Treatment for Progressive Hodgkin Lymphoma After ABVD and ICE Failure
This patient requires immediate consideration for brentuximab vedotin-based salvage therapy or checkpoint inhibitor therapy (nivolumab/pembrolizumab), with the goal of achieving PET-negativity before proceeding to high-dose chemotherapy and autologous stem cell transplantation (ASCT). 1
Primary Salvage Strategy: Brentuximab Vedotin
Brentuximab vedotin should be the preferred next-line agent for this patient who has progressed through ICE. 2, 3 The evidence strongly supports this approach:
Single-agent brentuximab vedotin can achieve complete metabolic response rates of approximately 27-34% in relapsed/refractory patients, and ESMO guidelines explicitly state that single-agent brentuximab vedotin may be sufficient as salvage therapy before HDCT and ASCT in selected patients. 1, 4
The FDA-approved dosing for relapsed classical Hodgkin lymphoma is 1.8 mg/kg (maximum 180 mg) every 3 weeks until disease progression or unacceptable toxicity. 3
A sequential approach using brentuximab vedotin followed by augmented ICE (if PET remains positive) achieved a 76% complete response rate in a phase 2 study, demonstrating that brentuximab vedotin can salvage patients who failed standard ICE. 1, 4
Alternative Option: Checkpoint Inhibitors
If brentuximab vedotin is contraindicated or unavailable, checkpoint inhibitors (nivolumab or pembrolizumab) represent a valid alternative. 5, 6
Nivolumab is FDA-approved for Hodgkin lymphoma that has relapsed or progressed after ASCT and post-transplantation brentuximab vedotin. 1
These agents have demonstrated high activity in heavily pretreated patients and can be considered in this setting. 6, 7
Critical Goal: Achieving PET-Negativity
The overarching objective of any salvage therapy must be achieving PET-negativity (Deauville score ≤3) before proceeding to ASCT, as this is the strongest predictor of post-transplant outcomes. 1, 2
ESMO guidelines explicitly state that achieving a negative PET should be the goal of salvage therapy, irrespective of the applied protocol. 1
Patients who achieve complete metabolic response before HDCT and ASCT have significantly improved clinical outcomes compared to those with persistent PET-positive disease. 1, 4
Subsequent Management Algorithm
If PET-Negative After Salvage:
Proceed immediately to high-dose chemotherapy followed by ASCT, as this remains the treatment of choice for relapsed/refractory Hodgkin lymphoma. 1, 5
Post-ASCT consolidation with brentuximab vedotin is mandatory for this patient, given the presence of multiple high-risk features (primary disease progression within 5 months after ABVD, which qualifies as early relapse <12 months). 1, 5
The AETHERA trial demonstrated improved progression-free survival with brentuximab vedotin consolidation (up to 16 cycles every 3 weeks) in patients with risk factors including early relapse. 1, 3
If PET-Positive After Salvage:
Consider alternative salvage regimens such as DHAP or IGEV if not previously used. 1
Allogeneic stem cell transplantation may be considered in selected younger patients with continued refractory disease. 5
Important Caveats
This patient's disease is highly aggressive, having relapsed within 5 months of completing ABVD and now progressing through 3 cycles of ICE. 5
This qualifies as primary refractory disease (progression within 3 months of treatment completion or during treatment), which carries the worst prognosis among all relapsed/refractory Hodgkin lymphoma patients. 5
Histological confirmation is recommended before proceeding with salvage therapy to rule out transformation or misdiagnosis, particularly when progression occurs rapidly or in new sites. 5
The likelihood of cure with ASCT alone in this setting is approximately 50%, underscoring the importance of achieving optimal disease control pre-transplant and utilizing post-transplant consolidation. 1, 5