Dose adjusted R-EPOCH and other etoposide-containing regimens in first-line treatment of diffuse large B-cell lymphoma
Abstract
Etoposide is a well-known cytotoxic agent effective in the treatment of B-large cell lymphoma (B-LCL). Currently, there is no consensus regarding the place of etoposide-containing regimens (R-CHOEP, R-ACVBP and DA-R-EPOCH) in front-line treatment of B-LCL. This paper summarizes published data and our own experience regarding the activity and toxicity of these regimens, especially DA-R-EPOCH. Most non-randomized, real-life and retrospective studies suggest that, compared to R-CHOP, DA-R-EPOCH, similarly to other etoposide-containing regimens, has superior antitumor efficacy but is also more toxic. The most important severe side-effects are hematological and infectious, making the regimen unfeasible in unfit patients. However, in fit patients with high-risk features, progression-free survival rates seem improved by 15–20% compared to R-CHOP. In our series of high-risk [age-adjusted International Prognostic Index (aaIPI) 2–3] fit [Eastern Cooperative Oncology Group (ECOG) performance status 0–2]) B-LCL patients older than 60 treated with DA-R-EPOCH, PFS at 2 years was 70%, while it was 53% in a comparable historical cohort treated with R-CHOP. DA-R-EPOCH resulted in more hematological and infectious toxicity, but no treatment-related mortality. In our opinion, DA-R-EPOCH should be considered in newly diagnosed, fit, high-risk patients with B-LCL who are older than 60, provided that there is adequate outpatient supervision, supportive care, and prompt hospital admittance in case of neutropenic fever or other severe toxicities.
References
- Liu Y, Barta SK. Diffuse large B-cell lymphoma: 2019 update on diagnosis, risk stratification, and treatment. Am J Hematol. 2019; 94(5): 604–616.
- Younes A, Sehn LH, Johnson P, et al. PHOENIX investigators. Randomized phase III trial of ibrutinib and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in non-germinal center B-cell diffuse large B-cell lymphoma. J Clin Oncol. 2019; 37(15): 1285–1295.
- Nowakowski GS, Chiappella A, Gascoyne RD, et al. ROBUST: a phase III study of lenalidomide plus R-CHOP versus placebo plus R-CHOP in previously untreated patients with ABC-type diffuse large B-cell lymphoma. J Clin Oncol. 2021; 39(12): 1317–1328.
- National Comperhensive Cancer Network. B-cell lymphomas (version 3.2021). https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf (April 27, 2021).
- https://www.nccn.org/professionals/physician_gls/pdf/b-cell.pdf (April 27, 2021).
- Tilly H, Gomes da Silva M, Vitolo U, et al. ESMO Guidelines Committee. Diffuse large B-cell lymphoma (DLBCL): ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2015; 26(Suppl 5): v116–v125.
- Bašić-Kinda S, Radman I, Dujmović D, et al. R-CHOEP14 in younger high-risk patients with large B cell lymphoma: an effective front-line regimen with cardiac toxicity: a real-life, single-center experience. Ann Hematol. 2021; 100(6): 1517–1524.
- Wilson WH, Bryant G, Bates S, et al. EPOCH chemotherapy: toxicity and efficacy in relapsed and refractory non-Hodgkin's lymphoma. J Clin Oncol. 1993; 11(8): 1573–1582.
- 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): 1408–1416.
- Purroy N, Bergua J, Gallur L, 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(2): 188–198.
- Pejša V, Prka Ž, Lucijanić M, et al. Rituximab with dose-adjusted EPOCH as first-line treatment in patients with highly aggressive diffuse large B-cell lymphoma and autologous stem cell transplantation in selected patients. Croat Med J. 2017; 58(1): 40–48.
- Zhang WH, Li GY, Ma YJ, et al. Reduced-dose EPOCH-R chemotherapy for elderly patients with advanced stage diffuse large B cell lymphoma. Ann Hematol. 2018; 97(10): 1809–1816.
- Dodero A, Guidetti A, Tucci A, et al. Dose-adjusted EPOCH plus rituximab improves the clinical outcome of young patients affected by double expressor diffuse large B-cell lymphoma. Leukemia. 2019; 33(4): 1047–1051.
- Bartlett NL, Wilson WH, Jung SH, et al. 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. J Clin Oncol. 2019; 37(21): 1790–1799.
- Aurer I, Bašić-Kinda S, Dujmović D, et al. DA-R-EPOCH as front-line treatment of elderly patients with high-risk diffuse large B-cell lymphoma (DLBCL): a real-life single-center study. EHA Library 2020: abstract EP1283.
- Dujmović D, Bašić-Kinda S, Živković N, et al. DA-R-EPOCH as front line therapy of older high-risk patients with diffuse large B-cell lymphoma (DLBCL): experiences of the Croatian Cooperative Group for Hematologic Diseases (KroHem) (in Croatian). Lijec Vjesn. 2020; 142(Suppl 4): 5–6.
- Tilly H, Sharman JP, Bartlett N, et al. POLA-R-CHP: polatuzumab vedotin combined with rituximab, cyclophosphamide, doxorubicin, prednisone for patients with previously untreated diffuse large B-cell lymphoma. Hematol Oncol. 2017; 35(S2): 90–91.
- Morschhauser F, Feugier P, Flinn IW, et al. A phase 2 study of venetoclax plus R-CHOP as first-line treatment for patients with diffuse large B-cell lymphoma. Blood. 2021; 137(5): 600–609.
