Background
Prospective phase 3 trial in children/adolescents (<18 years) with stage IA/IIA nodular lymphocyte-predominant Hodgkin lymphoma (nLPHL) (267 registered, 247 evaluable; 2009–2018), testing surgical resection alone or low-intensity, anthracycline-free CVP chemotherapy for unresectable nodal disease — aiming to spare anthracyclines and radiotherapy.
Results
Interventions and follow up: Arm A (resection only): complete lymph-node resection followed by active surveillance (no chemotherapy or radiotherapy); n=78.
Arm B (CVP): 3 cycles cyclophosphamide + vinblastine + prednisone for unresectable nodal disease. CVP-cohort-1 required a negative end-of-treatment 18F-FDG-PET; a 2014 amendment (CVP-cohort-2) used CT/MRI only.
Primary endpoint: 5-year EFS (death, relapse, second malignancy, PET-positivity as events); PFS primary for CVP-cohort-2.
mFollow up: NR (5-year landmark).
Results: Resection-only 5-yr EFS/PFS: 79.5% (6 of 18 relapsers re-entered the CVP arm).
CVP-cohort-1: complete metabolic response 51/82 (62%); 5-yr EFS 56.4%; 5-yr PFS in CMR group 91.3%.
CVP-cohort-2 5-yr PFS: 64.7%.
Arm B (CVP): 3 cycles cyclophosphamide + vinblastine + prednisone for unresectable nodal disease. CVP-cohort-1 required a negative end-of-treatment 18F-FDG-PET; a 2014 amendment (CVP-cohort-2) used CT/MRI only.
Primary endpoint: 5-year EFS (death, relapse, second malignancy, PET-positivity as events); PFS primary for CVP-cohort-2.
mFollow up: NR (5-year landmark).
Results: Resection-only 5-yr EFS/PFS: 79.5% (6 of 18 relapsers re-entered the CVP arm).
CVP-cohort-1: complete metabolic response 51/82 (62%); 5-yr EFS 56.4%; 5-yr PFS in CMR group 91.3%.
CVP-cohort-2 5-yr PFS: 64.7%.
Adverse events
Hematologic: grade 3–4 neutropenia 68.3% during CVP
Treatment-related deaths: none.
Treatment-related deaths: none.
Conclusions
Early-stage pediatric nLPHL can be managed with surgery alone (~80% 5-yr EFS) or with low-intensity, anthracycline-free CVP achieving 91% 5-yr PFS when end-of-treatment PET shows complete metabolic response. This response-adapted, anthracycline- and radiotherapy-free strategy now constitutes the EuroNet-PHL standard of care for stage IA/IIA nLPHL.
Key Limitations
Non-randomized, response/resectability-adapted cohorts rather than randomized arms; the EFS definition counts PET-positivity as an event, lowering apparent EFS; a mid-study amendment dropping end-of-treatment PET created heterogeneous CVP cohorts; modest evaluable N per arm; long accrual (2009–2018) with evolving imaging standards; pediatric-only population.
Clinical Context
nLPHL is an indolent CD20+, B-cell-rich Hodgkin lymphoma variant historically treated with anthracycline-based chemotherapy with or without radiotherapy. This trial establishes de-escalated, anthracycline- and radiotherapy-free management as the EuroNet standard for stage IA/IIA pediatric nLPHL, reducing late toxicity and complementing adult GHSG data in the field-wide move toward minimizing therapy in low-risk nLPHL.