Background
Phase 3, open-label RCT (EORTC/LYSA/FIL H10). N=1,950 patients with newly diagnosed localized classical Hodgkin lymphoma, stratified into favorable (H10F, n=754) and unfavorable (H10U, n=1,196) cohorts. After 2 cycles of ABVD, interim PET (iPET) was performed. iPET-negative patients were randomized to standard combined modality therapy (CMT: ABVD + INRT) or response-adapted chemotherapy alone (RT omitted). iPET-positive patients received BEACOPPesc-based intensification plus INRT.
Interventions and follow up
Arm A: ABVD (3–6 cycles total) + involved-node radiotherapy (INRT, 30 Gy) — standard CMT
Arm B: ABVD alone — RT omitted in iPET-negative patients (response-adapted)
Primary endpoint: PFS; noninferiority of RT omission in iPET-negative patients
Median follow-up: 10 years (Federico et al, JCO 2024)
Arm B: ABVD alone — RT omitted in iPET-negative patients (response-adapted)
Primary endpoint: PFS; noninferiority of RT omission in iPET-negative patients
Median follow-up: 10 years (Federico et al, JCO 2024)
Results
H10F — 10-yr PFS (CMT vs chemo alone): 98.8% vs 85.4%, HR 13.2 (95% CI 3.1–55.8), P<.001 — noninferiority not met; arm stopped early
H10U — 10-yr PFS (CMT vs chemo alone): 91.4% vs 86.5%, HR 1.52 (95% CI 0.84–2.75), P for noninferiority=.858 — noninferior
H10F — 10-yr OS: 98.6% (CMT) vs 95.6% (chemo alone)
H10U — 10-yr OS: 95.1% (CMT) vs 93.5% (chemo alone)
H10U — 10-yr PFS (CMT vs chemo alone): 91.4% vs 86.5%, HR 1.52 (95% CI 0.84–2.75), P for noninferiority=.858 — noninferior
H10F — 10-yr OS: 98.6% (CMT) vs 95.6% (chemo alone)
H10U — 10-yr OS: 95.1% (CMT) vs 93.5% (chemo alone)
Adverse events
Early stopping: H10F chemotherapy-alone arm stopped early (IDMC recommendation) due to excess relapses after 5-year interim analysis
Intensification/late effects: BEACOPPesc escalation for iPET-positive patients caused grade ≥3 hematologic toxicity ~50%; long-term RT-related secondary malignancies and cardiovascular events reported at 10 years but not systematically quantified per arm
Intensification/late effects: BEACOPPesc escalation for iPET-positive patients caused grade ≥3 hematologic toxicity ~50%; long-term RT-related secondary malignancies and cardiovascular events reported at 10 years but not systematically quantified per arm
Conclusions
In favorable early-stage cHL (H10F), RT omission in iPET-negative patients resulted in a 13.4 percentage-point deficit in 10-year PFS — the trial arm was stopped early. In unfavorable cHL (H10U), PET-guided RT omission after BEACOPPesc-based intensification met noninferiority criteria at 10 years, supporting a chemotherapy-only approach in this setting when intensive induction is used.
Key Limitations
H10F was terminated early, limiting statistical power for OS analysis. The H10U noninferiority result applies specifically to patients receiving BEACOPPesc — not ABVD-based management — limiting applicability in countries that do not routinely use BEACOPPesc. INRT fields were larger than current ISRT; late-effect estimates may overstate modern RT harm. The iPET threshold (Deauville ≤2) was centrally read, which may not reflect routine practice accuracy. No comparison with more intensive chemotherapy (e.g., 4×ABVD) without RT was conducted.
Clinical Context
H10, together with RAPID, provides the strongest evidence against RT omission in PET-negative early-stage favorable cHL after standard ABVD — incorporated into ESMO 2024 guidelines maintaining CMT as the standard. The H10U finding (RT omission noninferior after BEACOPPesc) aligns with HD17 data and has influenced European guidelines for intensive approaches. Ongoing trials (e.g., GHSG HD16) test PET-adapted strategies in early-stage cHL with 4×ABVD.