Relapsed and refractory classical Hodgkin lymphoma: the decisions you may face
5 treatment settings, 5 with more than one named option. Each section lays out the options the standard of care names, what each is for, the trials behind them with their recorded results, the side effects and cautions on record, and questions to ask. Built from the cancer page's standard-of-care rows; nothing here is advice for your case.
Salvage before transplant
Platinum-based chemotherapy (ICE, DHAP, GVD) increasingly combined with brentuximab vedotin or pembrolizumab, or brentuximab vedotin with nivolumab, to reach PET-negative remission.
The ADC that made the modern field credible (2011), for Hodgkin lymphoma and CD30+ lymphomas.
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
A versatile chemotherapy used in pancreatic, bladder, lung, ovarian, breast and biliary cancers, in nasopharyngeal cancer, and as a bladder instillation.
FDG PET is the standard PET scan. A radioactive sugar shows which tissues are burning glucose fast, which most cancers do.
- Universal availability
- Decades of validation
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Neutropenia · ECHELON-1, A+AVD arm | 91% | 82% |
| Febrile neutropenia · ECHELON-1, A+AVD arm | 19% | 19% |
| Peripheral sensory neuropathy · ECHELON-1, A+AVD arm | 65% | 10% |
| Vomiting · ECHELON-1, A+AVD arm | 33% | 3% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Non-specific: infection and inflammation are also hot
- Brain background
- Poor in indolent tumours
- Between Brentuximab vedotin, Nivolumab, Pembrolizumab and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- Which side effects of Brentuximab vedotin or Nivolumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Hodgkin Lymphoma), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (salvage before transplant), which of the standard options do you recommend and why?Why: Guideline options include: Platinum-based chemotherapy (ICE, DHAP, GVD) increasingly combined with brentuximab vedotin or pembrolizumab, or brentuximab vedotin with nivolumab, to reach PET-negative remission.
- Am I a candidate for Brentuximab vedotin, Nivolumab, Pembrolizumab or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.
Consolidation
High-dose chemotherapy with autologous stem cell transplantation for chemosensitive relapse; brentuximab vedotin maintenance for a year in high-risk patients (AETHERA).
Autologous stem cell transplant collects the patient's own blood-forming stem cells, gives melphalan or another chemotherapy at a dose that would otherwise destroy the marrow, then returns the cells to rebuild it. It is standard consolidation in myeloma and for relapsed lymphoma, though CAR-T has displaced it in early-relapsing large B-cell lymphoma.
- Permits dose intensity impossible otherwise
- Decades of outcome data
- Widely available
The ADC that made the modern field credible (2011), for Hodgkin lymphoma and CD30+ lymphomas.
- High-risk Hodgkin lymphoma after autologous transplant: brentuximab vedotin consolidation vs placebo
PFS HR 0.57.
Progression-free survival (median) (months): Brentuximab vedotin 42.9 (n=165) vs Placebo 24.1 (n=164) · HR 0.57 · source
- Treatment-related mortality ~1-2% (myeloma) to higher in children
- Infertility, second malignancies, prolonged cytopenias
- Being challenged by CAR-T and MRD-guided deferral
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Neutropenia · ECHELON-1, A+AVD arm | 91% | 82% |
| Febrile neutropenia · ECHELON-1, A+AVD arm | 19% | 19% |
| Peripheral sensory neuropathy · ECHELON-1, A+AVD arm | 65% | 10% |
| Vomiting · ECHELON-1, A+AVD arm | 33% | 3% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Between Autologous stem cell transplant (high-dose therapy) and Brentuximab vedotin, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in AETHERA, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Brentuximab vedotin are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Hodgkin Lymphoma), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (consolidation), which of the standard options do you recommend and why?Why: Guideline options include: High-dose chemotherapy with autologous stem cell transplantation for chemosensitive relapse; brentuximab vedotin maintenance for a year in high-risk patients (AETHERA).
- Am I a candidate for Brentuximab vedotin, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of AETHERA apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Relapse after transplant
Pembrolizumab (KEYNOTE-204) or nivolumab (CheckMate 205); brentuximab vedotin if not previously given; PD-1 antibodies in China include penpulimab and others.
Pembrolizumab is a PD-1 blocking antibody approved in more than 40 settings, from melanoma and lung cancer to the first tumour-agnostic approval for mismatch-repair-deficient tumours in 2017, and before and after surgery in triple-negative breast cancer. A subcutaneous form arrived in 2025, and it is the backbone partner for ADCs and personalised neoantigen vaccines.
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
The ADC that made the modern field credible (2011), for Hodgkin lymphoma and CD30+ lymphomas.
Penpulimab is a Chinese PD-1 antibody approved in the US in 2025 for nasopharyngeal carcinoma, the second after toripalimab.
Immune checkpoint inhibitors are antibodies against CTLA-4, PD-1 or PD-L1 that release the brakes on T cells so they attack the cancer. They are approved in more than 20 tumour types and produce lasting, sometimes curative responses that chemotherapy rarely does, but most patients do not respond and autoimmune side effects are the cost.
- Durable, sometimes curative responses
- Broad applicability
- Tests Pembrolizumab, Brentuximab vedotinRelapsed/refractory classical Hodgkin lymphoma: pembrolizumab vs brentuximab vedotin
PFS 13.2 vs 8.3 months, HR 0.65.
Progression-free survival (median) (months): Pembrolizumab 13.2 (n=151) vs Brentuximab vedotin 8.3 (n=153) · HR 0.65 · source - Tests NivolumabRelapsed/refractory classical Hodgkin lymphoma after autologous transplant: nivolumab (cohorts A-C); cohort D nivolumab-AVD frontline
ORR 69%.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Hypothyroidism (immune-mediated) · Pooled monotherapy data, >2,800 patients | 8% | - |
| Pneumonitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 3.4% | - |
| Colitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 1.7% | - |
| Hepatitis (immune-mediated) · Pooled monotherapy data, >2,800 patients | 0.7% | - |
- No pharmacokinetic interactions expected (antibody). See the irAE guide for toxicity management.
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Neutropenia · ECHELON-1, A+AVD arm | 91% | 82% |
| Febrile neutropenia · ECHELON-1, A+AVD arm | 19% | 19% |
| Peripheral sensory neuropathy · ECHELON-1, A+AVD arm | 65% | 10% |
| Vomiting · ECHELON-1, A+AVD arm | 33% | 3% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Most patients do not respond
- Autoimmune toxicity
- Biomarkers are imperfect
- Between Pembrolizumab, Nivolumab, Brentuximab vedotin and the other options, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in KEYNOTE-204 and CheckMate 205, and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- Which side effects of Pembrolizumab or Nivolumab are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Hodgkin Lymphoma), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (relapse after transplant), which of the standard options do you recommend and why?Why: Guideline options include: Pembrolizumab (KEYNOTE-204) or nivolumab (CheckMate 205); brentuximab vedotin if not previously given; PD-1 antibodies in China include penpulimab and others.
- Am I a candidate for Pembrolizumab, Nivolumab, Brentuximab vedotin or related drugs, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of KEYNOTE-204 and CheckMate 205 apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Failure of PD-1 antibodies and brentuximab
Allogeneic transplantation for fit patients; bendamustine, gemcitabine or everolimus; CD30 CAR T cells and bispecific antibodies in trials.
Allogeneic stem cell transplantation replaces a patient's blood system with a donor's after conditioning chemotherapy, so donor immune cells hunt down leukaemia left behind. It remains the only cure for adverse-risk acute myeloid leukaemia, high-risk acute lymphoblastic leukaemia and Richter transformation, at the price of graft-versus-host disease.
- Curative for otherwise incurable leukaemia
- Graft-versus-leukaemia is an antigen-agnostic immune therapy
A versatile chemotherapy used in pancreatic, bladder, lung, ovarian, breast and biliary cancers, in nasopharyngeal cancer, and as a bladder instillation.
An mTOR-blocking pill that doubled progression-free time with exemestane in 2012 and is now paired with the oral SERD giredestrant.
- Phase 2 Study Evaluating Autologous CD30.CAR-T Cells in Patients With Relapsed/Refractory Hodgkin Lymphoma (CHARIOT)Phase 2NCT0426870697 peopleevidence 30A Phase 2 Multi-Center Study Evaluating the Safety and Efficacy of CD30-Directed Genetically Modified Autologous T Cells (CD30.CAR-T) in Adult and Pediatric Patients With Relapsed or Refractory Classical Hodgkin Lymphoma
No headline result recorded yet.
- Treatment-related mortality 10-20%
- Chronic GVHD
- Relapse remains the main cause of failure
- Avoid grapefruit. Live vaccines are contraindicated.
- 7.5 mg (mild), 5 mg (moderate), 2.5 mg (severe).
- Between Allogeneic stem cell transplantation, Gemcitabine and Everolimus, which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- How closely do I match the people in Phase 2 Study Evaluating Autologous CD30.CAR-T Cells in Patients With Relapsed/Refractory Hodgkin Lymphoma (CHARIOT), and does that change what the results mean for me?Why: Trial populations are selected; age, fitness, prior treatment and biomarkers all affect how far results carry.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Hodgkin Lymphoma), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (failure of pd-1 antibodies and brentuximab), which of the standard options do you recommend and why?Why: Guideline options include: Allogeneic transplantation for fit patients; bendamustine, gemcitabine or everolimus; CD30 CAR T cells and bispecific antibodies in trials.
- Am I a candidate for Gemcitabine, Everolimus, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
- How do the results of Phase 2 Study Evaluating Autologous CD30.CAR-T Cells in Patients With Relapsed/Refractory Hodgkin Lymphoma (CHARIOT) apply to someone like me?Why: Trial populations differ from individual patients; ask how closely you match.
Add these to your appointment list, or take the full question set for this cancer.
Transplant-ineligible patients
PD-1 antibody with or without brentuximab vedotin as ongoing therapy; palliative radiotherapy for symptomatic sites.
Nivolumab was the second PD-1 blocker and is often combined with ipilimumab. Long-term data show about half of advanced melanoma patients alive at 10 years on the combination.
The ADC that made the modern field credible (2011), for Hodgkin lymphoma and CD30+ lymphomas.
IMRT and IGRT shape the radiation beam to the tumour's outline from multiple angles and check the patient's position with a scan before every session, so surrounding organs receive less dose. Fewer, larger doses are now standard in breast and prostate cancer, but a low-dose bath still spreads across normal tissue.
- Conformal dose, fewer side effects
- Hypofractionation saves visits
No trial record is attached to this row yet. The trials tab lists what is recruiting and the landmark trials for this cancer.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Colitis with ipilimumab (1+3 mg/kg) · Monotherapy pooled unless stated | 25% | 14.4% |
| Hepatitis with ipilimumab · Monotherapy pooled unless stated | 15% | 13.4% |
| Colitis · Monotherapy pooled unless stated | 2.9% | 1.7% |
| Hepatitis · Monotherapy pooled unless stated | 1.8% | 1.5% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
| Side effect | Any grade | Grade 3+ |
|---|---|---|
| Neutropenia · ECHELON-1, A+AVD arm | 91% | 82% |
| Febrile neutropenia · ECHELON-1, A+AVD arm | 19% | 19% |
| Peripheral sensory neuropathy · ECHELON-1, A+AVD arm | 65% | 10% |
| Vomiting · ECHELON-1, A+AVD arm | 33% | 3% |
Rates from the label or pivotal trial as recorded on the product page; each grade 3+ figure links to its source.
- Low-dose bath to normal tissue
- Motion management
- Between Nivolumab, Brentuximab vedotin and IMRT / IGRT (modern external beam), which do you recommend for me, and what about my case would make you choose differently?Why: Guidelines list several reasonable options; the choice turns on details of your tumour, your health and your priorities.
- What is each option trying to achieve: cure, long control, or relief of symptoms, and over what time?Why: The aim shapes how much side effect and disruption is worth accepting.
- Which side effects of Nivolumab or Brentuximab vedotin are most likely for me, which are reversible, and which would make us stop?Why: The recorded rates below come from labels and trials; your own risk depends on dose, other medicines and your health.
- What happens if I delay, or decline this step for now? Is the decision reversible?Why: Some decisions can wait for a second opinion or a trial slot; others cannot. Knowing which is part of the choice.
- Does your recommendation follow the current guideline (NCCN Guidelines: Hodgkin Lymphoma), and if it departs from it, why?Why: Departures from guidelines are sometimes right for an individual; they should be explained.
- For my situation (transplant-ineligible patients), which of the standard options do you recommend and why?Why: Guideline options include: PD-1 antibody with or without brentuximab vedotin as ongoing therapy; palliative radiotherapy for symptomatic sites.
- Am I a candidate for Nivolumab, Brentuximab vedotin, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Add these to your appointment list, or take the full question set for this cancer.