DA-EPOCH-R: less toxic than CODOX-M/R-IVAX in high-risk Burkitt lymphoma

Trial results show equal DA-EPOCH-R efficacy to CODOX-M/R-IVAX as first-line treatment in patients, but less toxicity.

DA-EPOCH-R showed significantly fewer complications, transfusions, and hospitalisation nights

Burkitt lymphoma is a (outside of Africa) rare but aggressive form of non-Hodgkin B-cell lymphoma for which the optimal first-line treatment remains to be defined. Treatment with high-dose multi-agent chemotherapy such as R-CODOX-M/R-IVAC is effective (2-year progression-free survival [PFS] of 64–71%), however at the cost of significant toxicity and long hospitalisation1. Treatment with lower intensity, patient dose-adjusted, and continuous DA-EPOCH-R has demonstrated favourable 2-year PFS of 85% and lower toxicity2.

The multicentre, randomised HOVON/SAKK trial (EudraCT2013-004394-27) compared both regimens. The primary objective was to demonstrate improvement in 2-year PFS from 70% with R-CODOX-M/R-IVAC to 85% with DA-EPOCH-R. Prof. Martine Chamuleau (Amsterdam UMC, the Netherlands) presented the first results3.

The study enrolled a total of 89 newly diagnosed patients with high-risk Burkitt lymphoma (18–75 years old). Of note, to confirm the hypothesis, 260 patients were needed, but due to a slow accrual rate and the inability of another cooperative group to participate the trial was closed prematurely. Enrolled participants were randomised to receive 2 cycles of R-CODOX-M/R-IVAX or 6 cycles of DA-EPOCH-R.

Estimated 2-year PFS after a median follow-up of 19.1 months was 76% for the R-CODOX-M/R-IVAX arm versus 70% for the DA-EPOCH-R arm (P=0.38). Estimated 2-year overall survival was comparable in both arms (76% vs 75%, respectively; P=0.85). In addition, the objective response rate (complete metabolic remission) was comparable in both arms (65% vs 66%).

Toxicity was –as expected– lower in the DA-EPOCH-R arm: 84 adverse events occurred in 30 patients versus 129 adverse events in 34 patients in the R-CODOX-M/R-IVAX arm. In addition, patients in the R-CODOX-M/R-IVAX needed significantly more transfusions (both red blood cells and platelets) and had significantly more hospitalisations compared with patients in the DA-EPOCH-R arm (P<0.01). 

Prof. Chamuleau concluded that “R-CODOX-M/R-IVAX and DA-EPOCH-R were comparable effective regarding PFS, overall survival and objective response rate, in this prematurely closed trial. However, DA-EPOCH-R is associated with significantly fewer complications, transfusions, and hospitalisation nights. Based on these results, DA-EPOCH-R seems the preferred regimen for high-risk Burkitt lymphoma patients.”

  1. Barnes JA, et al. Ann Oncol. 2011;22:1859–1864.
  2. Roschewski M, et al. J Clin Oncol. 2020;38:2519–2529.
  3. Chamuleau M, et al. R-CODOX-M/R-IVAC versus dose-adjusted (DA) EPOCH-R in patients with newly diagnosed high-risk Burkitt lymphoma; first results of a multi-center randomized HOVON/SAKK trial. Abstract LB2370. EHA2022 Hybrid Congress, 09–12 June.