Research in context
Evidence before this study
Peripheral T-cell lymphoma is a heterogeneous group of rare, aggressive lymphoproliferative disorders that represent approximately 10–15% of non-Hodgkin lymphoma cases worldwide.
Clinical outcomes for patients with previously untreated peripheral T-cell lymphoma depend upon histological subtype but are typically poor. Most subtypes of peripheral T-cell lymphoma are treated similarly with combination chemotherapy, most commonly cyclophosphamide (C), doxorubicin (H), vincristine (O), and prednisone (P; CHOP) or CHOP-like regimens.
Several of the peripheral T-cell lymphoma subtypes express CD30, most notably systemic anaplastic large cell lymphoma, for which CD30 expression is a hallmark of the diagnosis. Brentuximab vedotin is an antibody–drug conjugate with shown efficacy in the treatment of relapsed or refractory systemic anaplastic large cell lymphoma. Additionally, combination treatment of brentuximab vedotin with CHP (A+CHP) in a phase 1 trial showed encouraging activity and a manageable safety profile. Given the results of brentuximab vedotin monotherapy in the relapsed and refractory systemic anaplastic large cell lymphoma setting, and its tolerability when combined with CHP, the ECHELON-2 trial was designed to assess the efficacy and safety of A+CHP versus CHOP in patients with previously untreated CD30-positive peripheral T-cell lymphoma.
We searched the scientific literature to identify reports of patients with peripheral T-cell lymphoma given brentuximab vedotin or CHOP chemotherapy. We searched PubMed from June 1, 2012, to Oct 01, 2018, using the terms (“ADCETRIS” or “Brentuximab vedotin” or “BV”) AND (“CHOP” OR “CHP”) AND (“PTCL” or “MTCL”) and identified no other clinical trials of brentuximab vedotin in combination with CHP. Additionally, no reports had been published from randomised, prospective, phase 3 clinical trials establishing the superiority of any regimen over CHOP in untreated patients with peripheral T-cell lymphoma.
Added value of this study
Previous trials that have attempted to improve upon CHOP have shown either no or only modest improvements in response rates or progression-free survival, often with high rates of toxicity. To our knowledge, this trial is the first randomised, double-blind study of a targeted drug combination treatment against standard therapy for this indication and is the first reported prospective phase 3 trial in previously untreated patients with peripheral T-cell lymphoma to show an overall survival benefit over CHOP chemotherapy. Our results show that A+CHP improved progression-free survival and overall survival compared with CHOP alone in patients with CD30-positive peripheral T-cell lymphoma. Importantly, these improvements in survival came without an apparent increase in toxicity.
Implications of all the available evidence
We consider these results to be potentially practice-changing and approval was granted in November, 2018, by the US Food and Drug Administration. Regulatory approval is being sought from additional health authorities worldwide for the use of A+CHP in the treatment of patients with previously untreated CD30-positive peripheral T-cell lymphoma.