PACULit Daily Literature Update reviews the 5-year subgroup analysis of the ECHELON-2 trial focusing on frontline treatment for systemic anaplastic large cell lymphoma (sALCL). Hosted discussion covers study design (randomized, double-blind, active-controlled) and the sALCL patient cohort, comparing brentuximab vedotin plus CHP (BV+CHP) to CHOP. Key findings at five years include not reached median progression-free survival for BV+CHP vs 29.4 months for CHOP (hazard ratio 0.71, 95% CI 0.54–0.93; p=0.011), and 5-year overall survival of 70.1% vs 60.9%. The complete remission rate favored BV+CHP (67% vs 50%). Safety signals showed higher peripheral neuropathy with BV+CHP (54% vs 32%, mostly grade 1–2 but reversible) but lower febrile neutropenia (18% vs 31%), possibly reflecting vincristine omission. The episode explains the mechanism of brentuximab vedotin as an antibody-drug conjugate delivering MMAE to CD30-positive cells, and discusses clinical implications, including adopting BV+CHP as frontline standard of care for untreated sALCL, supportive care considerations, and guideline context (NCCN/NICE). Limitations of subgroup analyses and the need for longer-term follow-up are also highlighted.