What are the key considerations when delivering 1L treatment for advanced-stage cHL and how can AEs be managed?

The Lymphoma Hub was pleased to speak to Graham Collins, Oxford University Hospitals, UK. We asked, What are the key considerations when delivering 1L treatment for advanced-stage cHL and how can AEs be managed?

In this interview, Collins discusses the considerations guiding first-line (1L) treatment selection in advanced-stage (AS) classical Hodgkin lymphoma (cHL). He explores the evolving treatment landscape, highlighting the importance of balancing treatment efficacy and toxicity, fertility considerations, and patients’ individual priorities.  

Key points 

• 1L treatment options for patients with AS cHL include: 
  • Standard chemotherapy regimens, such as doxorubicin + bleomycin + vinblastine + dacarbazine (ABVD), escalated bleomycin + etoposide + doxorubicin + cyclophosphamide + vincristine + procarbazine + prednisone (eBEACOPP), or eBEACOPP with dacarbazine replacing procarbazine (eBEACOPDac).¹ 
  • Targeted therapy combined with chemotherapy, such as brentuximab vedotin + AVD (BV-AVD), nivolumab + AVD (N-AVD), or brentuximab vedotin + etoposide + cyclophosphamide + doxorubicin + dacarbazine + dexamethasone (BrECADD).¹ 
• Treatment selection is informed by disease characteristics, patient factors and preferences, and local treatment availability.¹ 
• eBEACOPP/eBEACOPDac regimens have demonstrated improved disease control compared with ABVD, for example, in the HD18 trial (NCT00515554), 5-year progression-free survival (PFS) rates were ~90% in patients with cHL who received eBEACOPP compared with ~75% with ABVD in the LYSA H34 trial; however, hospitalization and adverse event (AE) rates can be higher with the more intensive BEACOPP regimen compared with ABVD, highlighting the need to balance efficacy and toxicity.^2–4 
• Results from the phase III ECHELON-1 trial (NCT01712490) showed that BV-AVD increased 6-year PFS rates compared with ABVD (82.3% vs 74.5%; hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.53–0.86); however, febrile neutropenia and peripheral neuropathy require monitoring and management.^5,6 
  • Primary prophylaxis with granulocyte-colony stimulating factor (G-CSF) can reduce the rate and severity of febrile neutropenia in patients with cHL treated with BV-AVD.⁷ 
  • For patients with Grade 2 peripheral neuropathy, dose reductions of brentuximab vedotin and/or vinblastine should be considered. For Grade 3 peripheral neuropathy, treatment interruption or discontinuation of at least one of the neurotoxic agents may be necessary.⁸   
• Results from the phase III SWOG S1826 trial (NCT03907488) showed that N-AVD improves 2-year PFS rates vs BV-AVD (92% vs 83%; HR, 0.45; 95% CI, 0.3–0.65), with better tolerability, suggesting that N-AVD is an effective regimen for this patient population, particularly for older patients.⁹ 
  • Checkpoint inhibitors, such as nivolumab, can cause immune-related AEs, highlighting the importance of regular monitoring, prompt recognition of symptoms, and management according to institutional protocols.¹⁰ 
• Results from the phase III HD21 trial (NCT02661503) showed that BrECADD is associated with a 4-year PFS rate of 94.3% vs 90.9% with eBEACOPP (HR, 0.66; 95% CI, 0.45–0.97), with significantly lower treatment-related morbidity with BrECADD (42% vs 59%; relative risk, 0.72; 95% CI, 0.65–0.80; p < 0.0001).¹¹ 
• Patients should be evaluated for and counseled about reproductive risk and fertility preservation, including sperm cryopreservation for male patients, and oocyte or embryo cryopreservation for female patients.¹² 
• Collins concludes by highlighting the importance of considering the patients’ individual circumstances and preferences, including treatment burden, hospitalization risk, and family planning.¹³

This educational resource is independently supported by Takeda Pharmaceuticals U.S.A., Inc. All content is developed by SES in collaboration with an expert steering committee. Funders are allowed no influence.