Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

early (stage I to II) classical HL: favourable disease and intended for combined-modality therapy

1st line – ABVD (2 cycles) + interim PET/CT

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for combined-modality therapy
1st line – 

ABVD (2 cycles) + interim PET/CT

The goal of treatment for all patients with HL is cure while minimising risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favourable or unfavourable early-stage disease. German Hodgkin Study Group (GHSG) favourable prognosis criteria are most commonly used in the US (mediastinal mass ratio [MMR] <0.33; erythrocyte sedimentation rate [ESR] <50 mm/hour if no B symptoms; ESR <30 mm/hour if B symptoms are present; involvement of ≤2 nodal sites; and no extranodal disease; see Diagnostic criteria).[42][48]

Patients with favourable early-stage disease generally receive two initial cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by an interim PET/CT scan to assess metabolic response and inform subsequent treatment.[32]

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39]

Patients with a Deauville score of 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score of 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

A PET-adapted treatment approach is recommended for all patients with early-stage disease as it offers the opportunity to balance efficacy and toxicity of treatment.​[32][51]​​​[63][64][72][73]

The most effective treatment for early-stage disease is combined-modality therapy, which comprises combination chemotherapy (e.g., ABVD) followed by radiotherapy.[49][50]​​[51][52][53][54][55][56][57][58][59]​ 

A chemotherapy-alone approach may be considered if avoiding radiotherapy is preferred (e.g., due to patient age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[32][60][61][62][63][64]​​​ The decision to omit radiotherapy should involve expert input by a multidisciplinary team, and discussion with the patient regarding risks and benefits. Chemotherapy alone is associated with a slightly lower rate of tumour control and higher rate of relapse compared with combined-modality therapy. Similar survival rates have been reported, but long-term data for overall survival and adverse events are lacking.[49][50]​​​[55][57][59][62][64][65][66][67]​​​​​

HL in older patients (aged >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[45][46][47]​​​​​ Alternative treatment regimens may be considered for patients >60 years, or with poor performance status or substantial comorbidities. Bleomycin should be used with caution; standard regimens may be adapted to remove bleomycin or restrict its use to only two cycles.[32]​​

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – radiotherapy (20 Gy) or ABVD (1 cycle) plus radiotherapy (30 Gy)

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for combined-modality therapy
|
interim PET/CT negative (Deauville score 1 to 2)
Plus – 

radiotherapy (20 Gy) or ABVD (1 cycle) plus radiotherapy (30 Gy)

Treatment recommended for ALL patients in selected patient group

Patients with favourable early-stage disease who are intended for combined-modality therapy and have a Deauville score of 1 to 2 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive 20 Gy radiotherapy (favourable disease on restaging), or one additional cycle of ABVD followed by 30 Gy radiotherapy (unfavourable disease on restaging).[57][58][63][65]

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

Patients should be assessed for suitability for radiotherapy (e.g., based on age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[32] Those deemed unsuitable for radiotherapy can be considered for treatment with chemotherapy alone.

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – radiotherapy (20 Gy) or ABVD (2 cycles) plus radiotherapy (30 Gy)

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for combined-modality therapy
|
interim PET/CT negative (Deauville score 3)
Plus – 

radiotherapy (20 Gy) or ABVD (2 cycles) plus radiotherapy (30 Gy)

Treatment recommended for ALL patients in selected patient group

Patients with favourable early-stage disease who are intended for combined-modality therapy and have a Deauville score of 3 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive 20 Gy radiotherapy (favourable disease on restaging), or two additional cycles of ABVD followed by 30 Gy radiotherapy (unfavourable disease on restaging).[58][63]

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

Patients should be assessed for suitability for radiotherapy (e.g., based on age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[32] Those deemed unsuitable for radiotherapy can be considered for treatment with chemotherapy alone.

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – ABVD (2 cycles) + restaging PET/CT

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for combined-modality therapy
|
interim PET/CT positive (Deauville score 4)
Plus – 

ABVD (2 cycles) + restaging PET/CT

Treatment recommended for ALL patients in selected patient group

Patients with favourable early-stage disease who are intended for combined-modality therapy and have a Deauville score of 4 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive two additional cycles of ABVD followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.[57][63][65]

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39]

Patients with a Deauville score 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Consider – radiotherapy (30 Gy) (if restaging PET/CT negative)

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for combined-modality therapy
|
interim PET/CT positive (Deauville score 4)
Consider – 

radiotherapy (30 Gy) (if restaging PET/CT negative)

Additional treatment recommended for SOME patients in selected patient group

If restaging PET/CT is negative (Deauville score 1 to 3), then 30 Gy radiotherapy can be given.[57][63][65]

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71]​​ ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

Consider – biopsy (if restaging PET/CT positive)

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for combined-modality therapy
|
interim PET/CT positive (Deauville score 4)
Consider – 

biopsy (if restaging PET/CT positive)

Additional treatment recommended for SOME patients in selected patient group

If restaging PET/CT is positive (Deauville score 4 or 5) then a biopsy is recommended to inform subsequent treatment (e.g., salvage therapy).[32]

Plus – biopsy

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for combined-modality therapy
|
interim PET/CT positive (Deauville score 5)
Plus – 

biopsy

Treatment recommended for ALL patients in selected patient group

A biopsy is recommended to inform subsequent treatment (e.g., salvage therapy) for patients with a Deauville score of 5 on interim PET/CT (after two cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]).[32]

early (stage I to II) classical HL: favourable disease and intended for chemotherapy alone

1st line – ABVD (2 cycles) + interim PET/CT

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for chemotherapy alone
1st line – 

ABVD (2 cycles) + interim PET/CT

The goal of treatment for all patients with HL is cure while minimising risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favourable or unfavourable early-stage disease. German Hodgkin Study Group (GHSG) favourable prognosis criteria are most commonly used in the US (mediastinal mass ratio [MMR] <0.33; erythrocyte sedimentation rate [ESR] <50 mm/hour if no B symptoms; ESR <30 mm/hour if B symptoms are present; involvement of ≤2 nodal sites; and no extranodal disease; see Diagnostic criteria).[42][48]​ 

Patients with favourable early-stage disease generally receive two initial cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by an interim PET/CT scan to assess metabolic response and inform subsequent treatment.[32]

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39]

Patients with a Deauville score of 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score of 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

A PET-adapted treatment approach is recommended for all patients with early-stage disease as it offers the opportunity to balance efficacy and toxicity of treatment.​[32][51][63][64][72][73]

The most effective treatment for early-stage disease is combined-modality therapy, which comprises combination chemotherapy (e.g., ABVD) followed by radiotherapy.[49][50]​​[51][52][53][54][55][56][57][58][59]

A chemotherapy-alone approach may be considered if avoiding radiotherapy is preferred (e.g., due to patient age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[32][60][61][62][63][64]​​​ The decision to omit radiotherapy should involve expert input by a multidisciplinary team, and discussion with the patient regarding risks and benefits. Chemotherapy alone is associated with a slightly lower rate of tumour control and higher rate of relapse compared with combined-modality therapy. Similar survival rates have been reported, but long-term data for overall survival and adverse events are lacking.[49][50]​​​[55][57][59][62][64][65][66][67]​​​​​

HL in older patients (aged >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[45][46][47]​​​​​ Alternative treatment regimens may be considered for patients >60 years, or with poor performance status or substantial comorbidities. Bleomycin should be used with caution; standard regimens may be adapted to remove bleomycin or restrict its use to only two cycles.[32]​​

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – ABVD (2 cycles) or AVD (4 cycles)

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for chemotherapy alone
|
interim PET/CT negative (Deauville score 1 to 3)
Plus – 

ABVD (2 cycles) or AVD (4 cycles)

Treatment recommended for ALL patients in selected patient group

Patients with favourable early-stage disease who are intended for chemotherapy alone and have a Deauville score of 1 to 3 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive two additional cycles of ABVD or four additional cycles of AVD (doxorubicin, vinblastine, dacarbazine).[57][62][64][65][66][74]​​

AVD (four cycles) is preferred for Deauville score 3 treated with chemotherapy alone.[32][74]

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

OR

AVD

doxorubicin

and

vinblastine

and

dacarbazine

Plus – ABVD (2 cycles) + restaging PET/CT

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for chemotherapy alone
|
interim PET/CT positive (Deauville score 4)
Plus – 

ABVD (2 cycles) + restaging PET/CT

Treatment recommended for ALL patients in selected patient group

Patients with favourable early-stage disease who are intended for chemotherapy alone and have a Deauville score of 4 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive two additional cycles of ABVD followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.[57][62][64][65]

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39]

Patients with a Deauville score 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Consider – radiotherapy (30 Gy) (if restaging PET/CT negative)

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for chemotherapy alone
|
interim PET/CT positive (Deauville score 4)
Consider – 

radiotherapy (30 Gy) (if restaging PET/CT negative)

Additional treatment recommended for SOME patients in selected patient group

If restaging PET/CT is negative (Deauville score 1 to 3) then 30 Gy radiotherapy should be considered.[57][63][65]

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

Consider – biopsy (if restaging PET/CT positive)

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for chemotherapy alone
|
interim PET/CT positive (Deauville score 4)
Consider – 

biopsy (if restaging PET/CT positive)

Additional treatment recommended for SOME patients in selected patient group

If restaging PET/CT is positive (Deauville score 4 or 5) then a biopsy is recommended to inform subsequent treatment (e.g., salvage therapy).[32]

Plus – biopsy

Back
ACUTE
|
early (stage I to II) classical HL: favourable disease and intended for chemotherapy alone
|
interim PET/CT positive (Deauville score 5)
Plus – 

biopsy

Treatment recommended for ALL patients in selected patient group

A biopsy is recommended to inform subsequent treatment (e.g., salvage therapy) for patients with a Deauville score of 5 on interim PET/CT (after two cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]).[32] 

early (stage I to II) classical HL: unfavourable disease (non-bulky or bulky) and intended for combined-modality therapy

1st line – ABVD (2 cycles) + interim PET/CT

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (non-bulky or bulky) and intended for combined-modality therapy
1st line – 

ABVD (2 cycles) + interim PET/CT

The goal of treatment for all patients with HL is cure while minimising risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favourable or unfavourable early-stage disease. German Hodgkin Study Group (GHSG) favourable prognosis criteria are most commonly used in the US (mediastinal mass ratio [MMR] <0.33; erythrocyte sedimentation rate [ESR] <50 mm/hour if no B symptoms; ESR <30 mm/hour if B symptoms are present; involvement of ≤2 nodal sites; and no extranodal disease; see Diagnostic criteria).[42][48]

Patients with unfavourable early-stage disease generally receive two initial cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by an interim PET/CT scan to assess metabolic response and inform subsequent treatment.

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39]

Patients with a Deauville score of 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score of 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

A PET-adapted treatment approach is recommended for all patients with early-stage disease as it offers the opportunity to balance efficacy and toxicity of treatment.​[32][51][63][64][72][73]

The most effective treatment for early-stage disease is combined-modality therapy, which comprises combination chemotherapy (e.g., ABVD) followed by radiotherapy.[49][50]​​[51][52][53][54][55][56][57][58][59]​​

A chemotherapy-alone approach may be considered if avoiding radiotherapy is preferred (e.g., due to patient age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[32][60][61][62][63][64]​​​ The decision to omit radiotherapy should involve expert input by a multidisciplinary team, and discussion with the patient regarding risks and benefits. Chemotherapy alone is associated with a slightly lower rate of tumour control and higher rate of relapse compared with combined-modality therapy. Similar survival rates have been reported, but long-term data for overall survival and adverse events are lacking.[49][50]​​​[55][57][59][62][64][65][66][67]​​​​​

HL in older patients (aged >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[45][46][47]​​​​​ Alternative treatment regimens may be considered for patients >60 years, or with poor performance status or substantial comorbidities. Bleomycin should be used with caution; standard regimens may be adapted to remove bleomycin or restrict its use to only two cycles.[32]​​

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – ABVD (2 cycles) + radiotherapy (30 Gy)

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (non-bulky or bulky) and intended for combined-modality therapy
|
interim PET/CT negative (Deauville score 1 to 3)
Plus – 

ABVD (2 cycles) + radiotherapy (30 Gy)

Treatment recommended for ALL patients in selected patient group

Patients with unfavourable early-stage disease (non-bulky or bulky) who are intended for combined-modality therapy and have a Deauville score of 1 to 3 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive two additional cycles of ABVD followed by 30 Gy radiotherapy.[51][57][65]

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71]​ ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – ABVD (2 cycles) or BrECADD (2 cycles) + restaging PET/CT

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (non-bulky or bulky) and intended for combined-modality therapy
|
interim PET/CT positive (Deauville score 4 or 5)
Plus – 

ABVD (2 cycles) or BrECADD (2 cycles) + restaging PET/CT

Treatment recommended for ALL patients in selected patient group

Patients with unfavourable early-stage disease (non-bulky or bulky) who are intended for combined-modality therapy and have a Deauville score of 4 or 5 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive two additional cycles of ABVD, or two cycles of BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) with growth factor support, followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.[32][51][57][65][75]​​

BrECADD is recommended for intensive chemotherapy due to its improved safety profile and efficacy compared with escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone); however, evidence is limited in early-stage disease.[32][75]

Growth factor support with a granulocyte colony-stimulating factor (G-CSF) is required for patients treated with BrECADD due to high risk of febrile neutropenia (>20%).​[32][75][79]​ 

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39]

Patients with a Deauville score 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

OR

BrECADD

brentuximab vedotin

and

etoposide

and

cyclophosphamide

and

doxorubicin

and

dacarbazine

and

dexamethasone

Consider – radiotherapy (30 Gy) (if restaging Deauville score 1 to 4)

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (non-bulky or bulky) and intended for combined-modality therapy
|
interim PET/CT positive (Deauville score 4 or 5)
Consider – 

radiotherapy (30 Gy) (if restaging Deauville score 1 to 4)

Additional treatment recommended for SOME patients in selected patient group

If restaging Deauville score is 1 to 4, then 30 Gy radiotherapy can be given.[51][57][65]

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

Consider – biopsy (if restaging Deauville score 5)

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (non-bulky or bulky) and intended for combined-modality therapy
|
interim PET/CT positive (Deauville score 4 or 5)
Consider – 

biopsy (if restaging Deauville score 5)

Additional treatment recommended for SOME patients in selected patient group

If restaging Deauville score is 5, then a biopsy is recommended to inform subsequent treatment (e.g., salvage therapy).[32] 

early (stage I to II) classical HL: unfavourable disease (non-bulky) and intended for chemotherapy alone

1st line – ABVD (2 cycles) + interim PET/CT

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (non-bulky) and intended for chemotherapy alone
1st line – 

ABVD (2 cycles) + interim PET/CT

The goal of treatment for all patients with HL is cure while minimising risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favourable or unfavourable early-stage disease. German Hodgkin Study Group (GHSG) favourable prognosis criteria are most commonly used in the US (mediastinal mass ratio [MMR] <0.33; erythrocyte sedimentation rate [ESR] <50 mm/hour if no B symptoms; ESR <30 mm/hour if B symptoms are present; involvement of ≤2 nodal sites; and no extranodal disease; see Diagnostic criteria).[42][48]

Patients with unfavourable early-stage disease generally receive two initial cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by an interim PET/CT scan to assess metabolic response and inform subsequent treatment.

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39]

Patients with a Deauville score of 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score of 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

A PET-adapted treatment approach is recommended for all patients with early-stage disease as it offers the opportunity to balance efficacy and toxicity of treatment.​[32][51][63]​​​​[64][72][73]

The most effective treatment for early-stage disease is combined-modality therapy, which comprises combination chemotherapy (e.g., ABVD) followed by radiotherapy.[49][50]​​[51][52][53][54][55][56][57][58]​​[59]​​​​ 

A chemotherapy-alone approach may be considered if avoiding radiotherapy is preferred (e.g., due to patient age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[32][60][61][62][63][64]​​​ The decision to omit radiotherapy should involve expert input by a multidisciplinary team, and discussion with the patient regarding risks and benefits. Chemotherapy alone is associated with a slightly lower rate of tumour control and higher rate of relapse compared with combined-modality therapy. Similar survival rates have been reported, but long-term data for overall survival and adverse events are lacking.[49][50]​​​[55][57][59][62][64][65][66][67]​​​​​

HL in older patients (aged >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[45][46][47]​​​​​ Alternative treatment regimens may be considered for patients >60 years, or with poor performance status or substantial comorbidities. Bleomycin should be used with caution; standard regimens may be adapted to remove bleomycin or restrict its use to only two cycles.[32]​​

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – ABVD (2 cycles) or AVD (4 cycles)

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (non-bulky) and intended for chemotherapy alone
|
interim PET/CT negative (Deauville score 1 to 3)
Plus – 

ABVD (2 cycles) or AVD (4 cycles)

Treatment recommended for ALL patients in selected patient group

Patients with unfavourable early-stage disease (non-bulky) who are intended for chemotherapy alone and have a Deauville score of 1 to 3 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive two additional cycles of ABVD or four additional cycles of AVD (doxorubicin, vinblastine, dacarbazine).[66]

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

OR

AVD

doxorubicin

and

vinblastine

and

dacarbazine

Plus – ABVD (2 cycles) or BrECADD (2 cycles) + restaging PET/CT

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (non-bulky) and intended for chemotherapy alone
|
interim PET/CT positive (Deauville score 4 or 5)
Plus – 

ABVD (2 cycles) or BrECADD (2 cycles) + restaging PET/CT

Treatment recommended for ALL patients in selected patient group

Patients with unfavourable early-stage disease (non-bulky) who are intended for chemotherapy alone and have a Deauville score of 4 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive two additional cycles of ABVD, or two cycles of BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) with growth factor support, followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.[32][57][62][64][65][75]

BrECADD is recommended for intensive chemotherapy due to its improved safety profile and efficacy compared with escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone); however, evidence is limited in early-stage disease.[32][75] 

Growth factor support with a granulocyte colony-stimulating factor (G-CSF) is required for patients treated with BrECADD due to high risk of febrile neutropenia (>20%).[32][75][79]

​​Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39]

Patients with a Deauville score 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

OR

BrECADD

brentuximab vedotin

and

etoposide

and

cyclophosphamide

and

doxorubicin

and

dacarbazine

and

dexamethasone

Consider – radiotherapy (30 Gy) (if restaging Deauville score 1 to 4)

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (non-bulky) and intended for chemotherapy alone
|
interim PET/CT positive (Deauville score 4 or 5)
Consider – 

radiotherapy (30 Gy) (if restaging Deauville score 1 to 4)

Additional treatment recommended for SOME patients in selected patient group

If restaging Deauville score is 1 to 4, then 30 Gy radiotherapy should be considered.[57][63][65]

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71]​ ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

Consider – biopsy (if restaging Deauville score 5)

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (non-bulky) and intended for chemotherapy alone
|
interim PET/CT positive (Deauville score 4 or 5)
Consider – 

biopsy (if restaging Deauville score 5)

Additional treatment recommended for SOME patients in selected patient group

If restaging Deauville score is 5, then a biopsy is recommended to inform subsequent treatment (e.g., salvage therapy).[32] 

early (stage I to II) classical HL: unfavourable disease (bulky) and intended for chemotherapy alone

1st line – ABVD (2 cycles) + interim PET/CT

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (bulky) and intended for chemotherapy alone
1st line – 

ABVD (2 cycles) + interim PET/CT

The goal of treatment for all patients with HL is cure while minimising risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favourable or unfavourable early-stage disease. German Hodgkin Study Group (GHSG) favourable prognosis criteria are most commonly used in the US (mediastinal mass ratio [MMR] <0.33; erythrocyte sedimentation rate [ESR] <50 mm/hour if no B symptoms; ESR <30 mm/hour if B symptoms are present; involvement of ≤2 nodal sites; and no extranodal disease; see Diagnostic criteria).[42][48]

Patients with unfavourable early-stage disease generally receive two initial cycles of ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) followed by an interim PET/CT scan to assess metabolic response and inform subsequent treatment.

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39]

Patients with a Deauville score of 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score of 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

A PET-adapted treatment approach is recommended for all patients with early-stage disease as it offers the opportunity to balance efficacy and toxicity of treatment.​[32][51]​​​​[63][64][72][73]

The most effective treatment for early-stage disease is combined-modality therapy, which comprises combination chemotherapy (e.g., ABVD) followed by radiotherapy.[49][50]​​[51][52][53][54][55][56][57][58][59]​​​ 

A chemotherapy-alone approach may be considered if avoiding radiotherapy is preferred (e.g., due to patient age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[32][60][61][62][63][64]​​​ The decision to omit radiotherapy should involve expert input by a multidisciplinary team, and discussion with the patient regarding risks and benefits. Chemotherapy alone is associated with a slightly lower rate of tumour control and higher rate of relapse compared with combined-modality therapy. Similar survival rates have been reported, but long-term data for overall survival and adverse events are lacking.[49][50]​​​[55][57][59][62][64][65][66][67]​​​​​

HL in older patients (aged >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[45][46][47]​​​​​ Alternative treatment regimens may be considered for patients >60 years, or with poor performance status or substantial comorbidities. Bleomycin should be used with caution; standard regimens may be adapted to remove bleomycin or restrict its use to only two cycles.[32]​​​

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – AVD (4 cycles)

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (bulky) and intended for chemotherapy alone
|
interim PET/CT negative (Deauville score 1 to 3)
Plus – 

AVD (4 cycles)

Treatment recommended for ALL patients in selected patient group

Patients with unfavourable early-stage disease (bulky) who are intended for chemotherapy alone and have a Deauville score of 1 to 3 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive four additional cycles of AVD (doxorubicin, vinblastine, dacarbazine).[66]

See local specialist protocol for dosing guidelines.

Primary options

AVD

doxorubicin

and

vinblastine

and

dacarbazine

Plus – ABVD (2 cycles) or BrECADD (2 cycles) + restaging PET/CT

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (bulky) and intended for chemotherapy alone
|
interim PET/CT positive (Deauville score 4 or 5)
Plus – 

ABVD (2 cycles) or BrECADD (2 cycles) + restaging PET/CT

Treatment recommended for ALL patients in selected patient group

Patients with unfavourable early-stage disease (bulky) who are intended for chemotherapy alone and have a Deauville score of 4 or 5 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive two additional cycles of ABVD, or two cycles of BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) with growth factor support (granulocyte colony-stimulating factor), followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.[51][57][66][135][136]

BrECADD is recommended for intensive chemotherapy due to its improved safety profile and efficacy compared with escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone); however, evidence is limited in early-stage disease.[32][75] 

Growth factor support with a granulocyte colony-stimulating factor (G-CSF) is required for patients treated with BrECADD due to high risk of febrile neutropenia (>20%).[32]​​[75][79]​ 

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39]

Patients with a Deauville score 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

OR

BrECADD

brentuximab vedotin

and

etoposide

and

cyclophosphamide

and

doxorubicin

and

dacarbazine

and

dexamethasone

Consider – radiotherapy (30 Gy) (if restaging Deauville score 1 to 4)

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (bulky) and intended for chemotherapy alone
|
interim PET/CT positive (Deauville score 4 or 5)
Consider – 

radiotherapy (30 Gy) (if restaging Deauville score 1 to 4)

Additional treatment recommended for SOME patients in selected patient group

If restaging Deauville score is 1 to 4, then 30 Gy radiotherapy can be given.[51][57][65] 

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

Consider – biopsy (if restaging Deauville score 5)

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease (bulky) and intended for chemotherapy alone
|
interim PET/CT positive (Deauville score 4 or 5)
Consider – 

biopsy (if restaging Deauville score 5)

Additional treatment recommended for SOME patients in selected patient group

If restaging Deauville score is 5, then a biopsy is recommended to inform subsequent treatment (e.g., salvage therapy).[32]

early (stage I to II) classical HL: unfavourable disease and intended for alternative induction therapy

1st line – nivolumab + AVD (4 cycles) + radiotherapy (30 Gy)

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease and intended for alternative induction therapy
1st line – 

nivolumab + AVD (4 cycles) + radiotherapy (30 Gy)

The goal of treatment for all patients with HL is cure while minimising risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favourable or unfavourable early-stage disease. German Hodgkin Study Group (GHSG) favourable prognosis criteria are most commonly used in the US (mediastinal mass ratio [MMR] <0.33; erythrocyte sedimentation rate [ESR] <50 mm/hour if no B symptoms; ESR <30 mm/hour if B symptoms are present; involvement of ≤2 nodal sites; and no extranodal disease; see Diagnostic criteria).[42][48]

National Comprehensive Cancer Network (NCCN) guidelines suggest consideration of alternative initial treatment regimens (chemoimmunotherapy or intensive chemotherapy without initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) for certain patients with unfavourable early-stage HL, although evidence in this patient group is lacking.[32] 

Nivolumab (an anti-programmed death-1 [PD-1] monoclonal antibody) plus AVD (doxorubicin plus vinblastine plus dacarbazine) for four cycles followed by 30 Gy radiotherapy may be considered for patients with B symptoms and/or bulky disease.​[76][77]

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

See local specialist protocol for dosing guidelines.

Primary options

Nivolumab + AVD

nivolumab

and

doxorubicin

and

vinblastine

and

dacarbazine

1st line – brentuximab vedotin + AVD (4 cycles) + radiotherapy (30 Gy)

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease and intended for alternative induction therapy
1st line – 

brentuximab vedotin + AVD (4 cycles) + radiotherapy (30 Gy)

The goal of treatment for all patients with HL is cure while minimising risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favourable or unfavourable early-stage disease. German Hodgkin Study Group (GHSG) favourable prognosis criteria are most commonly used in the US (mediastinal mass ratio [MMR] <0.33; erythrocyte sedimentation rate [ESR] <50 mm/hour if no B symptoms; ESR <30 mm/hour if B symptoms are present; involvement of ≤2 nodal sites; and no extranodal disease; see Diagnostic criteria).[42][48] 

National Comprehensive Cancer Network (NCCN) guidelines suggest consideration of alternative initial treatment regimens (chemoimmunotherapy or intensive chemotherapy without initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) for certain patients with unfavourable early-stage HL, although evidence in this patient group is lacking.[32]

Brentuximab vedotin (an anti-CD30 monoclonal antibody conjugated to monomethyl auristatin E) plus AVD (doxorubicin plus vinblastine plus dacarbazine) with growth factor support for four cycles, followed by 30 Gy radiotherapy, may be considered for patients with B symptoms and bulky disease.[78] 

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

Growth factor support with a granulocyte colony-stimulating factor (G-CSF) is required for patients treated with brentuximab vedotin plus AVD due to high risk of febrile neutropenia (>20%).[32][79][80] 

See local specialist protocol for dosing guidelines.

Primary options

Brentuximab vedotin + AVD

brentuximab vedotin

and

doxorubicin

and

vinblastine

and

dacarbazine

1st line – BrECADD (2 cycles) + interim PET/CT ± BrECADD (up to 6 cycles in total)

Back
ACUTE
|
early (stage I to II) classical HL: unfavourable disease and intended for alternative induction therapy
1st line – 

BrECADD (2 cycles) + interim PET/CT ± BrECADD (up to 6 cycles in total)

The goal of treatment for all patients with HL is cure while minimising risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favourable or unfavourable early-stage disease. German Hodgkin Study Group (GHSG) favourable prognosis criteria are most commonly used in the US (mediastinal mass ratio [MMR] <0.33; erythrocyte sedimentation rate [ESR] <50 mm/hour if no B symptoms; ESR <30 mm/hour if B symptoms are present; involvement of ≤2 nodal sites; and no extranodal disease; see Diagnostic criteria).[42][48] 

National Comprehensive Cancer Network (NCCN) guidelines suggest consideration of alternative initial treatment regimens (chemoimmunotherapy or intensive chemotherapy without initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) for certain patients with unfavourable early-stage HL, although evidence in this patient group is lacking.[32] 

BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) with growth factor support may be considered for patients with bulky disease with either B symptoms or extranodal disease, aged 18-61 years, using a PET-adapted treatment approach.[75] Initial treatment with two cycles is followed by an interim PET/CT scan to assess metabolic response and inform subsequent management (further cycles of BrECADD up to a total of six cycles).

Growth factor support with a granulocyte colony-stimulating factor (G-CSF) is required for patients treated with BrECADD due to high risk of febrile neutropenia (>20%).[32][75][79] 

See local specialist protocol for dosing guidelines.

Primary options

BrECADD

brentuximab vedotin

and

etoposide

and

cyclophosphamide

and

doxorubicin

and

dacarbazine

and

dexamethasone

advanced (stage III to IV) classical HL: intended for intensive induction chemotherapy

1st line – BrECADD (2 cycles) + interim PET/CT

Back
ACUTE
|
advanced (stage III to IV) classical HL: intended for intensive induction chemotherapy
1st line – 

BrECADD (2 cycles) + interim PET/CT

The goal of treatment for all patients with HL is cure while minimising risk of toxicity and long-term complications.

BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) is a preferred initial treatment option for patients with advanced-stage disease.[32][75] 

BrECADD is an intensive chemotherapy regimen that offers lower treatment-related morbidity and improved progression-free survival compared with escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisolone) in patients with advanced-stage disease.[75] 

BrECADD is not recommended for older patients (aged ≥61 years).

A PET-adapted treatment approach is used in patients receiving BrECADD for advanced-stage disease to guide treatment decisions regarding escalation or de-escalation of chemotherapy.[32][33][75]​​[89]

Patients typically receive two initial cycles of BrECADD with growth factor support, followed by an interim PET/CT scan to assess metabolic response and inform subsequent treatment.

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39] 

Patients with a Deauville score of 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score of 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

Growth factor support with a granulocyte colony-stimulating factor (G-CSF) is required for patients treated with BrECADD due to high risk of febrile neutropenia (>20%).[32][75][79] 

See local specialist protocol for dosing guidelines.

Primary options

BrECADD

brentuximab vedotin

and

etoposide

and

cyclophosphamide

and

doxorubicin

and

dacarbazine

and

dexamethasone

Plus – BrECADD (2 cycles) + restaging PET/CT ± radiotherapy

Back
ACUTE
|
advanced (stage III to IV) classical HL: intended for intensive induction chemotherapy
|
interim PET/CT negative (Deauville score 1 to 3)
Plus – 

BrECADD (2 cycles) + restaging PET/CT ± radiotherapy

Treatment recommended for ALL patients in selected patient group

Patients with a Deauville score of 1 to 3 on interim PET/CT (after two initial cycles of BrECADD [brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone]) can receive two additional cycles of BrECADD with growth factor support, followed by restaging PET/CT to assess metabolic response and inform subsequent management.[32][75]

Growth factor support with a granulocyte colony-stimulating factor (G-CSF) is required for patients treated with BrECADD due to high risk of febrile neutropenia (>20%).[32][75][79] 

Consolidation radiotherapy (30 to 36 Gy) may be considered for patients with residual PET-positive disease following completion of initial treatment with chemotherapy.

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71]​​ ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

See local specialist protocol for dosing guidelines.

Primary options

BrECADD

brentuximab vedotin

and

etoposide

and

cyclophosphamide

and

doxorubicin

and

dacarbazine

and

dexamethasone

Plus – biopsy + BrECADD (4 cycles) ± radiotherapy (if biopsy negative) or salvage therapy (if biopsy positive)

Back
ACUTE
|
advanced (stage III to IV) classical HL: intended for intensive induction chemotherapy
|
interim PET/CT positive (Deauville score 4 or 5)
Plus – 

biopsy + BrECADD (4 cycles) ± radiotherapy (if biopsy negative) or salvage therapy (if biopsy positive)

Treatment recommended for ALL patients in selected patient group

Patients with advanced-stage disease who have a Deauville score of 4 or 5 on interim PET/CT (after two initial cycles of BrECADD [brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone]) should have a biopsy to inform subsequent treatment.

Patients with a negative biopsy can receive four additional cycles of BrECADD with growth factor support followed by a restaging PET/CT scan.[32][75] 

Patients with a positive biopsy may require salvage therapy.

Growth factor support with a granulocyte colony-stimulating factor (G-CSF) is required for patients treated with BrECADD due to high risk of febrile neutropenia (>20%).[32][75][79]

Consolidation radiotherapy (30 to 36 Gy) may be considered for patients with residual PET-positive disease following completion of initial treatment with chemotherapy.

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

See local specialist protocol for dosing guidelines.

Primary options

BrECADD

brentuximab vedotin

and

etoposide

and

cyclophosphamide

and

doxorubicin

and

dacarbazine

and

dexamethasone

advanced (stage III to IV) classical HL: intended for standard induction therapy (chemoimmunotherapy)

1st line – nivolumab + AVD (6 cycles)

Back
ACUTE
|
advanced (stage III to IV) classical HL: intended for standard induction therapy (chemoimmunotherapy)
1st line – 

nivolumab + AVD (6 cycles)

The goal of treatment for all patients with HL is cure while minimising risk of toxicity and long-term complications.

Nivolumab (an anti-programmed death-1 [PD-1] monoclonal antibody) plus AVD (doxorubicin, vinblastine, dacarbazine) is a preferred initial treatment for patients with advanced-stage disease.[32][88] 

Nivolumab plus AVD appears to be well-tolerated, and may be an option for older patients (age >60 years) suitable for multi-agent chemotherapy with advanced disease.[32] 

Patients typically receive six cycles of nivolumab plus AVD, followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.[32] 

Improved progression-free survival (92% vs. 83%; median follow-up 2.1 years) and lower rates of peripheral neuropathy and treatment discontinuation were demonstrated with nivolumab plus AVD compared with brentuximab vedotin plus AVD in one randomised phase 3 trial.[88] 

Growth factor support was optional in clinical trials.

See local specialist protocol for dosing guidelines.

Primary options

Nivolumab + AVD

nivolumab

and

doxorubicin

and

vinblastine

and

dacarbazine

1st line – brentuximab vedotin + AVD (6 cycles)

Back
ACUTE
|
advanced (stage III to IV) classical HL: intended for standard induction therapy (chemoimmunotherapy)
1st line – 

brentuximab vedotin + AVD (6 cycles)

The goal of treatment for all patients with HL is cure while minimising risk of toxicity and long-term complications.

Initial treatment options for advanced-stage disease include brentuximab vedotin (an anti-CD30 monoclonal antibody conjugated to monomethyl auristatin E) plus AVD (doxorubicin, vinblastine, dacarbazine) with growth factor support.[32]

Patients typically receive six cycles of brentuximab vedotin plus AVD with growth factor support, followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment (e.g., salvage therapy).

Caution is required when used in older patients (aged >60 years) and it is contraindicated in patients with neuropathy.[32]

For older patients, sequential brentuximab vedotin plus AVD may be a preferred option.[87] This involves administering 2 cycles of brentuximab vedotin followed by 6 cycles of AVD followed by 4 cycles of brentuximab vedotin.[87] 

Brentuximab vedotin plus AVD offers a survival advantage compared with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in patients with advanced-stage disease.[32][90][91][92]

 Growth factor support with a granulocyte colony-stimulating factor (G-CSF) is required for patients treated with brentuximab vedotin plus AVD due to high risk of febrile neutropenia (>20%).[32][79][80] 

See local specialist protocol for dosing guidelines.

Primary options

Brentuximab vedotin + AVD

brentuximab vedotin

and

doxorubicin

and

vinblastine

and

dacarbazine

advanced (stage III to IV) classical HL: intended for standard induction therapy (chemotherapy)

1st line – ABVD (2 cycles) + interim PET/CT

Back
ACUTE
|
advanced (stage III to IV) classical HL: intended for standard induction therapy (chemotherapy)
1st line – 

ABVD (2 cycles) + interim PET/CT

The goal of treatment for all patients with HL is cure while minimising risk of toxicity and long-term complications.

Initial treatment options for advanced-stage disease include ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). ABVD may be an option for advanced disease if other treatment options are not available or are contraindicated.[32]

A PET-adapted treatment approach is used in patients receiving ABVD with advanced-stage disease to guide treatment decisions regarding escalation or de-escalation of chemotherapy.[32][66][89]​​

Patients typically receive two initial cycles of ABVD, followed by an interim PET/CT scan to assess metabolic response and inform subsequent treatment.[66] 

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39]​​

Patients with a Deauville score of 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score of 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

HL in older patients (aged >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[45][46][47] Alternative treatment regimens may be considered for patients >60 years, or with poor performance status or substantial comorbidities. Bleomycin should be used with caution; standard regimens may be adapted to remove bleomycin or restrict its use to only two cycles.[32]

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – AVD (4 cycles)

Back
ACUTE
|
advanced (stage III to IV) classical HL: intended for standard induction therapy (chemotherapy)
|
interim PET/CT negative (Deauville score 1 to 3)
Plus – 

AVD (4 cycles)

Treatment recommended for ALL patients in selected patient group

Patients with advanced-stage disease who have a Deauville score of 1 to 3 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive four additional cycles of AVD (doxorubicin, vinblastine, dacarbazine).[32][66] 

See local specialist protocol for dosing guidelines.

Primary options

AVD

doxorubicin

and

vinblastine

and

dacarbazine

Plus – BrECADD (3 cycles) + restaging PET/CT

Back
ACUTE
|
advanced (stage III to IV) classical HL: intended for standard induction therapy (chemotherapy)
|
interim PET/CT positive (Deauville score 4 or 5)
Plus – 

BrECADD (3 cycles) + restaging PET/CT

Treatment recommended for ALL patients in selected patient group

Patients with advanced-stage disease who have a Deauville score of 4 or 5 on interim PET/CT (after two initial cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine]) can receive three additional cycles of BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) with growth factor support, followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[39] 

Patients with a Deauville score of 1 to 3 (i.e., negative PET/CT) are considered to have a complete metabolic response. Patients with a Deauville score of 4 or 5 (i.e., positive PET/CT) are considered to have a partial metabolic response (see Diagnostic criteria).

Growth factor support with a granulocyte colony-stimulating factor (G-CSF) is required for patients treated with BrECADD due to high risk of febrile neutropenia (>20%).[32][75][79] 

See local specialist protocol for dosing guidelines.

Primary options

BrECADD

brentuximab vedotin

and

etoposide

and

cyclophosphamide

and

doxorubicin

and

dacarbazine

and

dexamethasone

Consider – BrECADD (1 cycle) (± radiotherapy) or biopsy

Back
ACUTE
|
advanced (stage III to IV) classical HL: intended for standard induction therapy (chemotherapy)
|
interim PET/CT positive (Deauville score 4 or 5)
Consider – 

BrECADD (1 cycle) (± radiotherapy) or biopsy

Additional treatment recommended for SOME patients in selected patient group

If restaging PET/CT is negative (Deauville score 1 to 3) then one additional cycle of BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) with growth factor support can be given.

Growth factor support with a granulocyte colony-stimulating factor (G-CSF) is required for patients treated with BrECADD due to high risk of febrile neutropenia (>20%).[32][75][79]

If restaging PET/CT is positive (Deauville score 4 or 5), then a biopsy is recommended to inform subsequent treatment (e.g., salvage therapy).

Consolidation radiotherapy (i.e., after initial chemotherapy) may be considered for patients following completion of initial treatment with chemotherapy.

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

See local specialist protocol for dosing guidelines.

Primary options

BrECADD

brentuximab vedotin

and

etoposide

and

cyclophosphamide

and

doxorubicin

and

dacarbazine

and

dexamethasone

asymptomatic early (stage IA to IIA) NLPHL, non-bulky disease

1st line – radiotherapy (30-36 Gy) or observation

Back
ACUTE
|
asymptomatic early (stage IA to IIA) NLPHL, non-bulky disease
1st line – 

radiotherapy (30-36 Gy) or observation

Nodular lymphocyte-predominant HL (NLPHL) is a rare subtype of HL.

Most patients with NLPHL present with early-stage disease involving peripheral nodal regions (e.g., groin, axilla, neck).

The goal of treatment is cure while minimising risk of late effects. Overall prognosis for patients with early-stage NLPHL is excellent.

Radiotherapy alone at a dose 30 to 36 Gy is recommended for most patients with asymptomatic early (stage IA and IIA) non-bulky NLPHL.[32][68][125]

Involved-site radiotherapy (ISRT) is the preferred approach (although most available data are for involved-field radiotherapy [IFRT]).[68]

ISRT focuses radiation only on involved lymph nodes and nearby sites rather than lymph node regions (which is done with IFRT), therefore minimising radiation exposure to uninvolved structures and reduces the risk of adverse effects.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Most patients receiving treatment to the mediastinum develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

Retrospective studies have reported excellent remission and survival outcomes with radio therapy alone for early-stage NLPHL.[126][127][128][129] Randomised trials of treatments for NLPHL are lacking due to the rarity of this disease subtype.

Observation may be appropriate for patients with asymptomatic early-stage non-bulky disease, particularly if there is concern regarding toxicity related to radiotherapy.[130] Observation is also an option for selected patients with stage IA non-bulky disease who have a completely excised solitary lymph node.[32]

asymptomatic early (stage IA to IIA) NLPHL, bulky disease; and symptomatic early (stage IB to IIB) NLPHL

1st line – rituximab + chemotherapy + radiotherapy; or observation (if asymptomatic); or palliative rituximab alone

Back
ACUTE
|
asymptomatic early (stage IA to IIA) NLPHL, bulky disease; and symptomatic early (stage IB to IIB) NLPHL
1st line – 

rituximab + chemotherapy + radiotherapy; or observation (if asymptomatic); or palliative rituximab alone

Nodular lymphocyte-predominant HL (NLPHL) is a rare subtype of HL.

Most patients with NLPHL present with early-stage disease involving peripheral nodal regions (e.g., groin, axilla, neck).

The goal of treatment is cure while minimising risk of late effects. Overall prognosis for patients with early-stage NLPHL is excellent.

Systemic treatment with rituximab plus combination chemotherapy (e.g., R-ABVD [rituximab, doxorubicin, bleomycin, vinblastine, dacarbazine], R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone], or R-CVbP [rituximab, cyclophosphamide, vinblastine, prednisolone]) followed by radiotherapy (30 to 36 Gy) is recommended for patients with asymptomatic early (stage IA and IIA) bulky NLPHL, and those with symptomatic early NLPHL (stage IB to IIB).[32]​​​[125][131]

The CD20 antigen is present on most NLPHL cells; therefore, anti-CD20 treatment with rituximab is a key component of systemic treatment for NLPHL.

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

Observation may be appropriate for patients with asymptomatic early-stage bulky disease, particularly if there is concern regarding toxicity related to systemic treatment and radiotherapy.[130]

Rituximab alone may be an option for palliation in select patients (e.g., stage IIA non-contiguous disease).[32]

See local specialist protocol for dosing guidelines.

Primary options

R-ABVD

rituximab

and

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

OR

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

OR

R-CVbP

rituximab

and

cyclophosphamide

and

vinblastine

and

prednisolone

OR

Rituximab alone

rituximab

advanced (stage III to IV) NLPHL

1st line – observation; or rituximab + chemotherapy (± radiotherapy); or palliative therapy

Back
ACUTE
|
advanced (stage III to IV) NLPHL
1st line – 

observation; or rituximab + chemotherapy (± radiotherapy); or palliative therapy

Observation may be appropriate for patients with asymptomatic advanced-stage disease.[32][125]

Systemic treatment with rituximab plus combination chemotherapy (e.g., R-ABVD [rituximab, doxorubicin, bleomycin, vinblastine, dacarbazine], R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone], or R-CVbP [rituximab, cyclophosphamide, vinblastine, prednisolone]) with or without radiotherapy is recommended for patients with symptomatic advanced-stage disease or rapid progression.[32][132][133]​ 

Rituximab alone or local radiotherapy may be options for palliation in select patients.[32]

The CD20 antigen is present on most NLPHL cells; therefore, anti-CD20 treatment with rituximab is a key component of systemic treatment for NLPHL.

Involved-site radiotherapy (ISRT) is preferred to traditional involved-field radiotherapy (IFRT) due to its lower risk of adverse effects.[68][69][70][71]​ ISRT focuses radiation only on involved lymph nodes and nearby sites, minimising radiation exposure to uninvolved structures.

Acute adverse effects of radiotherapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop oesophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiotherapy can cause nausea and/or diarrhoea. Fatigue is common in all patients receiving radiotherapy. Possible long-term adverse effects of radiotherapy include secondary malignancies, cardiovascular disease, and decreased pulmonary function.

See local specialist protocol for dosing guidelines.

Primary options

R-ABVD

rituximab

and

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

OR

R-CHOP

rituximab

and

cyclophosphamide

and

doxorubicin

and

vincristine

and

prednisolone

OR

R-CVbP

rituximab

and

cyclophosphamide

and

vinblastine

and

prednisolone

OR

Rituximab alone

rituximab

ONGOING

refractory or relapsed classical HL

1st line – salvage therapy + PET/CT

Back
ONGOING
|
refractory or relapsed classical HL
1st line – 

salvage therapy + PET/CT

Refractory or relapsed HL should be confirmed with biopsy.

Treatment for refractory or relapsed HL must be individualised, taking into consideration factors such as previous first-line treatment, patient age, medical comorbidities, duration of first remission, and stage at relapse. The goal of treatment, at least initially, is cure.

Referral to a centre with expertise is recommended; clinical trials should be considered, where possible.[32]

Salvage therapy, followed by high-dose chemotherapy (for conditioning) and autologous stem cell transplantation (ASCT), is the standard approach for most patients who relapse following first-line treatment.[32][93][94][95][96][97] 

The role of salvage therapy is to reduce tumour burden and mobilise stem cells before conditioning and ASCT.[32]

Combination chemotherapy or chemoimmunotherapy regimens can be used for salvage therapy. The optimal salvage regimen is unclear due to the lack of head-to-head randomised trials.

The following chemoimmunotherapy regimens including a checkpoint inhibitor (nivolumab or pembrolizumab) are preferred for patients with no prior exposure to these agents: nivolumab plus ICE (ifosfamide, carboplatin, etoposide); nivolumab plus brentuximab vedotin; pembrolizumab plus GVD (gemcitabine, vinorelbine, pegylated liposomal doxorubicin); pembrolizumab plus ICE.[32][106][107][108][109]

The following regimens (without a checkpoint inhibitor) are commonly used: BeGEV (bendamustine, gemcitabine, vinorelbine); brentuximab vedotin; brentuximab vedotin plus bendamustine; brentuximab vedotin plus ICE; DHAP (dexamethasone, cytarabine, cisplatin); GVD; ICE; IGEV (ifosfamide, gemcitabine, vinorelbine).[96][97][110][111][112][113][114]​​

A PET-adapted treatment approach is used for refractory or relapsed HL in order to optimise outcomes following stem cell transplantation. A negative pre-transplantation PET/CT (Deauville score 1 to 3) is associated with optimal outcomes following transplantation and should, therefore, be the goal of salvage therapy prior to ASCT.[117][118]​ Patients with a positive PET/CT (Deauville score 4 or 5) following salvage therapy may be considered for a different salvage regimen to achieve a negative PET/CT.[119][120][121]

See local specialist protocol for dosing guidelines.

Primary options

Nivolumab + ICE

nivolumab

and

ifosfamide

and

carboplatin

and

etoposide

OR

Nivolumab + brentuximab vedotin

nivolumab

and

brentuximab vedotin

OR

Pembrolizumab + GVD

pembrolizumab

and

gemcitabine

and

vinorelbine

and

doxorubicin liposomal

OR

Pembrolizumab + ICE

pembrolizumab

and

ifosfamide

and

carboplatin

and

etoposide

Secondary options

BeGEV

bendamustine

and

gemcitabine

and

vinorelbine

OR

Brentuximab vedotin alone

brentuximab vedotin

OR

Brentuximab vedotin + bendamustine

brentuximab vedotin

and

bendamustine

OR

Brentuximab vedotin + ICE

brentuximab vedotin

and

ifosfamide

and

carboplatin

and

etoposide

OR

DHAP

dexamethasone

and

cytarabine

and

cisplatin

OR

GVD

gemcitabine

and

vinorelbine

and

doxorubicin liposomal

OR

ICE

ifosfamide

and

carboplatin

and

etoposide

OR

IGEV

ifosfamide

and

gemcitabine

and

vinorelbine

Consider – conditioning + stem cell transplantation (if PET/CT negative)

Back
ONGOING
|
refractory or relapsed classical HL
Consider – 

conditioning + stem cell transplantation (if PET/CT negative)

Additional treatment recommended for SOME patients in selected patient group

Patients with relapsed or refractory disease who are PET/CT negative (Deauville score 1 to 3) following salvage therapy can be considered for high-dose chemotherapy (for conditioning) and autologous stem cell transplantation (ASCT).[93][94][95][96][97]

Radiotherapy may be used alongside high-dose chemotherapy (as part of conditioning) in eligible patients.

Allogeneic stem cell transplantation (AlloSCT) may be considered in patients who relapse after ASCT, offering a potentially curative option.​[102]​​[103][104][105]

In selected patients, radiotherapy alone or chemotherapy alone is appropriate following salvage therapy.[99][100]

Consider – brentuximab vedotin (maintenance)

Back
ONGOING
|
refractory or relapsed classical HL
Consider – 

brentuximab vedotin (maintenance)

Additional treatment recommended for SOME patients in selected patient group

Brentuximab vedotin (an anti-CD30 monoclonal antibody conjugated to monomethyl auristatin E) is recommended as consolidation/maintenance therapy following autologous stem cell transplantation in patients at high risk for relapse (e.g., refractory to initial treatment; with relapse within 12 months following initial treatment; with B symptoms; PET/CT-positive at transplant; and/or with extranodal disease) with no prior brentuximab vedotin therapy.[32][123][124][122]

Maintenance brentuximab vedotin is recommended for 16 cycles or until unacceptable toxicity or relapse (whichever occurs first).[123]

See local specialist protocol for dosing guidelines.

Primary options

brentuximab vedotin

refractory or relapsed NLPHL

1st line – salvage therapy or observation

Back
ONGOING
|
refractory or relapsed NLPHL
1st line – 

salvage therapy or observation

Refractory or relapsed NLPHL should be confirmed by biopsy to rule out transformation to aggressive non-Hodgkin's lymphoma.

Treatment for refractory or relapsed NLPHL must be individualised, taking into consideration factors such as previous first-line treatment (e.g., R-ABVD [rituximab, doxorubicin, bleomycin, vinblastine, dacarbazine] with radiotherapy), patient age, medical comorbidities, duration of first remission, and stage at relapse.[125]

Salvage therapy with a rituximab-based chemotherapy regimen or rituximab alone is the preferred approach for most patients with refractory or relapsed NLPHL. Observation may be considered for asymptomatic patients as an initial approach.[32] Autologous stem cell transplantation (ASCT) may be considered for patients with aggressive disease.

The optimal regimen for salvage chemotherapy is unclear, but the following rituximab-based regimens can be considered if not previously used: R-ABVD; R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone); R-CVbP (rituximab, cyclophosphamide, vinblastine, prednisolone); rituximab plus bendamustine; R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin); R-ICE (rituximab, ifosfamide, carboplatin, etoposide); or R-IGEV (rituximab, ifosfamide, gemcitabine, vinorelbine).

Radiotherapy may be considered in combination with systemic therapy for patients who are symptomatic or with high tumour burden disease.[32]

Rituximab alone can be considered for patients who relapse with limited stage disease and low tumour volume.[32][134] 

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