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 D. 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 M. Reddy, Jane N. Winter, Julie E. Chang, Ajay K. Gopal, Amy ChadburnSusan Mathew, Richard I. Fisher, Kristy L. Richards, Heiko Schoder, Andrew D. Zelenetz, John P. Leonard

Research output: Contribution to journalArticle

Abstract

PURPOSE Alliance/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 METHODS Patients 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. RESULTS Between 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. CONCLUSION 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. 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.

Original languageEnglish (US)
Pages (from-to)1790-1799
Number of pages10
JournalJournal of Clinical Oncology
Volume37
Issue number21
DOIs
StatePublished - Jul 20 2019
Externally publishedYes

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Lymphoma, Large B-Cell, Diffuse
Vincristine
Prednisone
Doxorubicin
Cyclophosphamide
Etoposide
Disease-Free Survival
Survival Rate
Therapeutics
Febrile Neutropenia
Mucositis
Selection Bias
Poisons
Rituximab
Patient Selection
Safety
Survival
Infection
Population

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

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. / Bartlett, Nancy L.; Wilson, Wyndham H.; Jung, Sin Ho; Hsi, Eric D.; Maurer, Matthew J.; Pederson, Levi D.; Polley, Mei Yin C.; Pitcher, Brandelyn N.; Cheson, Bruce D.; Kahl, Brad S.; Friedberg, Jonathan W.; Staudt, Louis M.; Wagner-Johnston, Nina D.; Blum, Kristie A.; Abramson, Jeremy S.; Reddy, Nishitha M.; Winter, Jane N.; Chang, Julie E.; Gopal, Ajay K.; Chadburn, Amy; Mathew, Susan; Fisher, Richard I.; Richards, Kristy L.; Schoder, Heiko; Zelenetz, Andrew D.; Leonard, John P.

In: Journal of Clinical Oncology, Vol. 37, No. 21, 20.07.2019, p. 1790-1799.

Research output: Contribution to journalArticle

Bartlett, NL, Wilson, WH, Jung, SH, Hsi, ED, Maurer, MJ, Pederson, LD, Polley, MYC, Pitcher, BN, Cheson, BD, Kahl, BS, Friedberg, JW, Staudt, LM, Wagner-Johnston, ND, Blum, KA, Abramson, JS, Reddy, NM, Winter, JN, Chang, JE, Gopal, AK, Chadburn, A, Mathew, S, Fisher, RI, Richards, KL, Schoder, H, Zelenetz, AD & Leonard, JP 2019, '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', Journal of Clinical Oncology, vol. 37, no. 21, pp. 1790-1799. https://doi.org/10.1200/JCO.18.01994
Bartlett, Nancy L. ; Wilson, Wyndham H. ; Jung, Sin Ho ; Hsi, Eric D. ; Maurer, Matthew J. ; Pederson, Levi D. ; Polley, Mei Yin C. ; Pitcher, Brandelyn N. ; Cheson, Bruce D. ; Kahl, Brad S. ; Friedberg, Jonathan W. ; Staudt, Louis M. ; Wagner-Johnston, Nina D. ; Blum, Kristie A. ; Abramson, Jeremy S. ; Reddy, Nishitha M. ; Winter, Jane N. ; Chang, Julie E. ; Gopal, Ajay K. ; Chadburn, Amy ; Mathew, Susan ; Fisher, Richard I. ; Richards, Kristy L. ; Schoder, Heiko ; Zelenetz, Andrew D. ; Leonard, John P. / 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. In: Journal of Clinical Oncology. 2019 ; Vol. 37, No. 21. pp. 1790-1799.
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title = "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",
abstract = "PURPOSE Alliance/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 METHODS Patients 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. RESULTS Between 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. CONCLUSION 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. 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.",
author = "Bartlett, {Nancy L.} and Wilson, {Wyndham H.} and Jung, {Sin Ho} and Hsi, {Eric D.} and Maurer, {Matthew J.} and Pederson, {Levi D.} and Polley, {Mei Yin C.} and Pitcher, {Brandelyn N.} and Cheson, {Bruce D.} and Kahl, {Brad S.} and Friedberg, {Jonathan W.} and Staudt, {Louis M.} and Wagner-Johnston, {Nina D.} and Blum, {Kristie A.} and Abramson, {Jeremy S.} and Reddy, {Nishitha M.} and Winter, {Jane N.} and Chang, {Julie E.} and Gopal, {Ajay K.} and Amy Chadburn and Susan Mathew and Fisher, {Richard I.} and Richards, {Kristy L.} and Heiko Schoder and Zelenetz, {Andrew D.} and Leonard, {John P.}",
year = "2019",
month = "7",
day = "20",
doi = "10.1200/JCO.18.01994",
language = "English (US)",
volume = "37",
pages = "1790--1799",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "21",

}

TY - JOUR

T1 - Dose-adjusted EPOCH-R compared with R-CHOP as frontline therapy for diffuse large B-cell lymphoma

T2 - Clinical outcomes of the Phase III intergroup trial alliance/CALGB 50303

AU - Bartlett, Nancy L.

AU - Wilson, Wyndham H.

AU - Jung, Sin Ho

AU - Hsi, Eric D.

AU - Maurer, Matthew J.

AU - Pederson, Levi D.

AU - Polley, Mei Yin C.

AU - Pitcher, Brandelyn N.

AU - Cheson, Bruce D.

AU - Kahl, Brad S.

AU - Friedberg, Jonathan W.

AU - Staudt, Louis M.

AU - Wagner-Johnston, Nina D.

AU - Blum, Kristie A.

AU - Abramson, Jeremy S.

AU - Reddy, Nishitha M.

AU - Winter, Jane N.

AU - Chang, Julie E.

AU - Gopal, Ajay K.

AU - Chadburn, Amy

AU - Mathew, Susan

AU - Fisher, Richard I.

AU - Richards, Kristy L.

AU - Schoder, Heiko

AU - Zelenetz, Andrew D.

AU - Leonard, John P.

PY - 2019/7/20

Y1 - 2019/7/20

N2 - PURPOSE Alliance/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 METHODS Patients 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. RESULTS Between 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. CONCLUSION 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. 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.

AB - PURPOSE Alliance/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 METHODS Patients 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. RESULTS Between 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. CONCLUSION 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. 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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