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Erschienen in: memo - Magazine of European Medical Oncology 4/2016

01.12.2016 | short review

DA-EPOCH-R: An alternative treatment for high-risk diffuse large B cell lymphoma?

Treatment intensity and outcome in newly diagnosed myeloma patients

verfasst von: Michael Panny, Thomas Nösslinger

Erschienen in: memo - Magazine of European Medical Oncology | Ausgabe 4/2016

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Summary

Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma with an annual incidence of 7–8 cases per 100,000 per year. With standard induction therapy comprising rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R/CHOP), 40% of all patients get cured. Patients relapsing or being refractory to R/CHOP have a poor prognosis with a 10 % cure rate. On the other hand, the prognosis for patients with an event-free survival of 24 months is excellent. Despite the possibility of identifying patients at high risk for R/CHOP failure at the time of diagnosis, to date, an adequate risk-adapted induction has not been established. Dose-adjusted application of rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (DA-EPOCH-R) is a pharmacodynamic approach to improve R/CHOP by the addition of etoposide, prolonged exposure to chemotherapy agents (continuous infusion of etoposide, vincristine, and doxorubicin over 96 h) and dose adjustment based on the absolute neutrophil count nadir. DA-EPOCH-R has shown promising results in retrospective analyses of various high-risk DLBCL cases. The following article reviews various approaches to define and to treat patients with high-risk DLBCL with a focus on treatment with DA-EPOCH-R.
Literatur
1.
Zurück zum Zitat Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patents in the LNH-98.5 trial, the first randomized study comparing rituximab CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d Etudes des Lymphomes de l Adulte. Blood. 2010;116:2040.CrossRef Coiffier B, Thieblemont C, Van Den Neste E, et al. Long-term outcome of patents in the LNH-98.5 trial, the first randomized study comparing rituximab CHOP to standard CHOP chemotherapy in DLBCL patients: a study by the Groupe d Etudes des Lymphomes de l Adulte. Blood. 2010;116:2040.CrossRef
2.
Zurück zum Zitat Maurer MJ, Ghesquières H, Jais J‑P. Event-Free Survival at 24 Months Is a Robust End Point for Disease-Related Outcome in Diffuse Large B‑Cell Lymphoma Treated With Immunochemotherapy. J Clin Oncol. 2014;32(10):1066–73.CrossRef Maurer MJ, Ghesquières H, Jais J‑P. Event-Free Survival at 24 Months Is a Robust End Point for Disease-Related Outcome in Diffuse Large B‑Cell Lymphoma Treated With Immunochemotherapy. J Clin Oncol. 2014;32(10):1066–73.CrossRef
3.
Zurück zum Zitat Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B‑cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184.CrossRef Gisselbrecht C, Glass B, Mounier N, et al. Salvage regimens with autologous transplantation for relapsed large B‑cell lymphoma in the rituximab era. J Clin Oncol. 2010;28(27):4184.CrossRef
4.
Zurück zum Zitat Zhou Z, Sehn LH, Rademaker AW, Gordon LI, et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B‑cell lymphoma treated in the rituximab era. Blood. 2014;123(6):837–42.CrossRef Zhou Z, Sehn LH, Rademaker AW, Gordon LI, et al. An enhanced International Prognostic Index (NCCN-IPI) for patients with diffuse large B‑cell lymphoma treated in the rituximab era. Blood. 2014;123(6):837–42.CrossRef
5.
Zurück zum Zitat Meyer PN, Fu K, Greiner TC, et al. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B‑cell lymphoma treated with rituximab. J Clin Oncol. 2011;29(2):200–7.CrossRef Meyer PN, Fu K, Greiner TC, et al. Immunohistochemical methods for predicting cell of origin and survival in patients with diffuse large B‑cell lymphoma treated with rituximab. J Clin Oncol. 2011;29(2):200–7.CrossRef
6.
Zurück zum Zitat Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B‑cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275–82.CrossRef Hans CP, Weisenburger DD, Greiner TC, et al. Confirmation of the molecular classification of diffuse large B‑cell lymphoma by immunohistochemistry using a tissue microarray. Blood. 2004;103(1):275–82.CrossRef
7.
Zurück zum Zitat de Jong D, Rosenwald A, Chhanabhai M, et al. Lunenburg Lymphoma Biomarker Consortium. Immunohistochemical prognostic markers in diffuse large B‑cell lymphoma: validation of tissue microarray as a prerequisite for broad clinical applications – a study from the Lunenburg Lymphoma Biomarker Consortium. J Clin Oncol. 2007;25(7):805–12.CrossRef de Jong D, Rosenwald A, Chhanabhai M, et al. Lunenburg Lymphoma Biomarker Consortium. Immunohistochemical prognostic markers in diffuse large B‑cell lymphoma: validation of tissue microarray as a prerequisite for broad clinical applications – a study from the Lunenburg Lymphoma Biomarker Consortium. J Clin Oncol. 2007;25(7):805–12.CrossRef
8.
Zurück zum Zitat Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B‑cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–11.CrossRef Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B‑cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–11.CrossRef
9.
Zurück zum Zitat Rosenwald A, Wright G, Chan WC, et al. Lymphoma/Leukemia Molecular Profiling Project. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(25):1937–47.CrossRef Rosenwald A, Wright G, Chan WC, et al. Lymphoma/Leukemia Molecular Profiling Project. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(25):1937–47.CrossRef
10.
Zurück zum Zitat Lenz G, Wright G, Dave SS, et al. Lymphoma/Leukemia Molecular Profiling Project. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008;359(22):2313–23.CrossRef Lenz G, Wright G, Dave SS, et al. Lymphoma/Leukemia Molecular Profiling Project. Stromal gene signatures in large-B-cell lymphomas. N Engl J Med. 2008;359(22):2313–23.CrossRef
11.
Zurück zum Zitat Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med. 2010;362(15):1417–29.CrossRef Lenz G, Staudt LM. Aggressive lymphomas. N Engl J Med. 2010;362(15):1417–29.CrossRef
12.
Zurück zum Zitat Pasqualucci L. The genetic basis of diffuse large B‑cell lymphoma. Curr Opin Hematol. 2013;20(4):336–44.CrossRef Pasqualucci L. The genetic basis of diffuse large B‑cell lymphoma. Curr Opin Hematol. 2013;20(4):336–44.CrossRef
13.
Zurück zum Zitat Roschewski M, Staudt LM. Wilson WH Diffuse large B‑cell lymphoma-treatment approaches in the molecular era. Nat Rev Clin Oncol. 2014;11(1):12–23.CrossRef Roschewski M, Staudt LM. Wilson WH Diffuse large B‑cell lymphoma-treatment approaches in the molecular era. Nat Rev Clin Oncol. 2014;11(1):12–23.CrossRef
14.
Zurück zum Zitat Barrans S, Crouch S, Smith A, et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B‑cell lymphoma treated in the era of rituximab. J Clin Oncol. 2010;28(20):3360–5.CrossRef Barrans S, Crouch S, Smith A, et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B‑cell lymphoma treated in the era of rituximab. J Clin Oncol. 2010;28(20):3360–5.CrossRef
15.
Zurück zum Zitat Savage KJ, Johnson NA, Ben-Neriah S, et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B‑cell lymphoma patients treated with R‑CHOP chemotherapy. Blood. 2009;114(17):3533–7.CrossRef Savage KJ, Johnson NA, Ben-Neriah S, et al. MYC gene rearrangements are associated with a poor prognosis in diffuse large B‑cell lymphoma patients treated with R‑CHOP chemotherapy. Blood. 2009;114(17):3533–7.CrossRef
16.
Zurück zum Zitat Friedberg JW. Double-hit diffuse large B‑cell lymphoma. J Clin Oncol. 2012;30(28):3439–43.CrossRef Friedberg JW. Double-hit diffuse large B‑cell lymphoma. J Clin Oncol. 2012;30(28):3439–43.CrossRef
17.
Zurück zum Zitat Johnson NA, Slack GW, Savage KJ, et al. Concurrent expression of Myc and BCL2 in diffuse large B cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristin and prednisone. J Clin Oncol. 2012;30:3460.CrossRef Johnson NA, Slack GW, Savage KJ, et al. Concurrent expression of Myc and BCL2 in diffuse large B cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristin and prednisone. J Clin Oncol. 2012;30:3460.CrossRef
18.
Zurück zum Zitat Green TM, Young KH, Visco C, et al. Immunhistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone. J Clin Oncol. 2012;30:3460.CrossRef Green TM, Young KH, Visco C, et al. Immunhistochemical double-hit score is a strong predictor of outcome in patients with diffuse large B cell lymphoma treated with rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone. J Clin Oncol. 2012;30:3460.CrossRef
19.
Zurück zum Zitat Hu S, Xu-Monette ZY, Tzankov A, et al. MYC/BCL2 protein coexpression ontributes to the inferior survival of activated B cell subtype of diffuse large B cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program. Blood. 2013;121:4021.CrossRef Hu S, Xu-Monette ZY, Tzankov A, et al. MYC/BCL2 protein coexpression ontributes to the inferior survival of activated B cell subtype of diffuse large B cell lymphoma and demonstrates high-risk gene expression signatures: a report from The International DLBCL Rituximab-CHOP Consortium Program. Blood. 2013;121:4021.CrossRef
20.
Zurück zum Zitat Hertzberg MS, Gandhi MK, Butcher B, et al. Early treatment intensification with R‑ICE chemotherapy followed by autologous stem cell transplantation (ASCT) using Zevalin-BEAM for patients with poor risk dffuse large B‑cell lymphoma (DLBCL) as identified by interim PET/CT scan performed after four cycles of R‑CHOP-14: a multicenter phase II study of the australasian leukaemia lymphoma study group (ALLG). Blood. 2015;126:815. Hertzberg MS, Gandhi MK, Butcher B, et al. Early treatment intensification with R‑ICE chemotherapy followed by autologous stem cell transplantation (ASCT) using Zevalin-BEAM for patients with poor risk dffuse large B‑cell lymphoma (DLBCL) as identified by interim PET/CT scan performed after four cycles of R‑CHOP-14: a multicenter phase II study of the australasian leukaemia lymphoma study group (ALLG). Blood. 2015;126:815.
21.
Zurück zum Zitat Stiff PJ, Unger JM, Cook JR, et al. Autologous transplantation as consolidation for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 2013;369(18):1681.CrossRef Stiff PJ, Unger JM, Cook JR, et al. Autologous transplantation as consolidation for aggressive non-Hodgkin’s lymphoma. N Engl J Med. 2013;369(18):1681.CrossRef
22.
Zurück zum Zitat Schmitz N, Nickelsen M, Ziepert M, et al. Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B‑cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012;13(12):1250–9.CrossRef Schmitz N, Nickelsen M, Ziepert M, et al. Conventional chemotherapy (CHOEP-14) with rituximab or high-dose chemotherapy (MegaCHOEP) with rituximab for young, high-risk patients with aggressive B‑cell lymphoma: an open-label, randomised, phase 3 trial (DSHNHL 2002-1). Lancet Oncol. 2012;13(12):1250–9.CrossRef
23.
Zurück zum Zitat Récher C, Coiffier B, Haioun C, et al. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B‑cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011;378(9806):1858–67.CrossRef Récher C, Coiffier B, Haioun C, et al. Intensified chemotherapy with ACVBP plus rituximab versus standard CHOP plus rituximab for the treatment of diffuse large B‑cell lymphoma (LNH03-2B): an open-label randomised phase 3 trial. Lancet. 2011;378(9806):1858–67.CrossRef
24.
Zurück zum Zitat Gutierrez M, Chabner BA, Pearson D, et al. Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: an 8‑year follow-up of study of EPOCH. J Clin Oncol. 2000;18:3633–42.CrossRef Gutierrez M, Chabner BA, Pearson D, et al. Role of a doxorubicin-containing regimen in relapsed and resistant lymphomas: an 8‑year follow-up of study of EPOCH. J Clin Oncol. 2000;18:3633–42.CrossRef
25.
Zurück zum Zitat Lai G‑M, Chen Y‑N, Mickley LA, et al. P‑glycoprotein expression and schedule dependence of Adriamycin cytotoxicity in human colon carcinoma cell lines. Int J Cancer. 1991;49:696–703.CrossRef Lai G‑M, Chen Y‑N, Mickley LA, et al. P‑glycoprotein expression and schedule dependence of Adriamycin cytotoxicity in human colon carcinoma cell lines. Int J Cancer. 1991;49:696–703.CrossRef
26.
Zurück zum Zitat Dunleavy K, Pittaluga S, Maeda LS, et al. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B‑cell lymphoma. N Engl J Med. 2013;368(15):1408–16.CrossRef Dunleavy K, Pittaluga S, Maeda LS, et al. Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B‑cell lymphoma. N Engl J Med. 2013;368(15):1408–16.CrossRef
27.
Zurück zum Zitat Dunleavy K, Pittaluga S, Shovlin M, et al. Low-intensity therapy in adults with Burkitt’s lymphoma. N Engl J Med. 2013;369(20):1915–25.CrossRef Dunleavy K, Pittaluga S, Shovlin M, et al. Low-intensity therapy in adults with Burkitt’s lymphoma. N Engl J Med. 2013;369(20):1915–25.CrossRef
28.
Zurück zum Zitat Cusack BJ, Young SP, Driskell J, et al. Doxorubicin and doxorubicinol pharmacokinetics and tissue concentrations following bolus injection and continuous infusion of doxorubicin in the rabbit. Cancer Chemother Pharmacol. 1993;32(1):53–8.CrossRef Cusack BJ, Young SP, Driskell J, et al. Doxorubicin and doxorubicinol pharmacokinetics and tissue concentrations following bolus injection and continuous infusion of doxorubicin in the rabbit. Cancer Chemother Pharmacol. 1993;32(1):53–8.CrossRef
29.
Zurück zum Zitat Gharwan H, Lai C, Grant C, et al. Female fertility following dose-adjusted EPOCH-R chemotherapy in primary mediastinal B‑cell lymphomas. Leuk Lymphoma. 2016;57(7):1616–24.CrossRef Gharwan H, Lai C, Grant C, et al. Female fertility following dose-adjusted EPOCH-R chemotherapy in primary mediastinal B‑cell lymphomas. Leuk Lymphoma. 2016;57(7):1616–24.CrossRef
30.
Zurück zum Zitat Hoelzer D, Walewski J, Döhner H, et al. Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial. Blood. 2014;124:3870–9.CrossRef Hoelzer D, Walewski J, Döhner H, et al. Improved outcome of adult Burkitt lymphoma/leukemia with rituximab and chemotherapy: report of a large prospective multicenter trial. Blood. 2014;124:3870–9.CrossRef
31.
Zurück zum Zitat Ribrag V, Koscielny S, Bosq J, et al. Rituximab and dose-dense chemotherapy for adults with Burkitt’s lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016;387(10036):2402–11.CrossRef Ribrag V, Koscielny S, Bosq J, et al. Rituximab and dose-dense chemotherapy for adults with Burkitt’s lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet. 2016;387(10036):2402–11.CrossRef
32.
Zurück zum Zitat Dunleavy K, Fanale M, LaCasce A, et al. Preliminary Report of a Multicenter Prospective Phase II Study of DA-EPOCH-R in MYC-Rearranged Aggressive B‑Cell Lymphoma. Blood. 2014;124(21):395. Dunleavy K, Fanale M, LaCasce A, et al. Preliminary Report of a Multicenter Prospective Phase II Study of DA-EPOCH-R in MYC-Rearranged Aggressive B‑Cell Lymphoma. Blood. 2014;124(21):395.
33.
Zurück zum Zitat Dunleavy K, Pittaluga S, Wayne A, et al. Myc+ aggressive B‑cell lymphomas: novel therapy of untreated Burkitt Lymphoma (BL) and MYC+ diffuse large B‑cell lymphoma (DLBCL) with DA-EPOCH-R. Ann Oncol. 2011;22(Suppl 4):Abstract 71.2011. Dunleavy K, Pittaluga S, Wayne A, et al. Myc+ aggressive B‑cell lymphomas: novel therapy of untreated Burkitt Lymphoma (BL) and MYC+ diffuse large B‑cell lymphoma (DLBCL) with DA-EPOCH-R. Ann Oncol. 2011;22(Suppl 4):Abstract 71.2011.
34.
Zurück zum Zitat Howlett C, Snedecor SJ, Landsburg DJ, et al. Front line dose escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double hit lymphoma: a systematic review and meta-analysis. Br J Haematol. 2015;170:504.CrossRef Howlett C, Snedecor SJ, Landsburg DJ, et al. Front line dose escalated immunochemotherapy is associated with a significant progression-free survival advantage in patients with double hit lymphoma: a systematic review and meta-analysis. Br J Haematol. 2015;170:504.CrossRef
35.
Zurück zum Zitat Petrich AM, Gandhi M, Jovanovic B, et al. Impact of induction regimen and stem cell transplantation on outcomes in double hit lymphoma: a multicenter retrospective analysis. Blood. 2014;124:2354.CrossRef Petrich AM, Gandhi M, Jovanovic B, et al. Impact of induction regimen and stem cell transplantation on outcomes in double hit lymphoma: a multicenter retrospective analysis. Blood. 2014;124:2354.CrossRef
36.
Zurück zum Zitat Oki Y, Noorani M, Lin P, et al. Double hit lymphoma: the MD Anderson Cancer Center clinical experience. Br J Haematol. 2014;166:891.CrossRef Oki Y, Noorani M, Lin P, et al. Double hit lymphoma: the MD Anderson Cancer Center clinical experience. Br J Haematol. 2014;166:891.CrossRef
37.
Zurück zum Zitat Purroy N, Bergua J, Gallur, et al. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B‑cell lymphoma. A phase II study conducted by the Spanish PETHEMA Group. Br J Haematol. 2015;169:188–98.CrossRef Purroy N, Bergua J, Gallur, et al. Long-term follow-up of dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) in untreated patients with poor prognosis large B‑cell lymphoma. A phase II study conducted by the Spanish PETHEMA Group. Br J Haematol. 2015;169:188–98.CrossRef
38.
Zurück zum Zitat Wilson WH, Grossbard ML, Pittaluga S, et al. Dose-adjusted EPOCH chemotherapy for untreated large B‑cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002;99:2685–93.CrossRef Wilson WH, Grossbard ML, Pittaluga S, et al. Dose-adjusted EPOCH chemotherapy for untreated large B‑cell lymphomas: a pharmacodynamic approach with high efficacy. Blood. 2002;99:2685–93.CrossRef
39.
Zurück zum Zitat Wilson WH, Jung SH, Porcu P, et al. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B‑cell lymphoma with analysis of outcome by molecular subtype. Haematologica. 2012;97:758–65.CrossRef Wilson WH, Jung SH, Porcu P, et al. A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B‑cell lymphoma with analysis of outcome by molecular subtype. Haematologica. 2012;97:758–65.CrossRef
Metadaten
Titel
DA-EPOCH-R: An alternative treatment for high-risk diffuse large B cell lymphoma?
Treatment intensity and outcome in newly diagnosed myeloma patients
verfasst von
Michael Panny
Thomas Nösslinger
Publikationsdatum
01.12.2016
Verlag
Springer Vienna
Erschienen in
memo - Magazine of European Medical Oncology / Ausgabe 4/2016
Print ISSN: 1865-5041
Elektronische ISSN: 1865-5076
DOI
https://doi.org/10.1007/s12254-016-0290-4

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