Version July 2025
INTRODUCTION —
Classic Hodgkin lymphoma (cHL) refers to lymphomas in which malignant Hodgkin/Reed-Sternberg (HRS) cells are embedded in a polymorphous infiltrate of reactive (ie, nonmalignant) lymphocytes, eosinophils, fibroblasts, and other inflammatory cell types (picture 1). Prototypical HRS cells have a characteristic morphology with prominent nucleoli in separate nuclear lobes ("owl's eyes"), but mononuclear and other HRS variants are common. HRS cells are derived from transformed B lymphocytes.
The four histologic subtypes of cHL (nodular sclerosis cHL, lymphocyte-rich cHL, mixed cellularity cHL, and lymphocyte-depleted cHL) are associated with different demographic features and prognosis, but the cHL subtype does not influence treatment.
The treatment of cHL is stratified by disease stage:
●Advanced stage – Stage III or stage IV
Some studies have included patients with stage II with an unfavorable prognosis in trials of advanced-stage cHL.
●Limited stage – Stage I or stage II; the management of limited-stage cHL is further stratified according to the presence of adverse prognostic features.
The treatment of advanced-stage cHL is discussed in this topic.
Related topics include:
●(See "Classic Hodgkin lymphoma: Presentation, evaluation, and diagnosis in adults".)
●(See "Pretreatment evaluation, staging, and treatment stratification of classic Hodgkin lymphoma".)
●(See "Treatment of favorable prognosis early (stage I-II) classic Hodgkin lymphoma".)
PRETREATMENT EVALUATION —
Pretreatment evaluation of a patient with cHL establishes the stage (ie, extent and sites of disease), medical comorbidities, performance status (table 1), and medical fitness.
Clinical and laboratory studies
●History – Constitutional "B" symptoms (unexplained fever >38°C, drenching night sweats, weight loss >10 percent), location and duration of lymphadenopathy and/or organomegaly, and comorbid illnesses.
●Examination – A physical examination may reveal lymphadenopathy and findings associated with comorbid conditions (eg, heart or lung disease).
●Laboratory
•Hematology
-Complete blood count and differential count
-Erythrocyte sedimentation rate (ESR)
•Chemistries – Complete metabolic panel, including kidney and liver function tests, and lactate dehydrogenase.
•Infectious – Human immunodeficiency virus (HIV), hepatitis B, hepatitis C.
Imaging
●Positron emission tomography (PET)/computed tomography (CT)
●Other – Contrast-enhanced CT and/or magnetic resonance imaging (MRI), if needed, to evaluate suspected extranodal sites of disease.
Other
●Heart – Echocardiogram or radionuclide ventriculography for cardiac ejection fraction.
Some clinicians prescribe a statin to reduce the risk of cardiac dysfunction in patients who will receive an anthracycline. A phase 3 trial that randomly assigned atorvastatin versus placebo to 300 patients who were scheduled to receive anthracycline-based chemotherapy demonstrated less decline in ejection fraction among those who received atorvastatin [1], as discussed separately. (See "Risk and prevention of anthracycline cardiotoxicity", section on 'Primary prevention with cardiovascular drugs'.)
●Bone marrow examination – Not generally required unless it is needed to evaluate unexplained thrombocytopenia and/or neutropenia.
●Fertility
•Pregnancy test, if appropriate
•Fertility preservation, if appropriate
Disease stage — Disease stage is based on Lugano criteria (table 2) using clinical evaluation and PET/CT.
Prognosis — The International Prognostic Score (IPS) is used to estimate prognosis in patients with advanced-stage cHL prior to treatment.
The IPS (table 3) (calculator 1) incorporates seven factors (ie, serum albumin, hemoglobin, sex, age, stage, white blood cell count, and absolute lymphocyte count) to define six prognostic groups with distinct outcomes. IPS criteria, categories, and outcomes are discussed in detail separately. (See "Pretreatment evaluation, staging, and treatment stratification of classic Hodgkin lymphoma", section on 'International Prognostic Score (IPS)'.)
The Advanced-Stage Hodgkin lymphoma International Prognostic Index (A-HIPI) can also be used to estimate survival [2]. This model was developed using multivariable analysis of data from 4027 patients treated in eight studies of advanced-stage cHL and was validated with 1431 patients from prospective studies and tumor registries.
INITIAL TREATMENT
Nivolumab plus AVD (preferred) — For initial treatment of advanced-stage cHL, we suggest N+AVD (nivolumab plus doxorubicin, vinblastine, dacarbazine) rather than BV+AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine), based on a more favorable balance of outcomes and toxicity.
N+AVD achieved better outcomes with less toxicity than BV+AVD in a phase 3 trial (S1826) of patients with advanced-stage cHL [3]. Previously, BV+AVD was shown to be superior to ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) in the ECHELON-1 trial [4].
N+AVD is contraindicated in patients with rheumatoid arthritis, inflammatory bowel disease, and other autoimmune illnesses that require immunosuppressive therapy. Alternative regimens, for when nivolumab is not available or is contraindicated, are discussed below. (See 'Alternatives' below.)
Some experts offer BrECADD (BV, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) to selected fit patients ≤60 years who have advanced-stage cHL with adverse prognostic features, based on results from the HD21 trial [5]. No studies have directly compared BrECADD with N+AVD, and it is difficult to compare the S1826 and HD21 trials because of different inclusion criteria, endpoints, and toxicity profiles. Administration, toxicity, and outcomes with BrECADD are presented below. (See 'BrECADD' below.)
●Administration – N+AVD is suitable for adults of all ages, but it is contraindicated in patients with autoimmune conditions that require immunosuppressive therapy.
Treat with the following on days 1 and 15 of each 28-day cycle for six cycles:
•Nivolumab 240 mg in adults or 3 mg/kg in children 12 to <18 years.
•Doxorubicin 25 mg/m2
•Vinblastine 6 mg/m2
•Dacarbazine 375 mg/m2
Treatment with filgrastim (G-CSF) is optional for patients receiving N+AVD.
For older patients and/or those with cardiac comorbidities, dexrazoxane can be considered to reduce the risk of heart failure, as discussed separately. (See "Risk and prevention of anthracycline cardiotoxicity".)
●Toxicity – Neutropenia is common, but infections and sepsis are uncommon adverse effects (AEs).
Immune-related AEs are uncommon in patients without an autoimmune condition, but thyroid dysfunction and rare cases of severe immune-mediated toxicity may occur. (See "Overview of toxicities associated with immune checkpoint inhibitors".)
●Outcomes – N+AVD achieved better outcomes with a more favorable toxicity profile than BV+AVD in the S1826 trial of advanced-stage cHL [3].
Treatment in S1826 was randomly assigned to 970 patients (≥12 years) with newly diagnosed stage III or IV cHL; approximately one-third of patients had International Prognostic Score (IPS) ≥4 and/or a large mediastinal mass [3]. G-CSF was mandatory with BV+AVD and optional with N+AVD (it was given to approximately one-half of patients), dexrazoxane was optional (it was given to one-quarter of patients with both treatments), and consolidative radiation therapy (RT; 30 gray [Gy]) was allowed for persistent positron emission tomography (PET)-positive disease at the end of treatment (it was given to only 7 of 970 patients). N+AVD achieved superior two-year progression-free survival (PFS; 92 versus 83 percent) and disease progression or death (hazard ratio [HR] 0.45 [95% CI 0.30-0.65]). Two-year overall survival (OS) was 99 percent with N+AVD and 98 percent with BV+AVD. Febrile neutropenia, sepsis, and infections were comparable between groups. Fewer patients receiving N+AVD required discontinuation of nivolumab compared with discontinuation of BV in patients receiving BV+AVD (9 versus 22 percent).
Subgroup analysis of 95 patients >60 years in S1826 reported less two-year disease progression or death with N+AVD than BV+AVD (14.6 versus 36.2 percent; HR 0.30 [95% CI 0.12-0.72]) [3]. Nearly all AEs except neutropenia occurred more frequently with BV+AVD; grade ≥3 neutropenia was reported in 48 percent of patients treated with N+AVD and in 26 percent with BV+AVD. Febrile neutropenia, sepsis, and infections were more common in older patients than in patients 18 to 60 years (33 versus 20 percent), but they were comparable in both treatment arms.
Alternatives — When nivolumab is contraindicated or not available, the preferred initial treatment varies by age and comorbidities.
As discussed above, N+AVD is contraindicated in patients with rheumatoid arthritis, inflammatory bowel disease, and other autoimmune illnesses that require immunosuppressive therapy. (See 'Nivolumab plus AVD (preferred)' above.)
≤60 years — When N+AVD is not suitable/available for patients ≤60 years, we generally treat with BV+AVD.
●BV+AVD – BV+AVD is contraindicated in patients with moderate pre-existing peripheral neuropathy, and its use is generally limited to patients ≤60 years.
BV+AVD was superior to ABVD in the ECHELON-1 trial of advanced-stage cHL, in which patients were randomly assigned to six cycles of either ABVD or BV+AVD [4].
Administration, toxicity, and outcomes with BV+AVD are discussed below. (See 'BV+AVD' below.)
When neither nivolumab nor BV is suitable/available, we consider the RATHL protocol and BrECADD acceptable. No studies have directly compared N+AVD or BV+AVD with either RATHL or BrECADD nor directly compared RATHL versus BrECADD.
●RATHL – In the RATHL trial, patients with a complete response (CR) after two cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) received four cycles of AVD (ie, bleomycin omitted) [6].
Administration, toxicity, and outcomes in RATHL trial are discussed separately. (See "Classic Hodgkin lymphoma (cHL): Treatment of unfavorable prognosis early (stage I-II) cHL in adults", section on 'Response-guided therapy'.)
●BrECADD – BrECADD is acceptable for fit patients ≤60 years with adverse prognostic features.
In the phase 3 HD21 trial in patients with advanced-stage cHL or other adverse prognostic features, BrECADD was superior to escalated BEACOPP (escBEACOPP; bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) [5].
Administration, toxicity, and outcomes with BrECADD, including a comparison of outcomes with N+AVD in the S1826 trial and BrECADD in the HD21 trial, are presented below. (See 'BrECADD' below.)
Dexrazoxane can be considered to reduce the risk of heart failure with anthracycline-based therapy, as discussed separately. (See "Risk and prevention of anthracycline cardiotoxicity".)
Management options for patients who are unlikely to tolerate any of the regimens described above are discussed below. (See 'Frail patients' below.)
>60 years — When N+AVD is not suitable/available for patients >60 years, we generally treat with sequential BV-AVD-BV.
As discussed above, N+AVD is contraindicated in patients with autoimmune illnesses that require immunosuppressive therapy. (See 'Nivolumab plus AVD (preferred)' above.)
Dexrazoxane can be considered to reduce the risk of heart failure with anthracycline-based therapy, as discussed separately. (See "Risk and prevention of anthracycline cardiotoxicity".)
Discussed below are management strategies for patients who are ineligible for anthracycline-based therapy. (See 'Frail patients' below.)
Sequential BV-AVD-BV involves a lead-in with single-agent BV to provide early disease control, followed by six cycles of AVD, and then four final cycles of consolidation with single-agent BV. The regimen minimizes neurotoxicity by sequential (rather than simultaneous) treatment with BV and AVD, and it reduces or delays relapses with four final cycles of BV consolidation therapy. Note that conventional BV+AVD (ie, simultaneous treatment with BV and AVD) is generally restricted to patients ≤60 years because of excessive toxicity in older patients.
●Administration
Sequential BV-AVD-BV comprises [7]:
•BV lead-in – BV 1.8 mg/kg on day 1 and day 22
Followed by:
•Six cycles of AVD (28-day cycles)
-Doxorubicin – 25 mg/m2 intravenous (IV) on days 1 and 15
-Vinblastine – 6 mg/m2 IV on days 1 and 15
-Dacarbazine – 375 mg/m2 IV on days 1 and 15
Followed by:
•BV consolidation – Four cycles of 1.8 mg/kg every three weeks
●Toxicity – Sequential BV-AVD-BV is associated with neutropenia, infections, and peripheral neuropathy.
●Outcomes – A phase 2 study reported outcomes with sequential BV-AVD-BV in 48 patients ≥60 years with cHL [7]. Most patients had advanced-stage disease (81 percent with stage III or IV), and 60 percent had an IPS score of 3 to 7. After two lead-in treatments with single-agent BV, the overall response rate (ORR) was 82 percent (including 36 percent CR), and ORR was 95 percent (including 90 percent CR) after six cycles of AVD in 42 evaluable patients. Patients then received four cycles of single-agent BV. Two-year OS was 93 percent, and two-year PFS was 84 percent, even though only 52 percent of patients completed all planned therapy. Grade ≥3 AEs were reported in 42 percent of patients; the most common grade ≥3 AEs were neutropenia, febrile neutropenia/pneumonia, and diarrhea. One-third of patients had grade 2 peripheral neuropathy, which was reversible in most patients.
MONITORING —
Positron emission tomography (PET) is used to document the response to treatment after completing planned chemotherapy.
Treatment response — Response is judged using the five-point (Deauville) scoring system (table 4) according to the Lugano classification (table 2):
●Complete response (CR) – PET score 1 to 3.
●Less than CR – PET score 4 to 5; consider biopsy to exclude an alternative diagnosis (eg, infection, another malignancy).
Evaluate and manage like refractory disease, as described separately. (See "Treatment of relapsed or refractory classic Hodgkin lymphoma".)
Surveillance — After completing planned therapy, the patient is monitored for relapse and adverse effects of treatment. Imaging should be limited to avoid unnecessary radiation exposure.
●Frequency of visits – The patient should be seen every three months in the first year, every four to six months in the second year, and then annually.
●Evaluation
•Clinical evaluation and screening laboratory studies. A complete blood count should be obtained annually to monitor for development of a therapy-related myeloid neoplasm.
•Imaging is generally performed only for suspected relapse.
If clinically indicated, CT can be obtained up to every six months for the first two years (ie, ≤4 CTs total) or if relapse is suspected. To reduce radiation exposure and avoid false-positive results, PET should be performed only for a suspected relapse.
TREATMENTS
N+AVD — N+AVD (nivolumab plus doxorubicin, vinblastine, dacarbazine) is suitable for treating adults of all ages, but it is contraindicated in patients with certain autoimmune illnesses.
Administration, contraindications, and outcomes with N+AVD are presented above. (See 'Nivolumab plus AVD (preferred)' above.)
BV+AVD — BV+AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) is generally limited to patients <60 years, and it is contraindicated in patients with pre-existing moderate peripheral neuropathy.
●Administration – Advanced-stage cHL is treated with six 28-day cycles of BV+AVD (table 5); treatment on days 1 and 15 constitutes one cycle.
•BV – 1.2 mg/kg intravenous (IV) on days 1 and 15
•Doxorubicin – 25 mg/m2 IV on days 1 and 15
•Vinblastine – 6 mg/m2 IV on days 1 and 15
•Dacarbazine – 375 mg/m2 IV on days 1 and 15
Filgrastim (G-CSF) must be given to lessen neutropenia and the risk of neutropenic fever [8].
BV is approved by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of advanced-stage cHL.
●Toxicity – BV+AVD is associated with peripheral neuropathy and cytopenias.
Peripheral neuropathy occurred in two-thirds of patients treated with BV+AVD in the ECHELON-1 trial, but this adverse effect (AE) improves or resolves in most patients. [4]. Febrile neutropenia occurred in 11 percent of patients treated with BV+AVD when G-CSF was administered [8].
●Outcomes – BV+AVD achieved superior survival for patients with advanced-stage cHL compared with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), but it was associated with cytopenias and peripheral neuropathy.
In the phase 3 ECHELON-1 trial, 1334 patients with advanced-stage cHL were randomly assigned to six cycles of either ABVD or BV+AVD [4]. Approximately 90 percent of patients in both trial arms received six cycles of therapy. Compared with ABVD, BV+AVD achieved superior six-year overall survival (OS; 93.9 versus 89.4 percent; hazard ratio [HR] for death 0.59 [95% CI 0.40-0.88]) and six-year progression-free survival (PFS; HR 0.68 [95% CI 0.53-0.86]). Subgroup analysis of ECHELON-1 did not report a survival advantage with BV+AVD compared with ABVD in patients >60 years.
In ECHELON-1, BV+AVD was associated with more grade ≥3 AEs (83 versus 66 percent), including more grade ≥3 neutropenia (58 versus 45 percent) and febrile neutropenia (19 versus 8 percent), but both AEs improved after prophylactic G-CSF was incorporated into the treatment protocol for BV+AVD [9]. There was more peripheral neuropathy with BV+AVD (67 percent any grade; 20 percent grade 2; 11 percent grade ≥3) compared with ABVD (43 percent any grade; 9 percent grade 2; 2 percent grade ≥3), but neuropathy improved over time. Among patients treated with BV+AVD, 11 percent had persistent grade 1 neuropathy, and 6 percent had persistent grade 2 neuropathy; corresponding rates after ABVD were 6 and 2 percent.
Additional comments about treatment with ABVD in the ECHELON-1 trial are presented below. (See 'ABVD' below.)
Sequential BV-AVD-BV — Sequential BV-AVD-BV comprises lead-in therapy with two treatments with single-agent BV, followed by six cycles of AVD, and followed by four cycles of single-agent BV consolidation. Sequential BV-AVD-BV is considerably less toxic than conventional BV+AVD (ie, simultaneous administration of BV and AVD).
Administration, toxicity, and outcomes with sequential BV-AVD-BV are discussed above. (See '>60 years' above.)
ABVD — ABVD is associated with substantial lung toxicity. We avoid bleomycin-containing regimens in patients >60 years.
The ECHELON-1 trial reported inferior results with ABVD compared with BV+AVD [4]. However, the interpretation of findings should recognize that treatment in that trial was not response-guided and that patients assigned to ABVD received six cycles of bleomycin-containing chemotherapy. (See 'BV+AVD' above.)
If ABVD is given, it should use the regimen from the RATHL trial, in which bleomycin was omitted from further treatments for patients who achieved a complete response by positron emission tomography (PET) after two cycles of ABVD [6]. Administration of ABVD and outcomes from the RATHL trial are discussed separately. (See "Classic Hodgkin lymphoma (cHL): Treatment of unfavorable prognosis early (stage I-II) cHL in adults".)
Conventional ABVD causes substantial toxicity in older patients. Treatment of 44 patients ≥60 years in the E2496 trial was associated with a 78 percent two-year OS and 66 percent two-year failure-free survival, but treatment-related mortality was 9 percent [10]. Bleomycin lung toxicity occurred in 43 percent of patients, and there was 18 percent mortality in affected patients. Grade ≥3 neutropenia was reported in 83 percent and grade ≥3 nonhematologic AEs in 44 percent.
BrECADD — BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) is an aggressive regimen that is favored by some experts for treating fit patients ≤60 years with adverse prognostic features.
BrECADD was superior to escalated BEACOPP (escBEACOPP; bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) in HD21, a phase 3 trial in patients with advanced-stage cHL or other adverse prognostic features [5], as discussed below.
No studies have directly compared BrECADD with N+AVD, and it is difficult to compare the S1826 and HD21 trials because of different inclusion criteria, endpoints, and toxicity profiles. Enrollment in HD21 was limited to patients 18 to 60 years, and it included patients with stage II unfavorable prognosis cHL. By contrast, S1826 enrolled patients ≥12 years and included only stages III to IV. BrECADD was associated with substantial hematologic toxicity, including 30 percent grade ≥3 anemia, 55 percent grade ≥3 thrombocytopenia, and 28 percent febrile neutropenia; 24 percent of patients received red blood cell (RBC) transfusions and 17 percent received platelet transfusions. Treatment with N+AVD is discussed above. (See 'Nivolumab plus AVD (preferred)' above.)
●Administration – BrECADD is administered in 21-day cycles, as follows:
•BV 1.8 mg/kg (up to 180 mg) intravenously (IV) on day 0
•Etoposide 150 mg/m² IV on days 1 to 3
•Cyclophosphamide 1250 mg/m² IV on day 1
•Doxorubicin 40 mg/m² IV on day 1
•Dacarbazine 250 mg/m² IV on days 2 to 3
•Dexamethasone 40 daily on days 1 to 4
Pegylated or nonpegylated G-CSF is given with each cycle. Doses of BV, etoposide, cyclophosphamide, and doxorubicin are adjusted, if needed, in subsequent treatment cycles.
●Toxicity – AEs include substantial cytopenias. The HD21 trial (described below) reported febrile neutropenia and anemia requiring RBC transfusions in more than one-quarter of patients [5]. Grade ≥3 organ-related AEs were uncommon with BrECADD.
●Outcomes – BrECADD was better tolerated and more effective than escBEACOPP in the HD21 trial of patients with advanced-stage cHL or other adverse prognostic features [5]. The trial included 1500 patients ≤60 years with stage III/IV cHL or stage II cHL with B symptoms and either a large mediastinal mass and/or extranodal lesions. Patients were randomly assigned to two 21-day cycles of BrECADD or escBEACOPP. Patients with complete response on PET received two additional cycles, while others received four additional cycles; 36 percent of patients required six cycles of BrECADD. Consolidative radiation therapy was given to 14 percent of patients for PET positivity at the end of six cycles of BrECADD. Four-year OS with BrECADD and escBEACOPP was 98.6 and 98.2 percent, respectively, but BrECADD achieved better four-year PFS (HR 0.66 [95% CI 0.45-0.97]). There were fewer grade ≥3 AEs with BrECADD (42 versus 59 percent; relative risk 0.72 [95% CI 0.65-0.80]).
BEACOPP — Because of its toxicity, escBEACOPP is generally restricted to fit patients <60 years. As discussed above, the HD21 trial demonstrated that BrECADD was superior to escBEACOPP in patients with advanced-stage cHL. (See 'BrECADD' above.)
There is no consensus protocol for the administration of escBEACOPP, but G-CSF must be given with each cycle. If escBEACOPP is to be administered, it should be given using a response-guided method, as applied in the HD18 trial [11].
Acute AEs include cytopenias, infection, nausea, and alopecia, and there is significant treatment-related mortality in older patients [12,13]. Late AEs include increased risk for second cancers and infertility [14-18].
RADIATION THERAPY —
Radiation therapy (RT) is not routinely used to treat patients with advanced-stage cHL.
There is no demonstrated benefit from consolidative RT after achieving complete response with chemotherapy in patients with bulky disease, as discussed below. (See 'Bulky disease' below.)
Consolidative RT can be given for persistent positron emission tomography (PET)-positive disease at the completion of chemotherapy. However, many experts biopsy the PET-positive site, and if persistent viable cHL is found, they manage the disease like relapsed/refractory cHL, as discussed separately. (See "Treatment of relapsed or refractory classic Hodgkin lymphoma".)
RT can provide effective palliation for frail patients who cannot tolerate chemotherapy. (See 'Frail patients' below.)
RT field and dose guidelines for the treatment of cHL have been published by the International Lymphoma Radiation Oncology Group (ILROG) [19].
SPECIAL SCENARIOS
Bulky disease — There is no persuasive evidence that consolidative radiation therapy (RT) is beneficial for patients with bulky cHL (>10 cm or >1/3 of the chest diameter) who achieve a complete response (CR) to chemotherapy.
There was no difference in outcomes in a phase 3 trial (HD0607) when RT was omitted in patients with bulky disease who achieved a CR with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) [20]. For 296 patients with stage IIB to IV cHL and a nodal mass ≥5 cm who had CR on positron emission tomography (PET) after two cycles of ABVD and after six cycles of ABVD, random assignment to consolidative RT versus no RT did not affect six-year progression-free survival (PFS). Subgroup analysis found no effect of consolidative RT for patients with masses of 5 to 7 cm, 8 to 10 cm, or >10 cm.
Frail patients — There is no consensus treatment for patients with poor performance status or substantial comorbidities who are unlikely to tolerate N+AVD (nivolumab plus doxorubicin, vinblastine, dacarbazine) or sequential BV (brentuximab vedotin)-AVD-BV, as discussed above. (See 'Initial treatment' above.)
Treatment options are limited in this setting, and there should be little expectation of prolonged disease control [21]. Treatment options include PD-1 blockade or BV as a single agent or combined with nivolumab or dacarbazine [22]. Other single-agent chemotherapy or RT can also be used to palliate symptoms, as discussed separately. (See "Treatment of relapsed or refractory classic Hodgkin lymphoma".)
Pregnancy — The management of cHL in patients who are pregnant must consider the effects of treatment on the fetus and the patient.
Management is informed by the trimester when cHL is diagnosed, as discussed separately. (See "Management of classic Hodgkin lymphoma during pregnancy".)
People living with HIV — The management of cHL in people living with HIV (PLWH) is complicated by their immunocompromised state and requires specific treatment for the HIV infection. The S1826 trial that treated patients with advanced-stage cHL using N+AVD allowed enrollment of PLWH [3]; the S1826 trial is discussed above. (See 'Nivolumab plus AVD (preferred)' above.)
Treatment of cHL in PLWH is discussed in more detail separately. (See "HIV-related lymphomas: Treatment of systemic lymphoma" and "HIV infection and malignancy: Management considerations", section on 'Hodgkin lymphoma'.)
CLINICAL TRIALS —
Often there is no better therapy to offer a patient than enrollment onto a well-designed, scientifically valid, peer-reviewed clinical trial. Additional information and instructions for referring a patient to an appropriate research center can be obtained from the United States National Institutes of Health (www.clinicaltrials.gov).
SOCIETY GUIDELINE LINKS —
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Management of Hodgkin lymphoma".)
INFORMATION FOR PATIENTS —
UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient education" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Hodgkin lymphoma in adults (Beyond the Basics)" and "Patient education: Hematopoietic cell transplantation (bone marrow transplantation) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Description – Initial treatment of classic Hodgkin lymphoma (cHL) is guided by disease stage and prognostic features:
•Advanced stage – Stage III or stage IV
•Limited stage – Stage I or stage II
●Pretreatment – The patient should be evaluated for disease-related symptoms, medical comorbidities, disease stage, and prognostic group.
•Clinical – History and physical examination assess symptoms, comorbid illnesses, and performance status (table 1). (See 'Clinical and laboratory studies' above.)
•Stage – Disease stage is based on the Lugano criteria (table 2) using clinical evaluation and positron emission tomography (PET)/CT.
•Prognosis – Prognosis is assessed using the International Prognostic Score (IPS) (table 3) (calculator 1). (See 'Prognosis' above.)
●Initial treatment
•Nivolumab plus AVD (preferred) – For initial treatment of advanced-stage cHL, we suggest N+AVD (nivolumab plus doxorubicin, vinblastine, dacarbazine), rather than BV+AVD (brentuximab vedotin, doxorubicin, vinblastine, dacarbazine) (Grade 2B). (See 'Nivolumab plus AVD (preferred)' above.)
N+AVD is contraindicated in patients with rheumatoid arthritis, inflammatory bowel disease, and other autoimmune illnesses that require immunosuppressive therapy.
Some experts offer BrECADD (BV, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) for fit patients with advanced-stage cHL and adverse prognostic features; BrECADD is restricted to patients ≤60 years because of toxicity. No studies have directly compared BrECADD with N+AVD. (See 'BrECADD' above.)
•Alternatives – When nivolumab is not suitable or available, the preferred initial treatment varies by age and comorbidities.
-≤60 years – When N+AVD is not suitable/available for patients ≤60 years, we generally treat with BV+AVD.
When neither N+AVD nor BV+AVD is suitable/available, we treat using the RATHL strategy (two cycles of ABVD [doxorubicin, bleomycin, vinblastine, dacarbazine], followed by four cycles of AVD in patients with a complete response [CR]) or with BrECADD, as discussed above. (See '≤60 years' above.)
->60 years – When N+AVD is not suitable/available for patients >60 years, we generally treat with sequential BV-AVD-BV. (See 'Sequential BV-AVD-BV' above.)
●Response assessment
•Treatment response – PET is repeated after the completion of planned chemotherapy to document response. (See 'Treatment response' above.)
-CR – For PET scores 1 to 3, proceed to surveillance.
-Less than CR – Biopsy to evaluate the patient for refractory disease; if confirmed, treat as discussed separately. (See "Treatment of relapsed or refractory classic Hodgkin lymphoma".)
•Surveillance – Patients are monitored for relapse and treatment-related adverse effects.
●Treatments – Treatment regimens are described above:
•(See 'N+AVD' above.)
•(See 'BV+AVD' above.)
•(See 'Sequential BV-AVD-BV' above.)
•(See 'ABVD' above.)
•(See 'BrECADD' above.)
•(See 'BEACOPP' above.)
●Radiation therapy (RT) – RT is not routinely used to treat patients with advanced-stage cHL. (See 'Radiation therapy' above.)
●Special scenarios – There is no persuasive evidence that consolidative RT is beneficial for patients with bulky cHL. The management of bulky disease, frail patients, and other special scenarios are described above. (See 'Special scenarios' above.)
ACKNOWLEDGMENTS —
The editorial staff at UpToDate would like to acknowledge Steven Horwitz, MD, and Joachim Yahalom, MD, who contributed to earlier versions of this topic review.
