What are the most notable clinical trials in Hodgkin lymphoma?

Famous Clinical Trials in Hodgkin Lymphoma

The most notable clinical trials in Hodgkin lymphoma include the German Hodgkin Study Group (GHSG) HD7, HD8, HD10, and HD11 trials, along with the European Organisation for Research and Treatment of Cancer (EORTC) H7, H8, and subsequent trials, which have revolutionized treatment approaches and significantly improved survival outcomes. 1, 2

Early Stage Disease Trials

GHSG Trials

• HD7 Trial: Compared extended-field radiotherapy (EF-RT) alone versus combined modality therapy (CMT) with 2 cycles of ABVD followed by EF-RT in early-stage favorable HL. Results showed 15-year progression-free survival (PFS) of 73% for CMT versus 52% for RT alone, definitively establishing the superiority of combined modality treatment. 2

• HD10 Trial: Demonstrated that 2 cycles of ABVD plus 20 Gy involved-field RT (IF-RT) was non-inferior to 4 cycles of ABVD plus 30 Gy IF-RT in early favorable HL, with 10-year PFS of 87% in both arms. This landmark study established the current standard of care for early favorable disease. 2

• HD8 Trial: Showed that involved-field RT was non-inferior to extended-field RT after chemotherapy in unfavorable early-stage disease, allowing for reduction in radiation fields and associated toxicity. 1, 2

• HD11 Trial: Compared ABVD versus baseline BEACOPP followed by either 20 Gy or 30 Gy IF-RT in early unfavorable HL. Found that after BEACOPP, 20 Gy was non-inferior to 30 Gy, but with ABVD, 30 Gy provided better disease control than 20 Gy. 2

EORTC Trials

• H7 Trial: Compared subtotal nodal irradiation (STNI) versus 6 cycles of EBVP followed by IF-RT in favorable patients, establishing that combined modality treatment could replace STNI. 1

• H8 Trial:

  • H8-F (favorable): Compared STNI alone versus 3 cycles of MOPP-ABV plus IF-RT, showing superiority of combined modality treatment. 1
  • H8-U (unfavorable): Compared 6 cycles of MOPP-ABV+IF-RT versus 4 cycles of MOPP-ABV+STNI versus 4 cycles of MOPP-ABV+IF-RT, demonstrating that 4 cycles were sufficient. 1

Advanced Stage Disease Trials

GHSG Trials

• HD9 Trial: Established the superiority of escalated BEACOPP over standard BEACOPP and COPP/ABVD in advanced HL, with significantly improved freedom from treatment failure and overall survival. 3

EORTC Trials

• H34 Trial: Compared MOPP/ABV hybrid versus alternating MOPP and ABVD in advanced disease. 4

PET-Guided Treatment Trials

• RAPID Trial and H10 Trial: Investigated whether radiation therapy could be omitted in patients with negative interim PET after chemotherapy. Both showed PFS advantage for combined modality approaches despite negative interim PET, though overall survival remained excellent in both arms. 1

Key Findings from These Trials

1. Combined modality treatment is superior to radiation therapy alone in early-stage disease 1

2. De-escalation of therapy is possible in favorable subgroups:

   • Reduction from 4 to 2 cycles of ABVD in favorable early-stage disease 1, 2
   • Reduction of radiation dose from 30 Gy to 20 Gy in selected patients 1
   • Transition from extended-field to involved-field to involved-site RT 1

3. Intensification of therapy with BEACOPP regimens improves disease control in advanced stages but with increased toxicity 1, 3

4. Risk stratification using clinical factors allows for tailored treatment approaches 1

Impact on Current Practice

These landmark trials have established the current standard approaches:

• Early favorable HL: 2 cycles of ABVD + 20 Gy ISRT 1, 5
• Early unfavorable HL: 4 cycles of ABVD + 30 Gy ISRT 1
• Advanced HL: 6-8 cycles of ABVD or escalated BEACOPP based on risk factors 1, 5

Common Pitfalls and Caveats

• Radiation alone is no longer recommended for any stage of Hodgkin lymphoma 1
• PET-guided approaches are promising but have not yet definitively identified patients who can safely omit radiation therapy 1
• Treatment toxicity remains a concern, particularly with more intensive regimens like BEACOPP, which causes higher rates of infertility, myelosuppression, and infections 5
• Age considerations are critical - BEACOPP should be avoided in patients >60 years due to increased treatment-related mortality 5

These trials have collectively transformed Hodgkin lymphoma from a disease with modest cure rates to one with excellent long-term outcomes, with current 5-year survival rates exceeding 90% for early-stage disease 6.