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ACPE Required Forms: PACULit Literature Updates September 2025: Oncology3 Topics
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Lesson 18,
Topic 1
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Brentuximab vedotin plus chemotherapy for the treatment of frontline systemic anaplastic large cell lymphoma
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Daily Literature Update
Brentuximab vedotin plus chemotherapy for the treatment of frontline systemic anaplastic large cell lymphoma
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
Long-term follow-up of frontline sALCL patients shows improved progression-free survival and remission with brentuximab vedotin plus CHP versus standard CHOP chemotherapy.
Study Overview
Study Type: Global, randomized, double-blind phase 3 trial
Population: 452 adults with previously untreated CD30-positive sALCL
Intervention: Brentuximab vedotin + CHP vs CHOP every 3 weeks for 6-8 cycles
Outcome: 5-year progression-free survival (PFS), overall survival (OS), remission rates, safety
Key Findings
- 5-year PFS improved with A+CHP: HR 0.66; 57.1% vs 44.4% with CHOP
- Higher complete remission (70% vs 57%) and objective response rates (83% vs 72%)
- OS trended favorably (HR 0.72), but not statistically significant at 5 years
- Peripheral neuropathy manageable; similar safety profiles
Context & Related Research
- Domingo-Domènech et al., 2025: 5-year subgroup analysis confirms long-term PFS and remission benefits of brentuximab vedotin + CHP in sALCL, with a 34% risk reduction for progression or death (PMID:37150016).
- Original ECHELON2 Phase III Trial: Demonstrated improved PFS and OS for BV+CHP vs CHOP in CD30-positive PTCL, establishing A+CHP as a frontline standard.
- Clinical Consensus: This robust randomized evidence positions brentuximab vedotin plus CHP as preferred first-line treatment for sALCL with a manageable safety profile.
Clinical Implications
- Use brentuximab vedotin + CHP as preferred frontline therapy for untreated CD30+ sALCL.
- Expect improved progression-free survival and higher remission rates versus CHOP.
- Monitor and manage peripheral neuropathy; safety profile remains manageable.
Strengths & Limitations
| Strengths | Limitations |
|---|---|
| Large, phase 3 randomized controlled trial with 5-year follow-up | Subgroup analysis may have limited power for some outcomes (e.g. OS) |
| Multicenter, global enrollment increases generalizability | Did not reach statistical significance for OS at 5 years |
| Robust efficacy endpoints including PFS, remission, and safety | Comparator arm uses vincristine; newer therapies not assessed |
Future Directions
Further research should focus on longer-term overall survival outcomes, quality of life, and neuropathy management strategies, alongside exploration of novel combinations in frontline sALCL therapy.
Conclusion
Brentuximab vedotin plus CHP improves long-term progression-free survival and remission in frontline sALCL with manageable safety, supporting its use as preferred first-line therapy.
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