What is the recommended approach for managing relapsed Hodgkin's (Hodgkin lymphoma)?

Management of Relapsed Hodgkin Lymphoma

For most patients with relapsed or refractory Hodgkin lymphoma, high-dose chemotherapy followed by autologous stem cell transplantation (ASCT) represents the standard of care and treatment of choice. 1

Initial Assessment and Risk Stratification

When evaluating a patient with relapsed Hodgkin lymphoma, determine the following prognostic factors that will guide treatment intensity:

• Timing of relapse: Early relapse (<12 months from remission) vs. late relapse (>12 months) significantly impacts treatment approach 1
• Disease extent: Stage at relapse (I/II vs. III/IV), presence of B symptoms, and extranodal disease 1, 2
• Prior treatment exposure: Number of previous lines of therapy and whether the patient received prior ASCT 1
• Response to initial therapy: Primary refractory disease carries worse prognosis than relapsed disease 3

Standard Treatment Algorithm for Transplant-Eligible Patients

Step 1: Salvage Chemotherapy (2-3 cycles)

Administer platinum-based salvage chemotherapy to reduce tumor burden and mobilize stem cells before ASCT. 1, 4 The recommended regimens include:

• DHAP (dexamethasone/high-dose cytarabine/cisplatin) 1, 4
• ICE (ifosfamide/carboplatin/etoposide) 1, 4
• IGEV (ifosfamide/gemcitabine/vinorelbine) 1, 4

Critical goal: Achieve PET-negative status after salvage therapy, as this is the most important predictor of post-ASCT outcome. 1, 4 Response to salvage chemotherapy is the strongest prognostic factor for freedom from treatment failure and overall survival. 3

Alternative approach: Single-agent brentuximab vedotin may be sufficient as salvage therapy before ASCT in selected patients. 1 This is FDA-approved for relapsed classical Hodgkin lymphoma after failure of at least two prior multi-agent chemotherapy regimens. 5

Step 2: High-Dose Chemotherapy with ASCT

All patients achieving chemosensitive disease (complete or partial response) after salvage therapy should proceed to high-dose chemotherapy followed by ASCT. 1

• High-risk patients (primary refractory disease, early relapse, multiple relapses) may benefit from tandem ASCT 1
• Consolidation with brentuximab vedotin following ASCT is recommended for patients with defined poor-risk factors 1, 5

Step 3: Radiation Therapy Considerations

• For patients with single PET-positive lymph nodes after salvage therapy: Radiotherapy before ASCT may be discussed 1
• For localized late relapses: Salvage radiotherapy alone may be sufficient in highly selected cases 1

Management After ASCT Failure

First-Line Post-ASCT Options

Single-agent brentuximab vedotin is the preferred option for patients failing ASCT, with an overall response rate of 75% in pivotal studies. 1, 5

Second-Line Post-ASCT Options

Nivolumab or pembrolizumab are FDA-approved for patients with disease recurrence after ASCT and brentuximab vedotin therapy. 1, 6 These checkpoint inhibitors represent standard options in this heavily pretreated population.

Allogeneic Stem Cell Transplantation

Allogeneic SCT represents a potentially curative option for young, chemosensitive patients in good general condition who relapse after ASCT. 1 This should be considered after careful evaluation of the risk-benefit ratio, as it carries significant treatment-related morbidity and mortality. 1 This approach should ideally be conducted within clinical trials. 1

Special Populations and Scenarios

Low-Risk Patients with Late Relapse

Patients relapsing after only two cycles of chemotherapy followed by radiotherapy can be successfully salvaged with more intensive conventional chemotherapy such as BEACOPPescalated, without necessarily requiring ASCT. 1

Non-Transplant Candidates

For patients with multiple relapses who have exhausted transplant options or are not transplant candidates:

• Gemcitabine-based palliative chemotherapy (single agent or in combination) 1
• Regional radiotherapy for localized disease 1
• Brentuximab vedotin is also FDA-approved for patients not candidates for ASCT after at least two prior lines of therapy 1, 5

These approaches can achieve acceptable remission rates, satisfying quality of life, and prolonged survival. 1

Critical Pitfalls to Avoid

• Do not delay ASCT in responding patients: The window of chemosensitivity is critical; patients achieving response to salvage therapy should proceed expeditiously to transplant 1, 4
• Do not use reduced-intensity conditioning allogeneic transplant as standard first-line salvage: This remains investigational and should be reserved for post-ASCT failures 1
• Do not accept PET-positive status before ASCT: Additional salvage cycles or consideration of radiotherapy to PET-positive sites should be pursued, as PET negativity before ASCT is the goal 1, 4
• Do not overlook consolidation brentuximab vedotin post-ASCT: This significantly improves outcomes in high-risk patients and should be routinely considered 1, 5