ECHELON-2 — brentuximab raises PTCL outcomes to new levels

Abstract

Lancet https://doi.org/10.1016/S0140-6736(18)32984-2 (2018) Diverse peripheral T cell lymphoma (PTCL) subtypes are usually treated using cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) or similar regimens, with generally poor results. CD30 expression is common in many PTCL subtypes and is pathognomonic of the systemic anaplastic large cell lymphoma (sALCL) subtype. Now, the excellent efficacy of the anti-CD30 antibody–drug conjugate brentuximab vedotin in this context has been demonstrated in the ECHELON-2 trial. In this phase III trial, patients with previously untreated CD30+ PTCL received brentuximab plus cyclophosphamide, doxorubicin and prednisone (A+CHP) or CHOP (n = 226 in both groups); 72% and 68% of patients, respectively, had sALCL. Strikingly, the median progression-free survival duration in the A+CHP group was more than double that in the CHOP group (48.2 months versus 20.8 months; HR 0.71, 95% CI 0.54–0.93; P = 0.011). Importantly, A+CHP treatment reduced the risk of death by 34% (HR 0.66, 95% CI 0.46–0.95; P = 0.024). The efficacy of A+CHP seemed to be greatest in sALCL subgroups and lowest in patients with angioimmunoblastic T cell lymphoma, although these histological subgroup analyses were underpowered. A+CHP had a manageable toxicity profile that was mostly very similar to that of CHOP, with comparable rates of grade ≥3 adverse events (66% versus 65%), treatment discontinuation (6% versus 7%) and treatment-related deaths (3% versus 4%). These results supported approval of A+CHP for the first-line treatment of CD30+ PTCL via the FDA’s Real-Time Oncology Review Pilot Program. Approval was granted on 16 November 2018, <2 weeks after completion of the licence application, thus rapidly transforming a treatment landscape that had for decades remained unchanged. David Killock H a e M atO lO g i c a l c a n c e r