The ECHELON-2 Trial: 5-year results of a randomized, phase III study of brentuximab vedotin with chemotherapy for CD30-positive peripheral T-cell lymphoma

S. Horwitz, O. A. O'Connor, B. Pro, L. Trümper, S. Iyer, R. Advani, N. L. Bartlett, J. H. Christensen, F. Morschhauser, E. Domingo-Domenech, G. Rossi, W. S. Kim, T. Feldman, T. Menne, D. Belada, Illés, K. Tobinai, K. Tsukasaki, S. P. Yeh, A. ShustovA. Hüttmann, K. J. Savage, S. Yuen, P. L. Zinzani, H. Miao, V. Bunn, K. Fenton, M. Fanale, M. Puhlmann, T. Illidge

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7 Scopus citations

Abstract

Background: For patients with peripheral T-cell lymphoma (PTCL), outcomes using frontline treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like therapy are typically poor. The ECHELON-2 study demonstrated that brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP) exhibited statistically superior progression-free survival (PFS) per independent central review and improvements in overall survival versus CHOP for the frontline treatment of patients with systemic anaplastic large cell lymphoma or other CD30-positive PTCL. Patients and methods: ECHELON-2 is a double-blind, double-dummy, randomized, placebo-controlled, active-comparator phase III study. We present an exploratory update of the ECHELON-2 study, including an analysis of 5-year PFS per investigator in the intent-to-treat analysis group. Results: A total of 452 patients were randomized (1: 1) to six or eight cycles of A+CHP (N = 226) or CHOP (N = 226). At median follow-up of 47.6 months, 5-year PFS rates were 51.4% [95% confidence interval (CI): 42.8% to 59.4%] with A+CHP versus 43.0% (95% CI: 35.8% to 50.0%) with CHOP (hazard ratio = 0.70; 95% CI: 0.53-0.91), and 5-year overall survival (OS) rates were 70.1% (95% CI: 63.3% to 75.9%) with A+CHP versus 61.0% (95% CI: 54.0% to 67.3%) with CHOP (hazard ratio = 0.72; 95% CI: 0.53-0.99). Both PFS and OS were generally consistent across key subgroups. Peripheral neuropathy was resolved or improved in 72% (84/117) of patients in the A+CHP arm and 78% (97/124) in the CHOP arm. Among patients who relapsed and subsequently received brentuximab vedotin, the objective response rate was 59% with brentuximab vedotin retreatment after A+CHP and 50% with subsequent brentuximab vedotin after CHOP. Conclusions: In this 5-year update of ECHELON-2, frontline treatment of patients with PTCL with A+CHP continues to provide clinically meaningful improvement in PFS and OS versus CHOP, with a manageable safety profile, including continued resolution or improvement of peripheral neuropathy.

Original languageEnglish
Pages (from-to)288-298
Number of pages11
JournalAnnals of Oncology
Volume33
Issue number3
DOIs
StatePublished - Mar 2022

Keywords

  • CHOP
  • brentuximab vedotin
  • frontline treatment
  • overall survival
  • peripheral T-cell lymphoma
  • randomized clinical trial

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