias Campo,Richard I. Fisher,Randy D. Gascoyne,H. Konrad Muller-Hermelink,Erlend B. Smeland,Jena M. Giltnane,Elaine M. Hurt,Hong Zhao,Lauren Averett,Liming Yang,Wyndham H. Wilson,Elaine S. Jaffe,Richard M. Simon,Richard D. Klausner,John Powell,P L Duffey,Dan L. Longo,Timothy C. Greiner,Dennis D. Weisenburger,Warren G. Sanger,Bhavana J. Dave,James C. Lynch,Julie M. Vose,James O. Armitage,Emilio Montserrat,Armando López-Guillermo,Thomas M. Grogan,Thomas P. Miller,Michel Leblanc,German Ott,Stein Kvaløy,Jan Delabie,Harald Holte,Peter Krajci,Trond Stokke,Louis M. Staudt +40 more
TL;DR: DNA microarrays can be used to formulate a molecular predictor of survival after chemotherapy for diffuse large-B-cell lymphoma and this gene-based predictor and the international prognostic index were independent prognostic indicators.
Journal ArticleDOI
Stromal gene signatures in large-B-cell lymphomas
Georg Lenz,George E. Wright,Sandeep S. Dave,Wenming Xiao,Jonathan D. Powell,Hong Zhao,Weihong Xu,Bruce K. Tan,Neta Goldschmidt,Javeed Iqbal,Julie M. Vose,Martin Bast,Kai Fu,Dennis D. Weisenburger,Timothy C. Greiner,James O. Armitage,Alastair H. Kyle,Lorraine May,Randy D. Gascoyne,Joseph M. Connors,Gunhild Trøen,Harald Holte,Stein Kvaløy,Daan Dierickx,Gregor Verhoef,Jan Delabie,Erlend B. Smeland,Pedro Jares,A. Martinez,Armando López-Guillermo,Emili Montserrat,Elias Campo,Rita M. Braziel,Thomas P. Miller,Lisa M. Rimsza,James R. Cook,Brad Pohlman,John Sweetenham,Raymond R. Tubbs,Richard I. Fisher,Elena Hartmann,Andreas Rosenwald,German Ott,German Ott,H-K Muller-Hermelink,D Wrench,T. A. Lister,Elaine S. Jaffe,Wyndham H. Wilson,Wing C. Chan,Louis M. Staudt +50 more
TL;DR: Survival after treatment of diffuse large-B-cell lymphoma is influenced by differences in immune cells, fibrosis, and angiogenesis in the tumor microenvironment, and a multivariate model created from three gene-expression signatures predicted survival both in patients who received CHOP and patients who receive R-CHOP.
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Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling
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