What is the treatment for first relapse of Classical Hodgkin's Lymphoma (CHL)?

From the Guidelines

For patients with first relapse of classic Hodgkin's lymphoma, the recommended treatment approach involves salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT). The most recent and highest quality study 1 supports this approach, which provides intensive therapy to overcome chemoresistance while the autologous transplant allows for dose intensification with stem cell rescue to restore bone marrow function.

Key Considerations

• Common salvage chemotherapy regimens include ICE (ifosfamide 5000 mg/m² divided over 2 days, carboplatin AUC=5, etoposide 100 mg/m² daily for 3 days), DHAP (dexamethasone 40 mg daily for 4 days, high-dose cytarabine 2000 mg/m² twice on day 2, cisplatin 100 mg/m² on day 1), or GDP (gemcitabine 1000 mg/m² days 1 and 8, dexamethasone 40 mg days 1-4, cisplatin 75 mg/m² day 1) 1.
• Typically, 2-3 cycles of salvage chemotherapy are given before proceeding to stem cell collection and ASCT.
• For patients who achieve a complete or partial response to salvage therapy, the BEAM conditioning regimen (BCNU 300 mg/m², etoposide 800 mg/m², cytarabine 1600 mg/m², melphalan 140 mg/m²) is commonly used before ASCT.
• For patients with refractory disease or high-risk features, brentuximab vedotin (1.8 mg/kg every 3 weeks) or PD-1 inhibitors like pembrolizumab (200 mg every 3 weeks) or nivolumab (240 mg every 2 weeks) may be incorporated into the treatment plan.

Prognostic Factors and Treatment Stratification

• Three major prognostic factors at relapse (refractoriness, short disease-free interval, and disseminated disease) allow stratification of patients into three meaningful risk groups 1.
• Patients with high-risk disease should be oriented to tandem transplantation provided that they display chemosensitivity and no progression between the two transplants.
• Patients with intermediate-risk disease or standard-risk with any additional risk factors can be treated with single transplantation.
• In some selected standard-risk patients with chemosensitivity and no additional risk factors, a strategy without HDT could be applied.

Monitoring and Response Evaluation

• Screening for response to salvage treatment is central to this program and should be performed with CT scanning and FDG-PET interpreted with criteria adapted for interim response analysis 1.
• Based on PET-guided evaluation, every effort should be made to increase the proportion of chemosensitive patients, by alternating non-cross-resistant chemotherapy lines or exploring the role of novel drugs.

From the Research

Treatment Options for Classic Hodgkin's Lymphoma First Relapse

• The treatment for classic Hodgkin's lymphoma first relapse involves salvage chemotherapy regimens, which may include ifosfamide, carboplatin, and etoposide (ICE) or other combinations such as etoposide, steroid, and cytarabine cisplatin (ESHAP) 2.
• Studies have compared the efficacy of different salvage chemotherapy regimens, including ICE and ESHAP, with ESHAP showing higher response rates in some cases 2.
• The addition of checkpoint inhibitors, such as pembrolizumab or nivolumab, to conventional chemotherapy regimens like ICE has shown promising results in terms of complete response rates and overall survival 3, 4.
• High-dose chemotherapy with autologous stem cell transplantation is also considered a treatment option for relapsed or refractory Hodgkin's lymphoma, with salvage regimens like ICE or IVAD (ifosfamide, etoposide, cytarabine, and dexamethasone) used to achieve complete remission before transplantation 5, 6.

Efficacy of Different Salvage Chemotherapy Regimens

• A study comparing ICE and ESHAP regimens found that ESHAP had higher response rates, with 39.7% of patients achieving complete remission and 19.2% achieving partial remission, compared to 21.9% and 17.1% for ICE, respectively 2.
• Another study found that the ICE regimen had higher response rates compared to the DHAP (cytosine arabinoside, cisplatin, and dexamethasone) regimen, with 27% of patients achieving complete remission and 41% achieving partial remission, compared to 18% and 30% for DHAP, respectively 6.
• The addition of pembrolizumab to ICE chemotherapy resulted in a complete response rate of 86.5% and an overall response rate of 97.3% in patients with relapsed or refractory classic Hodgkin lymphoma 3.
• Nivolumab plus ICE chemotherapy was also found to be highly effective, with a complete response rate of 86% and an overall response rate of 100% in patients with high-risk relapsed or refractory Hodgkin lymphoma 4.

Safety and Toxicity of Salvage Chemotherapy Regimens

• The toxicity profiles of different salvage chemotherapy regimens, including ICE and ESHAP, have been found to be within acceptable limits, with hematological toxicities such as neutropenia and thrombocytopenia being the most common 2, 6.
• The addition of checkpoint inhibitors like pembrolizumab or nivolumab to conventional chemotherapy regimens has been found to be well-tolerated, with immune-related toxicities being generally manageable 3, 4.