What is the treatment regimen and recommendation for the HD21 (Hodgkin Disease 21) trial in oncology?

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HD21 Trial: BrECADD vs eBEACOPP in Advanced Hodgkin Lymphoma

The HD21 trial demonstrated that BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone) is superior to eBEACOPP (escalated BEACOPP) for advanced-stage classical Hodgkin lymphoma, with significantly better tolerability and improved progression-free survival. 1

Trial Design and Patient Population

The HD21 trial was a randomized, multicentre, phase 3 trial conducted by the German Hodgkin Study Group that enrolled patients with:

  • Advanced-stage classical Hodgkin lymphoma (Ann Arbor stage III/IV)
  • Stage II with B symptoms and either large mediastinal mass or extranodal lesions
  • Age ≤60 years

Patients were randomized 1:1 to receive either:

  1. BrECADD regimen: Brentuximab vedotin 1.8 mg/kg (day 1), etoposide, cyclophosphamide, doxorubicin, dacarbazine, and dexamethasone
  2. eBEACOPP regimen: Escalated doses of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone

BrECADD Regimen Details

Drug Dose Administration Days
Brentuximab vedotin 1.8 mg/kg IV Day 1
Etoposide 150 mg/m² IV Days 2-4
Cyclophosphamide 1250 mg/m² IV Day 2
Doxorubicin 40 mg/m² IV Day 2
Dacarbazine 250 mg/m² IV Days 3-4
Dexamethasone 40 mg PO Days 2-5

eBEACOPP Regimen Details

Drug Dose Administration Days
Bleomycin 10 mg/m² IV Day 8
Etoposide 200 mg/m² IV Days 1-3
Doxorubicin 35 mg/m² IV Day 1
Cyclophosphamide 1250 mg/m² IV Day 1
Vincristine 1.4 mg/m² (max 2 mg) IV Day 8
Procarbazine 100 mg/m² PO Days 1-7
Prednisone 40 mg/m² PO Days 1-14
G-CSF - SC From day 8

Key Results

The HD21 trial demonstrated several important findings:

  • Treatment-related morbidity: Significantly lower with BrECADD (42%) compared to eBEACOPP (59%) 1
  • Progression-free survival: Superior with BrECADD (94.3% at 4 years) versus eBEACOPP (90.9% at 4 years) 1
  • Overall survival: Similar between groups (98.6% for BrECADD vs 98.2% for eBEACOPP at 4 years) 1

PET-Guided Approach

The HD21 trial incorporated PET assessment after two cycles of therapy to guide treatment decisions:

  • Treatment was guided by PET after two cycles
  • This approach allows for response-adapted therapy, potentially reducing toxicity while maintaining efficacy

Clinical Implications

The HD21 trial results represent a significant advancement in the treatment of advanced Hodgkin lymphoma:

  • BrECADD offers improved tolerability with better efficacy compared to the previous standard eBEACOPP
  • The regimen incorporates targeted therapy (brentuximab vedotin) with conventional chemotherapy
  • The PET-guided approach allows for personalized treatment decisions

Toxicity Profile

BrECADD demonstrated a more favorable toxicity profile compared to eBEACOPP:

  • Lower rates of severe hematologic toxicities
  • Reduced risk of infertility
  • Lower incidence of infections
  • Peripheral neuropathy remains a concern with brentuximab vedotin but is generally manageable

Conclusion

The HD21 trial establishes BrECADD as the new standard of care for advanced-stage classical Hodgkin lymphoma, offering improved tolerability and efficacy compared to eBEACOPP. This regimen represents an important evolution in treatment by incorporating targeted therapy with conventional chemotherapy in a PET-guided approach.

References

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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