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

被引:310
作者
Bartlett, Nancy L. [1 ]
Wilson, Wyndham H. [2 ]
Jung, Sin-Ho [3 ]
Hsi, Eric D. [4 ]
Maurer, Matthew J. [5 ]
Pederson, Levi D. [5 ]
Polley, Mei-Yin C. [5 ]
Pitcher, Brandelyn N. [3 ]
Cheson, Bruce D. [6 ]
Kahl, Brad S. [1 ]
Friedberg, Jonathan W. [7 ]
Staudt, Louis M. [2 ]
Wagner-Johnston, Nina D. [1 ]
Blum, Kristie A. [8 ]
Abramson, Jeremy S. [9 ]
Reddy, Nishitha M. [10 ]
Winter, Jane N. [11 ]
Chang, Julie E. [12 ]
Gopal, Ajay K. [13 ]
Chadburn, Amy [14 ]
Mathew, Susan [14 ]
Fisher, Richard I. [15 ]
Richards, Kristy L. [16 ]
Schoder, Heiko [17 ]
Zelenetz, Andrew D. [17 ]
Leonard, John P. [14 ]
机构
[1] Washington Univ, Sch Med, Campus Box 8056, St Louis, MO 63110 USA
[2] NCI, NIH, Bethesda, MD 20892 USA
[3] Duke Univ, Durham, NC USA
[4] Cleveland Clin, Cleveland, OH 44106 USA
[5] Mayo Clin, Rochester, MN USA
[6] MedStar Georgetown Univ Hosp, Washington, DC USA
[7] Univ Rochester, Rochester, NY USA
[8] Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA
[9] Massachusetts Gen Hosp, Ctr Canc, Boston, MA USA
[10] Vanderbilt Univ, Med Ctr, Nashville, TN USA
[11] Northwestern Univ, Chicago, IL 60611 USA
[12] Univ Wisconsin, Madison, WI USA
[13] Univ Washington, Seattle, WA 98195 USA
[14] Cornell Univ, Coll Med, New York, NY 10021 USA
[15] Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA
[16] Univ N Carolina, Chapel Hill, NC 27515 USA
[17] Mem Sloan Kettering Canc Ctr, 1275 York Ave, New York, NY 10021 USA
基金
美国国家卫生研究院;
关键词
CHEMOTHERAPY PLUS RITUXIMAB; ELDERLY-PATIENTS; GERMINAL CENTER; YOUNG-PATIENTS; MULTICENTER; EXPRESSION; SURVIVAL; MYC; DOXORUBICIN; RISK;
D O I
10.1200/JCO.18.01994
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
PURPOSEAlliance/CALGB 50303 (NCT00118209), an intergroup, phase III study, compared dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) with standard rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as frontline therapy for diffuse large B-cell lymphoma.PATIENTS AND METHODSPatients received six cycles of DA-EPOCH-R or R-CHOP. The primary objective was progression-free survival (PFS); secondary clinical objectives included response rate, overall survival (OS), and safety.RESULTSBetween 2005 and 2013, 524 patients were registered; 491 eligible patients were included in the final analysis. Most patients (74%) had stage III or IV disease; International Prognostic Index (IPI) risk groups included 26% IPI 0 to 1, 37% IPI 2, 25% IPI 3, and 12% IPI 4 to 5. At a median follow-up of 5 years, PFS was not statistically different between the arms (hazard ratio, 0.93; 95% CI, 0.68 to 1.27; P = .65), with a 2-year PFS rate of 78.9% (95% CI, 73.8% to 84.2%) for DA-EPOCH-R and 75.5% (95% CI, 70.2% to 81.1%) for R-CHOP. OS was not different (hazard ratio, 1.09; 95% CI, 0.75 to 1.59; P = .64), with a 2-year OS rate of 86.5% (95% CI, 82.3% to 91%) for DA-EPOCH-R and 85.7% (95% CI, 81.4% to 90.2%) for R-CHOP. Grade 3 and 4 adverse events were more common (P < .001) in the DA-EPOCH-R arm than the R-CHOP arm, including infection (16.9% v 10.7%, respectively), febrile neutropenia (35.0% v 17.7%, respectively), mucositis (8.4% v 2.1%, respectively), and neuropathy (18.6% v 3.3%, respectively). Five treatment-related deaths (2.1%) occurred in each arm.CONCLUSIONIn 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. The more favorable results with R-CHOP compared with historical controls suggest a potential patient selection bias and may preclude generalizability of results to specific risk subgroups.
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收藏
页码:1790 / +
页数:11
相关论文
共 31 条
[1]   Cohort Profile: The Lymphoma Specialized Program of Research Excellence (SPORE) Molecular Epidemiology Resource (MER) Cohort Study [J].
Cerhan, James R. ;
Link, Brian K. ;
Habermann, Thomas M. ;
Maurer, Matthew J. ;
Feldman, Andrew L. ;
Syrbu, Sergei I. ;
Thompson, Carrie A. ;
Farooq, Umar ;
Novak, Anne J. ;
Slager, Susan L. ;
Allmer, Cristine ;
Lunde, Julianne J. ;
Macon, William R. ;
Inwards, David J. ;
Johnston, Patrick B. ;
Micallef, Ivana N. M. ;
Nowakowski, Grzegorz S. ;
Ansell, Stephen M. ;
Kay, Neil E. ;
Weiner, George J. ;
Witzig, Thomas E. .
INTERNATIONAL JOURNAL OF EPIDEMIOLOGY, 2017, 46 (06) :1753-+
[2]   Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes (vol 24, pg 679, 2018) [J].
Chapuy, Bjoern ;
Stewart, Chip ;
Dunford, Andrew J. ;
Kim, Jaegil ;
Kamburov, Atanas ;
Redd, Robert A. ;
Lawrence, Mike S. ;
Roemer, Margaretha G. M. ;
Li, Amy J. ;
Ziepert, Marita ;
Staiger, Annette M. ;
Wala, Jeremiah A. ;
Ducar, Matthew D. ;
Leshchiner, Ignaty ;
Rheinbay, Ester ;
Taylor-Weiner, Amaro ;
Coughlin, Caroline A. ;
Hess, Julian M. ;
Pedamallu, Chandra S. ;
Livitz, Dimitri ;
Rosebrock, Daniel ;
Rosenberg, Mara ;
Tracy, Adam A. ;
Horn, Heike ;
van Hummelen, Paul ;
Feldman, Andrew L. ;
Link, Brian K. ;
Novak, Anne J. ;
Cerhan, James R. ;
Habermann, Thomas M. ;
Siebert, Reiner ;
Rosenwald, Andreas ;
Thorner, Aaron R. ;
Meyerson, Matthew L. ;
Golub, Todd R. ;
Beroukhim, Rameen ;
Wulf, Gerald G. ;
Ott, German ;
Rodig, Scott J. ;
Monti, Stefano ;
Neuberg, Donna S. ;
Loeffler, Markus ;
Pfreundschuh, Michael ;
Trumper, Lorenz ;
Getz, Gad ;
Shipp, Margaret A. .
NATURE MEDICINE, 2018, 24 (08) :1290-1291
[3]   Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas [J].
Cheson, BD ;
Horning, SJ ;
Coiffier, B ;
Shipp, MA ;
Fisher, RI ;
Connors, JM ;
Lister, TA ;
Vose, J ;
Grillo-López, A ;
Hagenbeek, A ;
Cabanillas, F ;
Klippensten, D ;
Hiddemann, W ;
Castellino, R ;
Harris, NL ;
Armitage, JO ;
Carter, W ;
Hoppe, R ;
Canellos, GP .
JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (04) :1244-1253
[4]   CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. [J].
Coiffier, B ;
Lepage, E ;
Brière, J ;
Herbrecht, R ;
Tilly, H ;
Bouabdallah, R ;
Morel, P ;
Van den Neste, E ;
Salles, G ;
Gaulard, P ;
Reyes, F ;
Gisselbrecht, C .
NEW ENGLAND JOURNAL OF MEDICINE, 2002, 346 (04) :235-242
[5]   Outcomes in refractory diffuse large B-cell lymphoma: results from the international SCHOLAR-1 study [J].
Crump, Michael ;
Neelapu, Sattva S. ;
Farooq, Umar ;
Van den Neste, Eric ;
Kuruvilla, John ;
Westin, Jason ;
Link, Brian K. ;
Hay, Annette ;
Cerhan, James R. ;
Zhu, Liting ;
Boussetta, Sami ;
Feng, Lei ;
Maurer, Matthew J. ;
Navale, Lynn ;
Wiezorek, Jeff ;
Go, William Y. ;
Gisselbrecht, Christian .
BLOOD, 2017, 130 (16) :1800-1808
[6]   Dose-adjusted EPOCH-R (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) in untreated aggressive diffuse large B-cell lymphoma with MYC rearrangement: a prospective, multicentre, single-arm phase 2 study [J].
Dunleavy, Kieron ;
Fanale, Michelle A. ;
Abramson, Jeremy S. ;
Noy, Ariela ;
Caimi, Paolo Fabrizio ;
Pittaluga, Stefania ;
Parekh, Samir ;
Lacasce, Ann ;
Hayslip, John W. ;
Jagadeesh, Deepa ;
Nagpal, Sunil ;
Lechowicz, Mary Jo ;
Gaur, Rakesh ;
Lucas, Andrea ;
Melani, Christopher ;
Roschewski, Mark ;
Steinberg, Seth M. ;
Jaffe, Elaine S. ;
Kahl, Brad ;
Friedberg, Jonathan W. ;
Little, Richard F. ;
Bartlett, Nancy L. ;
Wilson, Wyndham H. .
LANCET HAEMATOLOGY, 2018, 5 (12) :E609-E617
[7]   Dose-Adjusted EPOCH-Rituximab Therapy in Primary Mediastinal B-Cell Lymphoma [J].
Dunleavy, Kieron ;
Pittaluga, Stefania ;
Maeda, Lauren S. ;
Advani, Ranjana ;
Chen, Clara C. ;
Hessler, Julie ;
Steinberg, Seth M. ;
Grant, Cliona ;
Wright, George ;
Varma, Gaurav ;
Staudt, Louis M. ;
Jaffe, Elaine S. ;
Wilson, Wyndham H. .
NEW ENGLAND JOURNAL OF MEDICINE, 2013, 368 (15) :1408-1416
[8]   Long-term results of the R-CHOP study in the treatment of elderly patients with diffuse large B-cell lymphoma:: A study by the groupe d'Etude des lymphomes de l'adulte [J].
Feugier, P ;
Van Hoof, A ;
Sebban, C ;
Solal-Celigny, P ;
Bouabdallah, R ;
Fermé, C ;
Christian, B ;
Lepage, E ;
Tilly, H ;
Morschhauser, F ;
Gaulard, P ;
Salles, G ;
Bosly, A ;
Gisselbrecht, C ;
Reyes, F ;
Coiffier, B .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (18) :4117-4126
[9]   Outcomes of adults and children with primary mediastinal B-cell lymphoma treated with dose-adjusted EPOCH-R [J].
Giulino-Roth, Lisa ;
O'Donohue, Tara ;
Chen, Zhengming ;
Bartlett, Nancy L. ;
LaCasce, Ann ;
Martin-Doyle, William ;
Barth, Matthew J. ;
Davies, Kimberly ;
Blum, Kristie A. ;
Christian, Beth ;
Casulo, Carla ;
Smith, Sonali M. ;
Godfrey, James ;
Termuhlen, Amanda ;
Oberley, Matthew J. ;
Alexander, Sarah ;
Weitzman, Sheila ;
Appel, Burton ;
Mizukawa, Benjamin ;
Svoboda, Jakub ;
Afify, Zeinab ;
Pauly, Melinda ;
Dave, Hema ;
Gardner, Rebecca ;
Stephens, Deborah M. ;
Zeitler, William A. ;
Forlenza, Christopher ;
Levine, Jennifer ;
Williams, Michael E. ;
Sima, Jody L. ;
Bollard, Catherine M. ;
Leonard, John P. .
BRITISH JOURNAL OF HAEMATOLOGY, 2017, 179 (05) :739-747
[10]   Succeeding in Breaking the R-CHOP Ceiling in DLBCL: Learning From Negative Trials [J].
Goy, Andre .
JOURNAL OF CLINICAL ONCOLOGY, 2017, 35 (31) :3519-+