Hodgkin Lymphoma
Classical HL and nodular lymphocyte-predominant HL
DefinitionClick to collapse
Hodgkin lymphoma (HL) is an uncommon malignancy of B-cell origin. The World Health Organization (WHO) classification divides HL into two main types: classic Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL). CHL accounts for 95% of cases in Western countries, while NLPHL accounts for 5%. CHL is characterized by the presence of Reed-Sternberg cells in an inflammatory background, whereas NLPHL is characterized by the presence of lymphocytic-histiocytic cells, sometimes termed popcorn cells, and lacks Reed-Sternberg cells. The disease typically involves lymph nodes and can spread to other lymphoid tissues and organs. The staging is based on the Ann Arbor system, which divides each stage into subcategories A and B, the latter for presence of B symptoms (unexplained fevers >38°C, drenching night sweats, or weight loss >10% of body weight within 6 months of diagnosis). Patients are usually classified into three groups: early-stage favorable, early-stage unfavorable, and advanced-stage disease. [MS-2, MS-3]
EpidemiologyClick to collapse
SubtypesClick to collapse
Classic Hodgkin Lymphoma (CHL)
CHL is divided into four histologic subtypes based on the WHO classification: nodular sclerosis CHL, mixed cellularity CHL, lymphocyte-depleted CHL, and lymphocyte-rich CHL. CHL is characterized by the presence of Reed-Sternberg cells in an inflammatory background. The typical immunophenotype for CHL is CD15+, CD30+, PAX-5+ (weak); CD3-, CD20- (majority), CD45-, CD79a-. Epstein-Barr encoding region in situ hybridization (EBER-ISH) is recommended at initial diagnosis, and CHL can be EBER+ or EBER-. [HODG-1A, MS-2]
Nodular Lymphocyte-Predominant Hodgkin Lymphoma (NLPHL)
NLPHL is characterized by an indolent course and occasional late relapse. It lacks Reed-Sternberg cells but is characterized by the presence of lymphocytic-histiocytic cells (LP or popcorn cells). The typical immunophenotype for NLPHL is CD20+, CD45+, CD79a+, BCL6+, PAX-5+; CD3-, CD15-, CD30-. EBER-ISH is negative for NLPHL. The immunoarchitectural pattern should be specified as typical (subtypes A or B) or variant (subtypes C, D, E, or F), with variant patterns associated with advanced-stage disease and a higher risk of relapse. [HODG-11, HODG-1A, MS-24]
Molecular PathogenesisClick to collapse
The provided NCCN guideline does not include detailed information on specific genomic events, driver mutations, signaling pathways, or chromosomal abnormalities in Hodgkin lymphoma. The discussion focuses on clinical management, diagnosis, staging, and treatment. Therefore, this section cannot be populated from the source text.
Risk FactorsClick to collapse
Age
Bimodal age distribution with peaks at 15-30 years and ≥55 years. The prognosis is worse for patients >60 years.
Epstein-Barr Virus (EBV) infection
EBV+ disease is more frequent in older patients and in certain CHL subtypes (e.g., mixed cellularity). EBER-ISH testing is recommended at diagnosis. [HODG-1A, MS-20]
Human Immunodeficiency Virus (HIV) infection
HIV testing is recommended in the workup for HL. HL is an AIDS-defining illness. [HODG-1]
Immunosuppression
Conditions or treatments that suppress the immune system are associated with an increased risk of HL.
Family history
Selection of treatment (CMT vs. chemotherapy alone) should be based on family history of cancer or cardiac disease. [HODG-4, HODG-5A]
Clinical FeaturesClick to collapse
Typical Presentation
Hodgkin lymphoma is an uncommon malignancy of B-cell origin with two peaks of incidence: ages 15–30 years and adults aged ≥55 years [1]. The classic presentation involves painless lymphadenopathy, most commonly in the cervical, supraclavicular, or mediastinal regions. Patients may present with B symptoms including unexplained fevers >38°C, drenching night sweats, or weight loss >10% of body weight within 6 months of diagnosis. Associated symptoms include alcohol intolerance, pruritus, fatigue, and impaired performance status. CHL accounts for 95% of Hodgkin lymphoma in Western countries, while NLPHL accounts for approximately 5% [3]. CHL is characterized by Reed-Sternberg cells in an inflammatory background, whereas NLPHL is characterized by lymphocytic-histiocytic (LP or "popcorn") cells and lacks Reed-Sternberg cells [1,3]. The majority of patients with CHL present with early-stage disease, but a significant proportion present with advanced-stage disease involving lymph node regions on both sides of the diaphragm.
Symptoms
B symptoms
Unexplained fevers >38°C, drenching night sweats, or weight loss >10% of body weight within 6 months prior to diagnosis
Alcohol intolerance
Pain or discomfort at sites of lymphoma involvement triggered by alcohol consumption
Pruritus
Generalized or localized pruritus that may be severe and debilitating
Fatigue
Significant fatigue impacting performance status
Night sweats
Drenching sweats that may require changing bedding, distinct from mild nocturnal perspiration
Weight loss
Unexplained weight loss >10% of body weight within 6 months of diagnosis
Fever
Unexplained fever >38°C not attributable to infection
Signs
Painless lymphadenopathy
Most commonly cervical, supraclavicular, or mediastinal; may be firm, non-tender, and matted
Mediastinal mass
May be detected on chest radiograph; bulky mediastinal disease defined as MMR >0.33 or MTR >0.35
Hepatosplenomegaly
Enlargement of liver and/or spleen on physical examination or imaging
Splenomegaly
Splenic involvement classified as E-lesion or stage IIIS depending on pattern
Red FlagsClick to collapse
Unexplained fevers >38°C suggesting B symptom disease
Drenching night sweats requiring bedding change
Unexplained weight loss >10% of body weight within 6 months
Large mediastinal mass with compressive symptoms (superior vena cava syndrome, airway compromise)
Severe symptoms or organ compromise during pregnancy requiring urgent multidisciplinary management
Alcohol-induced pain at sites of lymphoma involvement (highly specific)
Severe pruritus interfering with quality of life
Rapidly enlarging lymph nodes
Bulky disease (>10 cm adenopathy or MMR >0.33/MTR >0.35)
InvestigationsClick to collapse
Diagnostic
Excisional lymph node biopsy
Gold standard for diagnosis; provides sufficient tissue for histopathological and immunohistochemical evaluation
Core needle biopsy
May be adequate if diagnostic when excisional biopsy is not feasible
Fine-needle aspiration (FNA)
Generally insufficient for diagnosis alone; may be used in combination with immunohistochemistry if judged diagnostic by expert hematopathologist or cytopathologist
Immunohistochemistry (IHC) panel
Essential for subtyping HL; CHL: CD15+, CD30+, PAX-5+ (weak); CD3-, CD20- (majority), CD45-, CD79a-; NLPHL: CD20+, CD45+, CD79a+, BCL6+, PAX-5+; CD3-, CD15-, CD30-
EBER-ISH (Epstein-Barr encoding region in situ hybridization)
Recommended at initial diagnosis; CHL is typically EBER+/- while NLPHL is EBER-
Complete blood count (CBC) with differential
Baseline hematologic assessment; may reveal cytopenias, lymphocytopenia, or leukocytosis
Erythrocyte sedimentation rate (ESR)
Prognostic factor for early-stage disease; used in unfavorable risk factor classification (≥50 mm/hr if A; ≥30 mm/hr if B)
Comprehensive metabolic panel
Assessment of renal and hepatic function prior to treatment; includes LDH and liver function tests
LDH
Prognostic biomarker; elevated in more aggressive disease
Liver function tests
Baseline hepatic assessment before chemotherapy
HIV testing
HL in HIV-positive patients requires modified staging and management approach; see NCCN Guidelines for Cancer in People with HIV
Hepatitis B/C testing
Encouraged for patients with risk factors or unusual disease presentations
Staging
FDG-PET/CT scan
Recommended for initial staging and restaging; essential for response assessment; should be obtained no longer than 1 month prior to therapy initiation
Diagnostic contrast-enhanced CT
Useful in selected cases; at minimum include areas identified as abnormal on FDG-PET/CT; CT component of conventional FDG-PET/CT is often not IV contrast-enhanced
Chest x-ray (PA)
Encouraged especially for large mediastinal masses; standard CXR is best for assessing mediastinal bulk using MMR or MTR
Abdominal ultrasound
Alternative staging imaging during pregnancy when CT and FDG-PET should be avoided
MRI without gadolinium
Alternative staging imaging during pregnancy; may be used for select sites including brain, spine, or specific extranodal sites
FDG-PET/MRI (skull base to mid-thigh) without contrast
Alternative anatomical imaging modality that may be considered
Biomarkers
Deauville 5-point scale (5-PS) score
Visual scoring system for FDG-PET/CT interpretation based on uptake in involved sites relative to mediastinal blood pool and liver; scores 1-3 are considered negative, 4-5 are positive
IPS (International Prognostic Score)
Seven adverse prognostic factors for stage III-IV disease: age ≥45, male sex, stage IV, albumin <4 g/dL, hemoglobin <10.5 g/dL, leukocytosis (WBC ≥15,000/mm3), lymphocytopenia (lymphocyte count <8% of WBC and/or <600/mm3)
StagingClick to collapse
Ann Arbor staging system with Cotswolds modification [6,7]; each stage divided into A (no systemic symptoms) and B (presence of B symptoms: unexplained fevers >38°C, drenching night sweats, or weight loss >10% body weight within 6 months)
T Categories
| Stage | Description |
|---|---|
| N/A | Hodgkin lymphoma does not use a formal TNM staging system. Staging is based on the Ann Arbor classification system, which defines stage based on extent of lymph node and extranodal involvement relative to the diaphragm. |
N Categories
| Stage | Description |
|---|---|
| Stage I | Involvement of a single lymph node region (I) or localized involvement of a single extralymphatic organ or site (IE) |
| Stage II | Involvement of two or more lymph node regions on the same side of the diaphragm (II) or localized involvement of a single associated extralymphatic organ or site and its regional lymph node(s), with or without involvement of other lymph node regions on the same side of the diaphragm (IIE). Number of lymph node regions may be indicated by subscript (e.g., II3) |
| Stage III | Involvement of lymph node regions on both sides of the diaphragm (III), which may also be accompanied by localized involvement of an associated extranodal organ or site (IIIE), by involvement of the spleen (IIIS), or by both (IIIE+S) |
| Stage IV | Disseminated (multifocal) involvement of one or more extranodal organs, with or without associated lymph node involvement, or isolated extranodal organ involvement with distant (nonregional) nodal involvement |
M Categories
| Stage | Description |
|---|---|
| N/A | Hodgkin lymphoma uses extranodal designations (E, S, X) rather than formal M categories. E = extranodal extension; S = splenic involvement; X = bulky disease. Stage IV represents disseminated extranodal involvement. |
Stage Groupings
| Group | Criteria | Clinical Meaning | Five Yr Survival | Treatment Intent |
|---|---|---|---|---|
| Stage IA/IIA Favorable Disease (GHSG criteria) | Stage I-II with no unfavorable factors: MMR ≤0.33, ≤2 nodal regions, ESR <50 mm/hr (or <30 mm/hr if B symptoms), no E-lesions, no bulky disease >10 cm | Limited disease with favorable prognosis; amenable to abbreviated chemotherapy plus ISRT or chemotherapy alone | 5-year PFS approximately 93-94% with 2 cycles ABVD + ISRT 20 Gy (HD16 data); 5-year OS approximately 97% | Curative |
| Stage IA/IIA Favorable Disease (EORTC criteria) | Stage I-II with ≤3 nodal regions involved (including mediastinum and bilateral hila as single region; infraclavicular/subpectoral combined with axilla), no bulky mediastinal disease, no ESR ≥50 mm/hr, no B symptoms, no E-lesions | Limited disease favorable prognosis; broader favorable criteria than GHSG | 3-year PFS approximately 94.6% with CMT (RAPID data); 5-year PFS approximately 98.8% with ABVD + INRT (H10F data) | Curative |
| Stage I/II Unfavorable Disease | Stage I-II with any unfavorable factor: B symptoms, bulky mediastinal disease (MMR >0.33 or MTR >0.35), ESR ≥50 mm/hr (or ≥30 mm/hr if B), ≥3 nodal regions (GHSG) or ≥4 nodal regions (EORTC/NCCN), E-lesions, or adenopathy >10 cm | Limited disease with adverse prognostic features; requires more intensive treatment | 2-year PFS approximately 97.3% with BV-AVD + ISRT (BREACH data); PFS outcomes improved with BrECADD for stage IIB with large mediastinal mass | Curative |
| Stage III-IV Advanced Disease | Stage III: lymph node regions on both sides of the diaphragm; Stage IV: disseminated extranodal involvement. With or without bulky disease, B symptoms, or elevated IPS | Advanced-stage disease requiring systemic chemotherapy; IPS may further stratify prognosis | 2-year PFS approximately 92% with nivolumab-AVD (SWOG S1826); 4-year PFS approximately 94.3% with BrECADD (HD21); 6-year OS approximately 93.9% with BV-AVD (ECHELON-1) | Curative |
| Stage III-IV (Older adults/unfit) | Stage III-IV in patients >60 years or those unfit for intensive therapy; associated with poorer outcomes, more B symptoms, mixed cellularity histology, EBV+ disease, and medical comorbidities | Requires modified treatment approach with reduced toxicity regimens; limited prospective data for alternatives to standard therapies | 2-year PFS approximately 89% with nivolumab-AVD in patients ≥60 years (S1826 subset analysis); 2-year EFS approximately 80% with sequential BV-AVD (Evens et al) | Curative, with goal of minimizing toxicity while maximizing efficacy |
Staging Pearls
- The number of lymph node regions involved is indicated by subscript (e.g., II3) per Ann Arbor classification
- GHSG and EORTC define lymph node regions differently from Ann Arbor sites: both bundle mediastinum and bilateral hila as single region; GHSG combines infraclavicular/subpectoral with cervical; EORTC combines infraclavicular/subpectoral with axilla
- FDG-PET scans may demonstrate increased avidity in lymphoid tissue unrelated to lymphoma in persons with HIV, particularly if HIV is not well-controlled
- Mediastinal bulk is best assessed with standard CXR as practice-changing studies used this modality; if CXR not obtained, CT can be used with single mass >1/3 maximum transverse diameter of chest or any mass >10 cm
- FDG-PET is useful for upstaging in stage I-II disease; if FDG-PET positivity is found outside already identified disease, further clinical investigation is recommended
- In most instances, if FDG-PET/CT displays homogeneous marrow uptake (thought to be secondary to cytokine release), bone marrow involvement is not assumed; if multifocal (≥3) skeletal lesions are present, marrow may be assumed to be involved
- NLPHL staging is separate from CHL with different natural history and treatment approach; NLPHL has indolent course and occasional late relapse
- B symptoms are defined as: unexplained fevers >38°C, drenching night sweats, or weight loss >10% of body weight within 6 months of diagnosis
- Patients with bulky disease, subdiaphragmatic disease, or splenic involvement in NLPHL have high risk for initial or later transformation to large cell lymphoma
- Favorable risk factors differ between GHSG and EORTC criteria, affecting classification and treatment approach for early-stage disease
SurveillanceClick to collapse
Clinical Follow Up Schedule
- History & physical: Every 3-6 months for 1-2 years, then every 6-12 months until year 3, then annually thereafter [26].
- Annual influenza vaccine and other vaccines as clinically indicated (see NCCN Guidelines for Survivorship) [26].
Imaging Strategy
- Surveillance FDG-PET/CT is not recommended due to high false-positive rate [29].
- Diagnostic CT (contrast-enhanced) may be obtained at 3-6 month intervals for up to 2 years as clinically indicated, or after 2 years if relapse is suspected [26].
- FDG-PET/CT only indicated if evaluating for potential relapse based on symptoms or clinical findings [26].
Laboratory Monitoring
- CBC, ESR (if elevated at diagnosis), chemistry profile: Annually [26].
- Thyroid function tests (TFTs): At least annually if thyroid was in RT field [26].
- Lipid panel: Biannually for cardiovascular risk assessment [26].
- Fasting glucose: Annually for diabetes screening if abdominal RT [19].
Supportive Follow Up
- Counseling on reproduction, health habits, cardiovascular risk reduction, breast awareness, skin cancer risk, and end-of-treatment summary [26].
- Consider referral to survivorship clinic and coordination with PCP [26].
- Screen for psychosocial distress using NCCN Distress Thermometer [25].
ComplicationsClick to collapse
Disease-Related
| Complication | Management |
|---|---|
| Transformation to aggressive B-cell lymphoma (e.g., diffuse large B-cell lymphoma) | Biopsy recommended for suspected relapse, especially at intra-abdominal or splenic sites. Treatment per NCCN Guidelines for B-Cell Lymphomas. |
| B symptoms (fever, night sweats, weight loss >10%) | Part of staging and prognostic assessment; treated with systemic therapy. |
| Large mediastinal mass with potential for airway compromise or superior vena cava syndrome | Urgent systemic therapy and/or radiation; consider steroids for rapid cytoreduction. |
Supportive CareClick to collapse
Supportive care is integral to HL management, focusing on mitigating treatment-related toxicity, preserving quality of life, and addressing long-term survivorship issues. A multidisciplinary approach including oncology, fertility, cardiology, and psychosocial support is essential.
Nutritional assessment and support are recommended for patients with poor intake, significant weight loss (>10%), or ongoing cytotoxic therapy. Consult dietitian as needed.
Regimen-specific antiemetic prophylaxis is recommended. For ABVD and similar regimens: 5-HT3 antagonist (ondansetron) +/- dexamethasone. For highly emetogenic regimens (e.g., escalated BEACOPP): 5-HT3 antagonist + NK1 receptor antagonist (aprepitant) + dexamethasone. For pregnant patients, ondansetron and metoclopramide are preferred [23].
G-CSF is not recommended with ABVD due to low neutropenia risk. It is recommended with BrECADD, BV-AVD, and other regimens with high febrile neutropenia risk. Primary prophylaxis should be considered for regimens with >20% risk of febrile neutropenia [24].
Not routinely specified for HL, but consider in patients with risk factors (e.g., immobilization, central venous catheters).
Pain assessment and management per NCCN Guidelines for Adult Cancer Pain. Address disease-related pain (e.g., bulky masses) and treatment-related pain (e.g., neuropathy, mucositis).
Distress screening with NCCN Distress Thermometer and Problem List is recommended at diagnosis and during treatment. Refer to social work, psychiatry, or supportive care services as needed [25].
Oral health assessment prior to treatment, especially if RT to head/neck region. Use fluoride trays if salivary glands in RT field to prevent xerostomia and dental caries.
PrognosisClick to collapse
Hodgkin lymphoma (HL) is among the most curable malignancies with modern treatments. The 5-year relative survival rates for patients diagnosed between 2014 and 2020 were 88.6% for all ages. Cure rates for HL have increased so markedly that overriding treatment considerations often relate to long-term toxicity. The prognosis is generally excellent for early-stage disease and remains favorable for advanced-stage disease with contemporary therapies [1].
By Stage
| Stage | Five Yr Survival | Context |
|---|---|---|
| Early-stage favorable (Stage I-IIA) | >95% | Excellent prognosis with combined modality therapy or chemotherapy alone [2]. |
| Early-stage unfavorable (Stage I-II) | ~90% | Prognosis remains excellent with appropriate risk-adapted therapy [2]. |
| Advanced-stage (Stage III-IV) | ~85% | Prognosis has significantly improved with modern regimens like nivolumab-AVD and BrECADD [3,4]. |
| Relapsed/Refractory | Variable, ~40-80% post-HDT/ASCR | Outcomes depend on chemosensitivity, time to relapse, and ability to undergo autologous stem cell rescue (HDT/ASCR) [5]. |
Prognostic Factors
- International Prognostic Score (IPS) for advanced disease: 7 adverse factors (age ≥45, male, stage IV, albumin <4 g/dL, hemoglobin <10.5 g/dL, leukocytosis ≥15,000/mm³, lymphocytopenia <8% or <600/mm³). Each factor reduces survival by 7-8% per year [6].
- Unfavorable factors for Stage I-II disease: Age ≥50 years, ESR ≥50 mm/hr (or ≥30 with B symptoms), bulky mediastinal disease (MMR >0.33 or MTR >0.35), ≥4 nodal regions (NCCN/EORTC) or ≥3 (GHSG), extranodal (E) lesion, any B symptoms [2,7].
- For NLPHL: Advanced stage, age ≥45 years, low hemoglobin, and B symptoms are associated with worse overall survival [8].
Follow UpClick to collapse
Post Curative Treatment
After completion of therapy, follow-up should be coordinated with the primary care physician (PCP). A treatment summary including details of RT, OAR doses, and cumulative anthracycline dose should be provided. Follow-up with an oncologist is recommended due to risk of relapse and late effects [26].
Surveillance Rationale
Follow-up aims to: (1) Detect relapse early when potentially curative salvage therapy is possible; (2) Monitor for and manage long-term treatment effects (e.g., secondary malignancies, cardiovascular disease, endocrinopathies, infertility); (3) Provide survivorship counseling [26].
Late Effects Screening
- Cardiovascular disease: Annual blood pressure, aggressive management of risk factors. Consider ECHO at 1-year post-anthracycline and then at 5-10 year intervals. Consider carotid US at 10-year intervals if neck RT [26,27].
- Secondary malignancies: Annual breast screening (mammography + MRI) for individuals assigned female at birth with intact breast tissue who received mediastinal/axillary RT between ages 10-30 years, starting 8 years post-RT but not before age 25. Lung cancer screening per NCCN Lung Cancer Screening Guidelines for smokers/ex-smokers with thoracic RT [26].
- Thyroid dysfunction: Annual TSH if thyroid was in RT field [26].
- Fertility: Discuss family planning; evaluate for premature ovarian failure or gonadal dysfunction if indicated.
- Psychosocial: Screen for distress, address survivorship concerns.
Recurrence Patterns
Most relapses (80-90%) occur within the first 3-5 years after treatment. Late relapses (>5 years) are uncommon but possible, especially in NLPHL. Relapse risk is higher for advanced-stage, residual PET positivity after therapy, and certain histologies (e.g., mixed cellularity) [28].
Key TrialsClick to collapse
| Acronym | Full Name | Year | N | Intervention | Comparator | Population | Primary Endpoint | Key Result | Secondary Outcomes | Practice Change | Journal |
|---|---|---|---|---|---|---|---|---|---|---|---|
| SWOG S1826 | Nivolumab+AVD in Advanced-Stage Classic Hodgkin's Lymphoma | 2024 | 970 | Nivolumab-AVD ×6 cycles | BV-AVD ×6 cycles | Advanced-stage (III-IV) CHL, ages ≥12 years | 2-year PFS | 2-year PFS: 92% vs. 83%; HR 0.45 (95% CI, 0.30-0.65) | 2-year EFS: 90% vs. 81% (HR 0.50); 2-year OS: 99% vs. 98% (HR 0.39) | Established nivolumab-AVD as preferred first-line therapy for advanced-stage CHL. | New England Journal of Medicine |
| HD21 | Assessing the efficacy and tolerability of PET-guided BrECADD versus eBEACOPP in advanced-stage, classical Hodgkin lymphoma | 2024 | 1500 | PET2-adapted BrECADD (brentuximab vedotin, etoposide, cyclophosphamide, doxorubicin, dacarbazine, dexamethasone) + G-CSF | PET2-adapted escalated BEACOPP | Advanced-stage CHL, ages ≤60 years | 4-year PFS | 4-year PFS: 94.3% vs. 90.9%; HR 0.66 (95% CI, 0.46-0.95; P=.035) | Treatment-related morbidity: 42% vs. 59% (P<.0001); 4-year OS: 98.6% vs. 98.2% | BrECADD replaced escalated BEACOPP as preferred intensive regimen due to lower toxicity and non-inferior efficacy. | The Lancet |
| HD10 | Reduced treatment intensity in patients with early-stage Hodgkin's lymphoma | 2010 | 1370 | 2 cycles ABVD + 20 Gy IFRT | 4 cycles ABVD + 30 Gy IFRT (and other combinations) | Early-stage favorable CHL (no risk factors) | 5-year FFTF and OS | No significant differences among 4 arms in OS, FFTF, or PFS | 5-year OS: 97.1-97.7%; 5-year FFTF: 91.1-93.4% | Established 2 cycles ABVD + 20 Gy ISRT as standard for early-stage favorable HL. | New England Journal of Medicine |
| RAPID | Results of a trial of PET-directed therapy for early-stage Hodgkin's lymphoma | 2015 | 602 | 3 cycles ABVD → PET-negative → observation | 3 cycles ABVD → PET-negative → IFRT | Early-stage (IA-IIA) favorable CHL | 3-year PFS (intent-to-treat) | 3-year PFS: 90.8% vs. 94.6% (HR 0.44, 95% CI 0.19-1.01; P=.04) | 3-year OS: 99.0% vs. 97.1% | Supported CMT over observation for PET-negative early-stage favorable HL, though OS not different. | New England Journal of Medicine |
| ECHELON-1 | Overall survival with brentuximab vedotin in stage III or IV Hodgkin's lymphoma | 2022 | 1334 | BV-AVD ×6 cycles | ABVD ×6 cycles | Advanced-stage (III-IV) CHL | 5-year PFS | 5-year PFS: 82.3% vs. 74.5%; HR 0.68 (95% CI, 0.56-0.84); 6-year OS: 93.9% vs. 89.4%; HR 0.59 (P=.009) | Lower pulmonary toxicity with BV-AVD; higher peripheral neuropathy. | Established BV-AVD as an option for advanced-stage HL, though not PET-adapted. | New England Journal of Medicine |
| KEYNOTE-204 | Pembrolizumab versus brentuximab vedotin in relapsed or refractory classical Hodgkin lymphoma | 2021 | 304 | Pembrolizumab | Brentuximab vedotin | Relapsed/refractory CHL after auto-HCT or ineligible for transplant | PFS by IRC | Median PFS: 13.2 vs. 8.3 months; HR 0.65 (95% CI, 0.48-0.88; P=.0027) | ORR: 64% vs. 42% | Established pembrolizumab as superior to BV in relapsed/refractory CHL. | The Lancet Oncology |
| AETHERA | Brentuximab vedotin as consolidation therapy after autologous stem-cell transplantation in patients with Hodgkin's lymphoma at risk of relapse or progression | 2018 | 329 | BV consolidation ×16 cycles | Placebo | High-risk CHL (primary refractory, CR1 <12 months, or extranodal/advanced relapse) post-ASCT | PFS | 5-year PFS: 59% vs. 41%; HR 0.52 (95% CI, 0.38-0.72) | No OS difference. | Supports BV consolidation post-ASCT for high-risk relapsed/refractory CHL. | Blood |
Clinical PearlsClick to collapse
- Pearl 1: Hodgkin lymphoma is highly curable; treatment decisions must balance cure with long-term toxicity, especially in young patients.
- Pearl 2: FDG-PET is essential for staging and response assessment using Deauville criteria (5-point scale); interim PET guides response-adapted therapy in some scenarios.
- Pearl 3: Nivolumab-AVD and BrECADD + G-CSF are now preferred first-line regimens for advanced-stage CHL, based on superior PFS in SWOG S1826 and HD21 trials, respectively [3,4].
- Pearl 4: Bleomycin pulmonary toxicity does not preclude consolidation thoracic RT; monitor with PFTs (DLCO ≥60% acceptable for bleomycin use).
- Pearl 5: PJP prophylaxis is required for all BV-containing regimens.
- Pearl 6: Surveillance FDG-PET/CT is not recommended due to high false-positive rate; clinical assessment is key.
- Pearl 7: Individuals assigned female at birth with intact breast tissue who received mediastinal/axillary RT between ages 10-30 require annual breast screening (mammography + MRI) starting 8 years post-RT but not before age 25.
- Pearl 8: NLPHL has a different natural history than CHL; transformation to aggressive lymphoma should be considered at relapse, especially with intra-abdominal or splenic disease.