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: favorable disease and intended for combined-modality therapy

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

Back
ACUTE
|
early (stage I to II) classical HL: favorable 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 minimizing risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favorable or unfavorable early-stage disease. German Hodgkin Study Group (GHSG) favorable 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).[44][50]

Patients with favorable 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.[33]

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[40]

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.[5][33][54][65][66][74][75]

The most effective treatment for early-stage disease is combined-modality therapy, which comprises combination chemotherapy (e.g., ABVD) followed by radiation therapy.[51][52][53][54][55][56][57][58][59][60][61]​ 

A chemotherapy-alone approach may be considered if avoiding radiation therapy is preferred (e.g., due to patient age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[33][62][63][64][65][66]​ The decision to omit radiation therapy 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 tumor control and higher rate of relapse compared with combined-modality therapy, but survival rates are similar.[51][52][53][58][60][64][66][67][68][69] [ Cochrane Clinical Answers logo ]

HL in older patients (ages >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[46][47][48]​​ 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.[49]

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

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

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

radiation therapy (20 Gy) or ABVD (1 cycle) plus radiation therapy (30 Gy)

Treatment recommended for ALL patients in selected patient group

Patients with favorable 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) can receive 20 Gy radiation therapy, or one additional cycle of ABVD followed by 30 Gy radiation therapy.[60][61][65][67]

Involved-site radiation therapy (ISRT) is preferred to traditional involved-field radiation therapy (IFRT) due to its lower risk of adverse effects.[70][71][72][73] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimizing radiation exposure to uninvolved structures.

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

Patients should be assessed for suitability for radiation therapy (e.g., based on age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[33] Those deemed unsuitable for radiation therapy 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 – radiation therapy (20 Gy) or ABVD (2 cycles) plus radiation therapy (30 Gy)

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

radiation therapy (20 Gy) or ABVD (2 cycles) plus radiation therapy (30 Gy)

Treatment recommended for ALL patients in selected patient group

Patients with favorable 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) can receive 20 Gy radiation therapy, or two additional cycle of ABVD followed by 30 Gy radiation therapy (based on the RAPID study).[61][65]​​

Involved-site radiation therapy (ISRT) is preferred to traditional involved-field radiation therapy (IFRT) due to its lower risk of adverse effects.[70][71][72][73] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimizing radiation exposure to uninvolved structures.

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

Patients should be assessed for suitability for radiation therapy (e.g., based on age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[33] Those deemed unsuitable for radiation therapy 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: favorable 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 favorable 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) can receive two additional cycles of ABVD followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.[60] [65][67]

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[40]

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 – radiation therapy (30 Gy) (if restaging PET/CT negative)

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

radiation therapy (30 Gy) (if restaging PET/CT negative)

Treatment recommended for SOME patients in selected patient group

If restaging PET/CT is negative (Deauville score 1 to 3) then 30 Gy radiation therapy can be given.[60][65][67] 

Involved-site radiation therapy (ISRT) is preferred to traditional involved-field radiation therapy (IFRT) due to its lower risk of adverse effects.[70][71][72][73] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimizing radiation exposure to uninvolved structures.

Acute adverse effects of radiation therapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop esophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiation therapy can cause nausea and/or diarrhea. Fatigue is common in all patients receiving radiation therapy. Possible long-term adverse effects of radiation therapy 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: favorable disease and intended for combined-modality therapy
|
interim PET/CT positive (Deauville score 4)
Consider – 

biopsy (if restaging PET/CT positive)

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).[33]

Plus – biopsy

Back
ACUTE
|
early (stage I to II) classical HL: favorable 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).[33] 

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

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

Back
ACUTE
|
early (stage I to II) classical HL: favorable 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 minimizing risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favorable or unfavorable early-stage disease. German Hodgkin Study Group (GHSG) favorable 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/h if B symptoms are present; involvement of ≤2 nodal sites; and no extranodal disease; see Diagnostic criteria).[44][50]

Patients with favorable 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.[33]

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[40]

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.[5][33][54][65][66][74][75]

The most effective treatment for early-stage disease is combined-modality therapy, which comprises combination chemotherapy (e.g., ABVD) followed by radiation therapy.[51][52][53][54][55][56][57][58][59][60][61]

A chemotherapy-alone approach may be considered if avoiding radiation therapy is preferred (e.g., due to patient age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[33][62][63][64][65][66] The decision to omit radiation therapy 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 tumor control and higher rate of relapse compared with combined-modality therapy, but survival rates are similar.[51][52][53][58][60][64][66][67][68][69] [ Cochrane Clinical Answers logo ]

HL in older patients (ages >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[46][47][48]​​ 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.[49]

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – ABVD (2 cycles)

Back
ACUTE
|
early (stage I to II) classical HL: favorable disease and intended for chemotherapy alone
|
interim PET/CT negative (Deauville score 1 or 2)
Plus – 

ABVD (2 cycles)

Treatment recommended for ALL patients in selected patient group

Patients with favorable early-stage disease who are intended for chemotherapy alone and have a Deauville score of 1 or 2 on interim PET/CT (after two initial cycles of ABVD) can receive two additional cycles of ABVD.[60][64][66][67]

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: favorable disease and intended for chemotherapy alone
|
interim PET/CT negative (Deauville score 3)
Plus – 

ABVD (2 cycles) or AVD (4 cycles)

Treatment recommended for ALL patients in selected patient group

Patients with favorable early-stage disease who are intended for chemotherapy alone and have a Deauville score of 3 on interim PET/CT (after two initial cycles of ABVD) can receive two additional cycles of ABVD or four additional cycles of AVD (doxorubicin, vinblastine, dacarbazine).[60][64][66][67][68]

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: favorable 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 favorable 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) can receive two additional cycles of ABVD followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.[60][64][66][67]

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[40]

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 – radiation therapy (30 Gy) (if restaging PET/CT negative)

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

radiation therapy (30 Gy) (if restaging PET/CT negative)

Treatment recommended for SOME patients in selected patient group

If restaging PET/CT is negative (Deauville score 1 to 3) then 30 Gy radiation therapy should be considered.[60][65][67]

Involved-site radiation therapy (ISRT) is preferred to traditional involved-field radiation therapy (IFRT) due to its lower risk of adverse effects.[70][71][72][73]​ ISRT focuses radiation only on involved lymph nodes and nearby sites, minimizing radiation exposure to uninvolved structures.

Acute adverse effects of radiation therapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop esophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiation therapy can cause nausea and/or diarrhea. Fatigue is common in all patients receiving radiation therapy. Possible long-term adverse effects of radiation therapy 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: favorable disease and intended for chemotherapy alone
|
interim PET/CT positive (Deauville score 4)
Consider – 

biopsy (if restaging PET/CT positive)

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).[33]

Plus – biopsy

Back
ACUTE
|
early (stage I to II) classical HL: favorable 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).[33] 

early (stage I to II) classical HL: unfavorable 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: unfavorable 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 minimizing risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favorable or unfavorable early-stage disease. German Hodgkin Study Group (GHSG) favorable 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).[44][50]

Patients with unfavorable 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.[40]

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.[5][33][54]​​​[65][66][74][75]

The most effective treatment for early-stage disease is combined-modality therapy, which comprises combination chemotherapy (e.g., ABVD) followed by radiation therapy.[51][52][53][54][55][56][57][58][59][60][61]

A chemotherapy-alone approach may be considered if avoiding radiation therapy is preferred (e.g., due to patient age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[33][62][63][64][65][66]​ The decision to omit radiation therapy 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 tumor control and higher rate of relapse compared with combined-modality therapy, but survival rates are similar.[51][52][53][58][60][64][66][67][68][69] [ Cochrane Clinical Answers logo ]

HL in older patients (ages >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[46][47][48]​​ 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.[49]

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – ABVD (2 cycles) + radiation therapy (30 Gy)

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

ABVD (2 cycles) + radiation therapy (30 Gy)

Treatment recommended for ALL patients in selected patient group

Patients with unfavorable 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) can receive two additional cycles of ABVD followed by 30 Gy radiation therapy.[54][60][67]

Involved-site radiation therapy (ISRT) is preferred to traditional involved-field radiation therapy (IFRT) due to its lower risk of adverse effects.[70][71][72][73]​ ISRT focuses radiation only on involved lymph nodes and nearby sites, minimizing radiation exposure to uninvolved structures.

Acute adverse effects of radiation therapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop esophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiation therapy can cause nausea and/or diarrhea. Fatigue is common in all patients receiving radiation therapy. Possible long-term adverse effects of radiation therapy 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 escalated BEACOPP (2 cycles) + restaging PET/CT

Back
ACUTE
|
early (stage I to II) classical HL: unfavorable 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 escalated BEACOPP (2 cycles) + restaging PET/CT

Treatment recommended for ALL patients in selected patient group

Patients with unfavorable 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) can receive two additional cycles of ABVD or escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone), followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.[54][60][67]

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[40]

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

BEACOPP

bleomycin

and

etoposide

and

doxorubicin

and

cyclophosphamide

and

vincristine

and

procarbazine

and

prednisone

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

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

radiation therapy (30 Gy) (if restaging PET/CT negative)

Treatment recommended for SOME patients in selected patient group

If restaging PET/CT is negative (Deauville score 1 to 3) then 30 Gy radiation therapy can be given.[54][60][67]

Involved-site radiation therapy (ISRT) is preferred to traditional involved-field radiation therapy (IFRT) due to its lower risk of adverse effects.[70][71][72][73] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimizing radiation exposure to uninvolved structures.

Acute adverse effects of radiation therapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop esophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiation therapy can cause nausea and/or diarrhea. Fatigue is common in all patients receiving radiation therapy. Possible long-term adverse effects of radiation therapy 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: unfavorable disease (non-bulky or bulky) and intended for combined-modality therapy
|
interim PET/CT positive (Deauville score 4 or 5)
Consider – 

biopsy (if restaging PET/CT positive)

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).[33]

early (stage I to II) classical HL: unfavorable 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: unfavorable 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 minimizing risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favorable or unfavorable early-stage disease. German Hodgkin Study Group (GHSG) favorable 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).[44][50]

Patients with unfavorable 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.[40]

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.[5][33][54]​​​[65][66][74][75]

The most effective treatment for early-stage disease is combined-modality therapy, which comprises combination chemotherapy (e.g., ABVD) followed by radiation therapy.[51][52][53][54][55][56][57][58][59][60][61]​ 

A chemotherapy-alone approach may be considered if avoiding radiation therapy is preferred (e.g., due to patient age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[33][62][63][64][65][66]​ The decision to omit radiation therapy 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 tumor control and higher rate of relapse compared with combined-modality therapy, but survival rates are similar.[51][52][53][58][60][64][66][67][68][69] [ Cochrane Clinical Answers logo ]

HL in older patients (ages >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[46][47][48]​​ 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.[49]

See local specialist protocol for dosing guidelines.

Primary options

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – ABVD (2 cycles)

Back
ACUTE
|
early (stage I to II) classical HL: unfavorable disease (non-bulky) and intended for chemotherapy alone
|
interim PET/CT negative (Deauville score 1 to 2)
Plus – 

ABVD (2 cycles)

Treatment recommended for ALL patients in selected patient group

Patients with unfavorable early-stage disease (non-bulky) who are intended for chemotherapy alone and have a Deauville score of 1 or 2 on interim PET/CT (after two initial cycles of ABVD) can receive two additional cycles of ABVD.[60][64][66][67] 

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: unfavorable disease (non-bulky) and intended for chemotherapy alone
|
interim PET/CT negative (Deauville score 3)
Plus – 

ABVD (2 cycles) or AVD (4 cycles)

Treatment recommended for ALL patients in selected patient group

Patients with unfavorable early-stage disease (non-bulky) who are intended for chemotherapy alone and have a Deauville score of 3 on interim PET/CT (after two initial cycles of ABVD) can receive two additional cycles of ABVD or four additional cycles of AVD (doxorubicin, vinblastine, dacarbazine).[68]

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: unfavorable disease (non-bulky) 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 unfavorable 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) can receive two additional cycles of ABVD followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.[60][64][66][67] 

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[40]

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 – AVD (2 cycles) + radiation therapy (30 Gy) (if restaging PET/CT negative)

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

AVD (2 cycles) + radiation therapy (30 Gy) (if restaging PET/CT negative)

Treatment recommended for SOME patients in selected patient group

If restaging PET/CT is negative (Deauville score 1 to 3) then two additional cycles of AVD (doxorubicin, vinblastine, dacarbazine) followed by 30 Gy radiation therapy should be considered.[60][65][67]

Involved-site radiation therapy (ISRT) is preferred to traditional involved-field radiation therapy (IFRT) due to its lower risk of adverse effects.[70][71][72][73] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimizing radiation exposure to uninvolved structures.

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

See local specialist protocol for dosing guidelines.

Primary options

AVD

doxorubicin

and

vinblastine

and

dacarbazine

Consider – biopsy (if restaging PET/CT positive)

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

biopsy (if restaging PET/CT positive)

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).[33] 

Plus – biopsy

Back
ACUTE
|
early (stage I to II) classical HL: unfavorable disease (non-bulky) 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).[33] 

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

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

Back
ACUTE
|
early (stage I to II) classical HL: unfavorable 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 minimizing risk of toxicity and long-term complications.

The absence or presence of specific prognostic criteria determines whether the patient has favorable or unfavorable early-stage disease. German Hodgkin Study Group (GHSG) favorable 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).[44][50]

Patients with unfavorable 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.[40]

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.[5][33][54]​​​[65][66][74][75]

The most effective treatment for early-stage disease is combined-modality therapy, which comprises combination chemotherapy (e.g., ABVD) followed by radiation therapy.[51][52][53][54][55][56][57][58][59][60][61]​ 

A chemotherapy-alone approach may be considered if avoiding radiation therapy is preferred (e.g., due to patient age, sex, family history of cancer or cardiac disease, comorbidities, sites of involvement).[33][62][63][64][65][66]​ The decision to omit radiation therapy 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 tumor control and higher rate of relapse compared with combined-modality therapy, but survival rates are similar.[51][52][53][58][60][64][66][67][68][69] [ Cochrane Clinical Answers logo ] ​ 

HL in older patients (ages >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[46][47][48]​​ 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.[49]

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: unfavorable 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 unfavorable 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) can receive four additional cycles of AVD (doxorubicin, vinblastine, dacarbazine).[68]

See local specialist protocol for dosing guidelines.

Primary options

AVD

doxorubicin

and

vinblastine

and

dacarbazine

Plus – escalated BEACOPP (2 cycles) + restaging PET/CT

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

escalated BEACOPP (2 cycles) + restaging PET/CT

Treatment recommended for ALL patients in selected patient group

Patients with unfavorable 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) can receive two additional cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.[54][60][68][76][77]

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[40]

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

BEACOPP

bleomycin

and

etoposide

and

doxorubicin

and

cyclophosphamide

and

vincristine

and

procarbazine

and

prednisone

Consider – escalated BEACOPP (2 cycles) (if restaging PET/CT negative)

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

escalated BEACOPP (2 cycles) (if restaging PET/CT negative)

Treatment recommended for SOME patients in selected patient group

If restaging PET/CT is negative (Deauville score 1 to 3) then two additional cycles of escalated BEACOPP can be given.[54][60][68][76][77]

See local specialist protocol for dosing guidelines.

Primary options

BEACOPP

bleomycin

and

etoposide

and

doxorubicin

and

cyclophosphamide

and

vincristine

and

procarbazine

and

prednisone

Consider – biopsy (if restaging PET/CT positive)

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

biopsy (if restaging PET/CT positive)

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).[33]

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 minimizing risk of toxicity and long-term complications.

ABVD is a preferred initial treatment for patients with advanced-stage disease.[33][68]

A PET-adapted treatment approach can be used in patients with advanced-stage disease to guide treatment decisions regarding escalation or de-escalation of chemotherapy.[68][94][95][96]

Patients with advanced-stage disease who are intended for standard induction therapy with ABVD chemotherapy typically receive two initial cycles of ABVD, followed by an interim PET/CT scan to assess metabolic response and inform subsequent treatment.[68]

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[40]

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 (ages >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[46][47][48]​​ 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.[49]

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) can receive four additional cycles of AVD (doxorubicin, vinblastine, dacarbazine).[33][68]

See local specialist protocol for dosing guidelines.

Primary options

AVD

doxorubicin

and

vinblastine

and

dacarbazine

Plus – escalated BEACOPP (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): age ≤60 years
Plus – 

escalated BEACOPP (3 cycles) + restaging PET/CT

Treatment recommended for ALL patients in selected patient group

Patients with advanced-stage disease who are aged ≤60 years and have a Deauville score of 4 or 5 on interim PET/CT (after two initial cycles of ABVD) can receive three additional cycles of escalated BEACOPP, followed by a restaging PET/CT scan to assess metabolic response and inform subsequent treatment.[68] 

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[40]

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).

See local specialist protocol for dosing guidelines.

Primary options

BEACOPP

bleomycin

and

etoposide

and

doxorubicin

and

cyclophosphamide

and

vincristine

and

procarbazine

and

prednisone

Consider – escalated BEACOPP (1 cycle) ± radiation therapy (if restaging PET/CT negative)

Back
ACUTE
|
advanced (stage III to IV) classical HL: intended for standard induction therapy (chemotherapy)
|
interim PET/CT positive (Deauville score 4 or 5): age ≤60 years
Consider – 

escalated BEACOPP (1 cycle) ± radiation therapy (if restaging PET/CT negative)

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 escalated BEACOPP can be given.[68]

Consolidation radiation therapy (i.e., after initial chemotherapy) can be avoided in patients with advanced-stage disease if end-of-treatment PET/CT is negative.[76][82][97][98][99][100][101][102] 

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

Involved-site radiation therapy (ISRT) is preferred to traditional involved-field radiation therapy (IFRT) due to its lower risk of adverse effects.[70][71][72][73] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimizing radiation exposure to uninvolved structures.

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

See local specialist protocol for dosing guidelines.

Primary options

BEACOPP

bleomycin

and

etoposide

and

doxorubicin

and

cyclophosphamide

and

vincristine

and

procarbazine

and

prednisone

Consider – biopsy (if restaging PET/CT positive)

Back
ACUTE
|
advanced (stage III to IV) classical HL: intended for standard induction therapy (chemotherapy)
|
interim PET/CT positive (Deauville score 4 or 5): age ≤60 years
Consider – 

biopsy (if restaging PET/CT positive)

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).[33] 

Plus – individualized treatment

Back
ACUTE
|
advanced (stage III to IV) classical HL: intended for standard induction therapy (chemotherapy)
|
interim PET/CT positive (Deauville score 4 or 5): age >60 years
Plus – 

individualized treatment

Treatment recommended for ALL patients in selected patient group

Patients with advanced-stage disease ages >60 years who have a Deauville score of 4 or 5 on interim PET/CT (after two initial cycles of ABVD) are recommended individualized treatment to minimize toxicity while maintaining efficacy.[5][33]

Bleomycin should be used with caution; standard regimens may be adapted to remove bleomycin or restrict its use to only two cycles.[5][33]

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

1st line – brentuximab vedotin + AVD

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

brentuximab vedotin + AVD

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

Brentuximab vedotin plus AVD (doxorubicin, vinblastine, dacarbazine) is a preferred initial treatment for patients with advanced-stage disease.[33][68]

Brentuximab vedotin plus AVD offers a survival advantage compared with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in patients with advanced-stage disease.[33][86][87][88]​ However, caution is required when used in older patients (age >60 years) and in those with baseline neuropathy.

HL in older patients (ages >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[46][47][48]​​ 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.[49]

For older patients, sequential brentuximab vedotin plus AVD may be a preferred option.[84] This involves administeriing 2 cycles of brentuximab vedotin followed by 6 cycles of AVD followed by 4 cycles of brentuximab vedotin.[84]

See local specialist protocol for dosing guidelines.

Primary options

brentuximab vedotin

and

doxorubicin

and

vinblastine

and

dacarbazine

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

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

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

escalated BEACOPP (2 cycles) + interim PET/CT

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

A PET-adapted treatment approach can be used in patients with advanced-stage disease to guide treatment decisions regarding escalation or de-escalation of chemotherapy.[68][94][95][96]

Selected patients with advanced-stage disease (e.g., those with an International Prognostic Score [IPS] ≥4 and age <60 years) may be suitable for upfront intensive induction chemotherapy comprising two initial cycles of escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone), followed by an interim PET/CT scan to assess metabolic response and inform subsequent treatment.[94][95]

Metabolic response is determined using the Deauville criteria, which assigns a score of 1 to 5 based on fluorodeoxyglucose (FDG) uptake at involved sites.[40]

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 (ages >60 years) is associated with poorer outcomes and higher treatment-related toxicity and mortality compared with younger patients.[46][47][48]​​ 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.[49]

See local specialist protocol for dosing guidelines.

Primary options

BEACOPP

bleomycin

and

etoposide

and

doxorubicin

and

cyclophosphamide

and

vincristine

and

procarbazine

and

prednisone

Plus – escalated BEACOPP (2 cycles) or ABVD (4 cycles)

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

escalated BEACOPP (2 cycles) or ABVD (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 escalated BEACOPP) can receive two additional cycles of escalated BEACOPP or four additional cycles of ABVD.[33][94][95][96]

Bleomycin may be omitted from ABVD to reduce toxicity.

See local specialist protocol for dosing guidelines.

Primary options

BEACOPP

bleomycin

and

etoposide

and

doxorubicin

and

cyclophosphamide

and

vincristine

and

procarbazine

and

prednisone

OR

ABVD

doxorubicin

and

bleomycin

and

vinblastine

and

dacarbazine

Plus – biopsy or treatment escalation

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 or treatment escalation

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 escalated BEACOPP) are recommended a biopsy to inform subsequent treatment (e.g., salvage therapy or treatment escalation).[33] 

Patients with a positive biopsy may require salvage therapy.

Patients with a negative biopsy can receive two additional cycles of escalated BEACOPP followed by a restaging PET/CT scan.[94][95][96] If restaging PET/CT is negative (Deauville score 1 to 3) then two additional cycles of escalated BEACOPP can be given.[33][94][95][96] If restaging PET/CT is positive (Deauville score 4 or 5) then another biopsy is recommended.[33]

Consolidation radiation therapy (i.e., after initial chemotherapy) can be avoided in patients with advanced-stage disease if end-of-treatment PET/CT is negative.[76][82][97][98][99][100][101][102] 

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

Involved-site radiation therapy (ISRT) is preferred to traditional involved-field radiation therapy (IFRT) due to its lower risk of adverse effects.[70][71][72][73] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimizing radiation exposure to uninvolved structures.

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

See local specialist protocol for dosing guidelines.

Primary options

BEACOPP

bleomycin

and

etoposide

and

doxorubicin

and

cyclophosphamide

and

vincristine

and

procarbazine

and

prednisone

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

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

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

radiation therapy (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 minimizing risk of late effects. Overall prognosis for patients with early-stage NLPHL is excellent.

Radiation therapy alone at a dose 30 to 36 Gy is recommended for most patients with asymptomatic early (stage IA and IIA) non-bulky NLPHL.[33][70][130]

Involved-site radiation therapy (ISRT) is the preferred approach (although most available data are for involved-field radiation therapy [IFRT]).[70]

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

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

Retrospective studies have reported excellent remission and survival outcomes with radiation therapy alone for early-stage NLPHL.[131][132][133][134] Randomized 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 radiation therapy.[135] Observation is also an option for selected patients with stage IA non-bulky disease who have a completely excised solitary lymph node.[33]

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

1st line – rituximab + chemotherapy + radiation therapy; or observation (if asymptomatic)

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

rituximab + chemotherapy + radiation therapy; or observation (if asymptomatic)

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 minimizing 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, prednisone], or R-CVbP [rituximab, cyclophosphamide, vinblastine, prednisone]) followed by radiation therapy (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).[33][130][136]​​

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 radiation therapy (ISRT) is preferred to traditional involved-field radiation therapy (IFRT) due to its lower risk of adverse effects.[70][71][72][73] ISRT focuses radiation only on involved lymph nodes and nearby sites, minimizing radiation exposure to uninvolved structures.

Acute adverse effects of radiation therapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop esophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiation therapy can cause nausea and/or diarrhea. Fatigue is common in all patients receiving radiation therapy. Possible long-term adverse effects of radiation therapy 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 radiation therapy.[135]

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

prednisone

OR

R-CVbP

rituximab

and

cyclophosphamide

and

vinblastine

and

prednisone

advanced (stage III to IV) NLPHL

1st line – observation or rituximab + chemotherapy (± radiation therapy)

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

observation or rituximab + chemotherapy (± radiation therapy)

Observation may be appropriate for patients with asymptomatic advanced-stage disease.[33][130]

Systemic treatment with rituximab plus combination chemotherapy (e.g., R-ABVD [rituximab, doxorubicin, bleomycin, vinblastine, dacarbazine], R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone], or R-CVbP [rituximab, cyclophosphamide, vinblastine, prednisone]) with or without radiation therapy is recommended for patients with symptomatic advanced-stage disease or rapid progression.[33][137][138]

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 radiation therapy (ISRT) is preferred to traditional involved-field radiation therapy (IFRT) due to its lower risk of adverse effects.[70][71][72][73]​ ISRT focuses radiation only on involved lymph nodes and nearby sites, minimizing radiation exposure to uninvolved structures.

Acute adverse effects of radiation therapy depend on the region treated and the dose employed. Patients receiving treatment to the mediastinum can develop esophagitis, clinically apparent as odynophagia that sometimes requires opioid analgesics to maintain oral intake. Infradiaphragmatic radiation therapy can cause nausea and/or diarrhea. Fatigue is common in all patients receiving radiation therapy. Possible long-term adverse effects of radiation therapy 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

prednisone

OR

R-CVbP

rituximab

and

cyclophosphamide

and

vinblastine

and

prednisone

ONGOING

refractory or relapsed classical HL

1st line – salvage therapy (combination chemotherapy) + PET/CT

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

salvage therapy (combination chemotherapy) + PET/CT

Refractory or relapsed HL should be confirmed with biopsy.

Treatment for refractory or relapsed HL must be individualized, 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.

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.[33][103][104][105][106][107] 

The role of salvage therapy is to reduce tumor burden and mobilize stem cells before conditioning and ASCT.[5]

Combination chemotherapy regimens can be used for salvage therapy. The optimal salvage regimen is unclear due to the lack of head-to-head randomized trials; however, the following are commonly used: BeGEV (bendamustine, gemcitabine, vinorelbine); DHAP (dexamethasone, cytarabine, cisplatin); GVD (gemcitabine, vinorelbine, pegylated liposomal doxorubicin); ICE (ifosfamide, carboplatin, etoposide); IGEV (ifosfamide, gemcitabine, vinorelbine).[106][107][113][114][115][116][117][140]

A PET-adapted treatment approach is used for refractory or relapsed HL in order to optimize 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.[123][124]​ 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.[125][126][127]

See local specialist protocol for dosing guidelines.

Primary options

BeGEV

bendamustine

and

gemcitabine

and

vinorelbine

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)

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).[103][104][105][106][107]

Radiation therapy 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, but this is controversial.[109][110]​ In selected patients, radiation therapy alone or chemotherapy alone is appropriate following salvage therapy.[111][112]

Consider – brentuximab vedotin (maintenance)

Back
ONGOING
|
refractory or relapsed classical HL
Consider – 

brentuximab vedotin (maintenance)

Treatment recommended for SOME patients in selected patient group

Brentuximab vedotin (an anti-CD30 monoclonal antibody conjugated to monomethyl auristatin E) is approved for use as consolidation/maintenance therapy following ASCT in patients at high risk for relapse (e.g., those refractory to initial treatment; those who relapse within 12 months following initial treatment with ABVD or escalated BEACOPP; or those with extranodal disease).[141][128][129]

Maintenance brentuximab vedotin is recommended for 16 cycles (as per the AETHERA trial) or until unacceptable toxicity or relapse (whichever occurs first).[128]

It is not recommended in patients with prior evidence of disease refractory to brentuximab vedotin.[128] However, it may be considered for patients previously treated with brentuximab vedotin if durable remission (at least 12 months) was achieved before relapse.

See local specialist protocol for dosing guidelines.

Primary options

brentuximab vedotin

2nd line – salvage therapy (immunotherapy regimens)

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ONGOING
|
refractory or relapsed classical HL
2nd line – 

salvage therapy (immunotherapy regimens)

Several immunotherapeutic agents are available for patients with relapsed or refractory classical HL.

The following immunotherapy-based combination regimens may be considered for use as salvage therapy before ASCT (in those who have not previously undergone ASCT) in the refractory or relapsed setting: brentuximab vedotin plus bendamustine; brentuximab vedotin plus nivolumab; brentuximab vedotin plus ICE (ifosfamide, carboplatin, etoposide); nivolumab plus ICE; or pembrolizumab plus GVD (gemcitabine, vinorelbine, pegylated liposomal doxorubicin).[118][119][120][121][122]

See local specialist protocol for dosing guidelines.

Primary options

brentuximab vedotin

OR

brentuximab vedotin

and

bendamustine

OR

brentuximab vedotin

and

nivolumab

OR

brentuximab vedotin

and

ifosfamide

and

carboplatin

and

etoposide

OR

pembrolizumab

OR

pembrolizumab

and

gemcitabine

and

vinorelbine

and

doxorubicin liposomal

OR

nivolumab

OR

nivolumab

and

ifosfamide

and

carboplatin

and

etoposide

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)

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).[103][104][105][106][107]

Radiation therapy 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, but this is controversial.[109][110]​ In selected patients, radiation therapy alone or chemotherapy alone is appropriate following salvage therapy.[111][112]

Consider – brentuximab vedotin (maintenance)

Back
ONGOING
|
refractory or relapsed classical HL
Consider – 

brentuximab vedotin (maintenance)

Treatment recommended for SOME patients in selected patient group

Brentuximab vedotin (an anti-CD30 monoclonal antibody conjugated to monomethyl auristatin E) is approved for use as consolidation/maintenance therapy following ASCT in patients at high risk for relapse (e.g., those refractory to initial treatment; those who relapse within 12 months following initial treatment with ABVD or escalated BEACOPP; or those with extranodal disease).[141][128][129]

Maintenance brentuximab vedotin is recommended for 16 cycles (as per the AETHERA trial) or until unacceptable toxicity or relapse (whichever occurs first).[128]

It is not recommended in patients with prior evidence of disease refractory to brentuximab vedotin.[128] However, it may be considered for patients previously treated with brentuximab vedotin if durable remission (at least 12 months) was achieved before relapse.

See local specialist protocol for dosing guidelines.

Primary options

brentuximab vedotin

refractory or relapsed NLPHL

1st line – salvage therapy or observation

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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 lymphoma.

Treatment for refractory or relapsed NLPHL must be individualized, taking into consideration factors such as previous first-line treatment (e.g., R-ABVD [rituximab, doxorubicin, bleomycin, vinblastine, dacarbazine] with radiation therapy), patient age, medical comorbidities, duration of first remission, and stage at relapse.[130]

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.[33] 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, prednisone); R-CVbP (rituximab, cyclophosphamide, vinblastine, prednisone); rituximab plus bendamustine; R-DHAP (rituximab, dexamethasone, cytarabine, cisplatin); R-ICE (rituximab, ifosfamide, carboplatin, etoposide); or R-IGEV (rituximab, ifosfamide, gemcitabine, vinorelbine).

Rituximab alone can be considered for patients who relapse with limited stage disease and low tumor volume.[33][139] 

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