What is the recommended treatment regimen for Hodgkin lymphoma based on the HD17 trial summary?

Treatment Regimen for Hodgkin Lymphoma Based on the HD17 Trial

Based on the HD17 trial, PET-guided treatment consisting of 2 cycles of eBEACOPP plus 2 cycles of ABVD chemotherapy (2+2 regimen) followed by omission of radiotherapy in PET-negative patients is the recommended treatment for early-stage unfavorable Hodgkin lymphoma. 1

HD17 Trial Summary and Implications

The HD17 trial was a multicenter, open-label, randomized phase 3 trial conducted by the German Hodgkin Study Group that evaluated whether radiotherapy could be safely omitted in patients who achieved complete metabolic response after chemotherapy. The trial specifically investigated:

• Patient population: Early-stage unfavorable Hodgkin lymphoma patients (ages 18-60)
• Treatment arms:
  • Standard arm: 2 cycles eBEACOPP + 2 cycles ABVD followed by 30 Gy involved-field radiotherapy (IFRT)
  • Experimental arm: 2 cycles eBEACOPP + 2 cycles ABVD followed by radiotherapy only if PET-positive after chemotherapy

Key Results

• At median follow-up of 46.2 months, 5-year progression-free survival was:
  • 97.3% in the standard combined-modality treatment group
  • 95.1% in the PET-guided treatment group
• The between-group difference was only 2.2%, which was below the non-inferiority margin of 8% 1
• PET-negative patients after the 2+2 regimen could safely omit radiotherapy without clinically relevant loss of efficacy

Treatment Algorithm Based on HD17

1. Initial Treatment for Early-Stage Unfavorable Hodgkin Lymphoma:

   • 2 cycles of eBEACOPP + 2 cycles of ABVD (2+2 regimen)

2. Post-Chemotherapy Assessment:

   • Perform PET scan after completion of chemotherapy

3. Treatment Decision Based on PET Results:

   • If PET-negative: No further treatment required
   • If PET-positive: Administer 30 Gy involved-site radiotherapy (ISRT)

Radiation Therapy Considerations from HD17

The HD17 trial also provided important insights regarding radiation therapy approaches:

• ISRT is equally effective and less toxic than IFRT for patients requiring radiation therapy 2
• Acute grade 3/4 toxicities occurred in 8.5% of IFRT patients versus only 2.6% of ISRT patients 2
• Pattern of recurrence analyses showed that none of the disease progressions in the ISRT group would have been prevented by using IFRT 2

Context Within Broader Hodgkin Lymphoma Treatment Guidelines

The HD17 findings represent an evolution from previous treatment standards:

• Earlier guidelines recommended combined modality treatment with 2-3 cycles of ABVD followed by 20-30 Gy ISRT for limited-stage disease 3
• For intermediate stage disease, 4 cycles of ABVD followed by 30 Gy IFRT was previously considered standard 3
• The HD17 trial now provides evidence that PET-guided omission of radiotherapy is safe in early-stage unfavorable disease

Important Considerations and Caveats

• The 2+2 regimen (eBEACOPP+ABVD) used in HD17 differs from the standard ABVD-only approach used in many countries
• eBEACOPP is associated with higher toxicity, including increased rates of infertility, myelosuppression, and infections 4
• BEACOPP-based regimens should be avoided in patients >60 years due to increased treatment-related mortality 4
• Long-term follow-up is essential due to potential late effects of treatment, including second malignancies and cardiac toxicity 4

Practical Implementation

For patients with early-stage unfavorable Hodgkin lymphoma:

1. Confirm diagnosis and staging with appropriate workup
2. Administer 2 cycles of eBEACOPP followed by 2 cycles of ABVD
3. Perform PET scan after completion of chemotherapy
4. If PET-negative: No further treatment required
5. If PET-positive: Administer 30 Gy ISRT
6. Implement appropriate follow-up schedule to monitor for relapse and late effects

This PET-guided approach allows for reduction in the proportion of patients exposed to the potential late effects of radiotherapy while maintaining excellent disease control.