Brentuximab vedotin plus chemotherapy for the treatment of frontline systemic anaplastic large cell lymphoma subgroup analysis of the ECHELON2 study at 5 years follow-up

Domingo-Domènech E, Pro B, Illidge T, Horwitz S, Trumper L, Iyer S, et al. Blood Cancer J. 2025;15(1):129. doi:10.1038/s41408-025-01329-2.

Introduction

ECHELON2’s extended 5-year data confirm sustained efficacy of brentuximab vedotin + CHP in frontline sALCL treatment, with superior survival compared to CHOP.

Study Type: Phase 3 randomized double-blind trial

Population: Adult patients with untreated CD30+ PTCL (sALCL subgroup)

Intervention: Brentuximab vedotin + CHP vs. CHOP

Outcomes: Progression-free survival, overall survival, remission rates, safety

• Median PFS not reached vs. 29.4 months with CHOP (HR 0.71; P=0.011)
• 5-year OS: 70.1% (A+CHP) vs. 60.9% (CHOP)
• Higher complete remission rate with A+CHP (67% vs. 50%)
• Manageable safety: higher peripheral neuropathy (54% vs. 32%), but mostly low grade and reversible

Context & Related Research

• Horwitz et al., 2019: ECHELON2 primary publication of improved PFS and OS with A+CHP in PTCL including sALCL (PMID:30522922)
• Horwitz et al., 2022: 5-year follow-up confirms durable survival and safety profile (PMID:34921960)
• Domingo-Domènech et al., 2025: Current subgroup 5-year analysis validates long-term benefits in sALCL (PMID:40750774)

Clinical Implications

• Adopt brentuximab vedotin + CHP as frontline standard for sALCL due to sustained survival benefits
• Communicate risks and reversibility of peripheral neuropathy to patients
• Monitor patients longitudinally to manage long-term safety

Strengths & Limitations

Future Directions

Further studies should explore outcomes beyond 5 years, investigate consolidative stem cell transplant benefit post A+CHP, and assess efficacy differences across ALK-positive vs ALK-negative sALCL.

Conclusion

Brentuximab vedotin plus CHP confers durable, superior survival benefits with manageable long-term safety in frontline sALCL at 5 years, supporting its role as the preferred standard of care.

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References

1. Domingo-Domènech E, Pro B, Illidge T, Horwitz S, Trumper L, Iyer S, et al. Blood Cancer J. 2025;15(1):129. doi:10.1038/s41408-025-01329-2.
2. Horwitz et al., 2019. ECHELON2 primary publication of improved PFS and OS with A+CHP in PTCL including sALCL (PMID:30522922).
3. Horwitz et al., 2022. 5-year follow-up confirms durable survival and safety profile (PMID:34921960).
4. Domingo-Domènech et al., 2025. Current subgroup 5-year analysis validates long-term benefits in sALCL (PMID:40750774).