HD16
HD16 for Early Stages - Treatment Optimization Trial in the First-line Treatment of Early Stage Hodgkin Lymphoma; Treatment Stratification by Means of FDG-PET
Phase 3N = 1,150NCT00736320
- Population
- Newly diagnosed early-stage favourable Hodgkin lymphoma (GHSG definition), age 18 to 75 years.
- Design
- International randomised phase III trial, recruitment November 2009 to December 2015. Standard combined-modality treatment (CMT): two cycles of ABVD and 20 Gy involved-field radiotherapy, versus PET-guided treatment: two cycles of ABVD then PET (PET-2), omitting radiotherapy after a negative PET-2 (Deauville score below 3). Primary objectives: to exclude inferiority of 10% or more in 5-year PFS of ABVD alone compared with CMT in a per-protocol analysis among PET-2-negative patients (noninferiority margin for the hazard ratio 3.01), and to confirm PET-2 positivity as a risk factor for PFS among CMT-treated patients.
- Primary endpoint
- PFS
- Arms
- Combined-modality treatment (control): Two cycles of ABVD followed by 20 Gy involved-field radiotherapy
- PET-2-guided treatment (experimental): Two cycles of ABVD, then PET-2; radiotherapy omitted if PET-2 negative (Deauville score below 3), radiotherapy given if positive (ABVD alone in PET-2-negative patients)
- People
- Fuchs M, senior author Engert A, German Hodgkin Study Group
PFSHR 1.78 (95% CI 1.02–3.12)Δ 60-month PFS−7.3 pointsΔ 60-month OS+0.3 pointsPFSHR 2.05 (95% CI 1.20–3.51)Δ 60-month PFS−7.5 pointsΔ 60-month OS+0.5 points
Show the numbers
| Endpoint | Analysis | PET-2-guided treatment | Combined-modality treatment | Effect |
|---|---|---|---|---|
| PFSPET-2-negative, per-protocol-treated patients (628) | primarymedian follow-up 45 monthsFuchs 2019 | 86.1% at 5 y (81.4–90.9%) | 93.4% at 5 y (90.4–96.5%) | HR 1.78 (95% CI 1.02–3.12)628 PET-2-negative, per-protocol-treated patients were analysed. Difference 7.3% (95% CI 1.6% to 13.0%). The hazard ratio is for ABVD alone relative to CMT: the prespecified non-inferiority test concerned ABVD alone over CMT, with a margin of 3.01 for the hazard ratio (stated in the 2019 abstract's methods and in the Methods of the open-access 2024 follow-up). Authors conclude radiotherapy cannot be omitted from CMT in PET-2-negative patients without clinically relevant loss of tumour control. |
| OSPET-2-negative, per-protocol-treated patients (628) | primarymedian follow-up 45 monthsFuchs 2019 | 98.4% at 5 y (96.5–100.0%) | 98.1% at 5 y (96.5–99.8%) | — |
| PFSPET-2-negative, per-protocol-treated patients (CMT n=328; ABVD alone n=300) | long term-updatemedian follow-up 64 monthsFuchs 2024 | 86.7% at 5 y (82.5–90.9%) | 94.2% at 5 y (91.6–96.9%) | HR 2.05 (95% CI 1.20–3.51)P=0.0072Per-protocol population (confirmed in the open full text). Hazard ratio is for ABVD alone relative to CMT; its 95% CI (1.20 to 3.51) includes the prespecified non-inferiority margin of 3.01. The intention-to-treat analysis gave 94.0% vs 86.6%, HR 1.99 (1.19-3.34) (full text, not recorded as a separate Result). The authors conclude that CMT should be considered standard treatment for early-stage favourable Hodgkin lymphoma irrespective of the PET-2 result. |
| OSPET-2-negative, per-protocol-treated patients (CMT n=328; ABVD alone n=300) | long term-updatemedian follow-up 66 monthsFuchs 2024 | 98.8% at 5 y (97.4–100.0%) | 98.3% at 5 y (96.9–99.8%) | P=0.14Per-protocol population. Median follow-up for overall survival is 66 months in the full text (the abstract gives 64 months for the progression-free survival analysis). Of 12 documented deaths (9 after CMT, 3 after ABVD alone), 4 were caused by second primary malignancies and one by Hodgkin lymphoma. |
| Endpoint | Analysis | PET-2-guided treatment | Combined-modality treatment | Effect |
|---|---|---|---|---|
| PFSPET-2-negative, per-protocol-treated patients (628) | primarymedian follow-up 45 monthsFuchs 2019 | 86.1% at 5 y (81.4–90.9%) | 93.4% at 5 y (90.4–96.5%) | HR 1.78 (95% CI 1.02–3.12)628 PET-2-negative, per-protocol-treated patients were analysed. Difference 7.3% (95% CI 1.6% to 13.0%). The hazard ratio is for ABVD alone relative to CMT: the prespecified non-inferiority test concerned ABVD alone over CMT, with a margin of 3.01 for the hazard ratio (stated in the 2019 abstract's methods and in the Methods of the open-access 2024 follow-up). Authors conclude radiotherapy cannot be omitted from CMT in PET-2-negative patients without clinically relevant loss of tumour control. |
| OSPET-2-negative, per-protocol-treated patients (628) | primarymedian follow-up 45 monthsFuchs 2019 | 98.4% at 5 y (96.5–100.0%) | 98.1% at 5 y (96.5–99.8%) | — |
| PFSPET-2-negative, per-protocol-treated patients (CMT n=328; ABVD alone n=300) | long term-updatemedian follow-up 64 monthsFuchs 2024 | 86.7% at 5 y (82.5–90.9%) | 94.2% at 5 y (91.6–96.9%) | HR 2.05 (95% CI 1.20–3.51)P=0.0072Per-protocol population (confirmed in the open full text). Hazard ratio is for ABVD alone relative to CMT; its 95% CI (1.20 to 3.51) includes the prespecified non-inferiority margin of 3.01. The intention-to-treat analysis gave 94.0% vs 86.6%, HR 1.99 (1.19-3.34) (full text, not recorded as a separate Result). The authors conclude that CMT should be considered standard treatment for early-stage favourable Hodgkin lymphoma irrespective of the PET-2 result. |
| OSPET-2-negative, per-protocol-treated patients (CMT n=328; ABVD alone n=300) | long term-updatemedian follow-up 66 monthsFuchs 2024 | 98.8% at 5 y (97.4–100.0%) | 98.3% at 5 y (96.9–99.8%) | P=0.14Per-protocol population. Median follow-up for overall survival is 66 months in the full text (the abstract gives 64 months for the progression-free survival analysis). Of 12 documented deaths (9 after CMT, 3 after ABVD alone), 4 were caused by second primary malignancies and one by Hodgkin lymphoma. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| PFS | 1.78 | 1.02–3.12 |
| PFS | 2.05 | 1.2–3.51 |
Appears in
Sources
Fuchs M, Goergen H, Kobe C, Kuhnert G, Lohri A, Greil R, et al. Positron Emission Tomography-Guided Treatment in Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase III HD16 Trial by the German Hodgkin Study Group. J Clin Oncol. 2019;37(31):2835-2845.
Fuchs M, Jacob AS, Kaul H, Kobe C, Kuhnert G, Pabst T, et al. Follow-up of the GHSG HD16 trial of PET-guided treatment in early-stage favorable Hodgkin lymphoma. Leukemia. 2024;38(1):160-167.