Background
Long-term follow-up update of GHSG HD10 (Sasse et al, JCO 2017). 1,370 patients with early favorable Hodgkin lymphoma originally enrolled in the HD10 4-arm factorial trial. Updated analysis at median follow-up of 137 months (11.4 years) to assess whether the non-inferiority of 2 cycles ABVD + 20 Gy IFRT is maintained long-term.
Interventions and follow up
Arm A: ABVD × 4 cycles + IFRT 30 Gy
Arm B: ABVD × 4 cycles + IFRT 20 Gy
Arm C: ABVD × 2 cycles + IFRT 30 Gy
Arm D: ABVD × 2 cycles + IFRT 20 Gy
Primary endpoint: Long-term progression-free and overall survival
mFollow up: 137 months (11.4 years)
Arm B: ABVD × 4 cycles + IFRT 20 Gy
Arm C: ABVD × 2 cycles + IFRT 30 Gy
Arm D: ABVD × 2 cycles + IFRT 20 Gy
Primary endpoint: Long-term progression-free and overall survival
mFollow up: 137 months (11.4 years)
Results
PFS at 10 years: 85% (2 cyc + 20 Gy) vs 86% (4 cyc + 30 Gy)
OS at 10 years: 93.5% (2 cyc + 20 Gy) vs 94.3% (4 cyc + 30 Gy) — non-inferiority maintained
Second malignancy rate: 7.9% (2 cyc + 20 Gy) vs 8.2% (4 cyc + 30 Gy) — not significantly different
OS at 10 years: 93.5% (2 cyc + 20 Gy) vs 94.3% (4 cyc + 30 Gy) — non-inferiority maintained
Second malignancy rate: 7.9% (2 cyc + 20 Gy) vs 8.2% (4 cyc + 30 Gy) — not significantly different
Adverse events
Main adverse events: Late effects including secondary malignancies (leukemia, lymphoma, solid tumors) comparable across arms. No statistically significant difference in cardiovascular events between RT dose groups at this follow-up.
Conclusions
The non-inferiority of 2 cycles ABVD + 20 Gy IFRT is maintained at long-term (11-year) follow-up with equivalent OS and second malignancy rates, confirming this as the durable standard for early favorable Hodgkin lymphoma.
Key Limitations
Key Limitations: Follow-up still insufficient to fully assess lifetime second malignancy risk (particularly breast cancer and cardiovascular events from thoracic RT). Absolute late-effects differences may emerge with longer follow-up. RT technique used (IFRT) is now being replaced by ISRT with smaller fields, potentially reducing long-term toxicity further. PET-guidance (avoiding RT in PET-negative patients) not addressed.
Clinical Context
This update solidifies 2 cycles ABVD + 20 Gy ISRT as a durable standard. The long-term equivalence of second malignancy rates is reassuring but does not negate the ongoing importance of RT-sparing approaches in younger patients or those with high second malignancy risk (e.g., mediastinal RT in women <30).
References