What is Hodgkin Lymphoma?

Hodgkin lymphoma (formerly known as Hodgkin’s disease) is a rare type of lymphoma that accounts for only 0.5% of all new cancer cases in the United States.¹ The estimated number of new cases of Hodgkin lymphoma in 2023 is 8830, and the number of deaths is projected to reach 900.¹ Although most cancers affect older individuals, Hodgkin lymphoma tends to be a disease of young adults and is more common in male than female individuals.² 

Common symptoms of Hodgkin lymphoma include a set of systemic symptoms known as B symptoms often seen in lymphoma patients — such as drenching night sweats, unexplained weight loss, and unexplained fever — in addition to enlargement or swelling of the lymph nodes.³ 

Hodgkin lymphoma is classified into 2 types:  classical Hodgkin lymphoma (CHL) and nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL).⁴ CHL accounts for approximately 95% of Hodgkin lymphoma cases and can be divided further into specific subtypes.⁵ 

Hodgkin Lymphoma Treatment and Management

Treatment for Hodgkin lymphoma should be individualized for each patient. Guidelines established by the National Comprehensive Cancer Network (NCCN) for the management of Hodgkin lymphoma outline several commonly used therapies to be used alongside radiation therapy and allogeneic stem cell transplantation.⁴ 

Hodgkin Lymphoma Staging

Proper cancer staging is the first step in developing a comprehensive treatment plan for patients with Hodgkin lymphoma. The disease is staged using the Lugano classification system with stages I through IV based on imaging results from positron emission tomography (PET) scans or computed tomography (CT) scans.⁶ The letter E in limited-stage (I or II) disease denotes organ involvement outside of the lymphatic system. Advanced-stage disease is classified as stages III and IV. The letters A and B are used to denote either no symptoms (A) or the presence of fever, soaking night sweats, and/or unexplained weight loss (B). The letter S may be used to denote splenic involvement.⁷ 

The stages of Hodgkin lymphoma are as follows^6,8:

• Stage I: Cancer is found at a single lymphatic site (lymph node, spleen, thymus)
  • Stage IE: Cancer is found at a single extralymphatic site without nodal involvement (rarely seen in Hodgkin lymphoma)
• Stage II: Cancer is found at 2 or more lymph node regions on the same side of the diaphragm
  • Stage IIE: Cancer contiguously extends from the lymph nodes to nearby tissues with or without involvement of other lymph nodes on the same side of the diaphragm 
  • Stage II bulky: Development of tumors in areas outside of the chest that measure at least 10 cm or tumors at least one-third as wide as the chest; bulky disease may be denoted by the letter X⁸
• Stage III: Cancer is found in lymph node regions above and below the diaphragm or in regions above the diaphragm and the spleen
• Stage IV: Cancer is disseminated across 1 or more extralymphatic organs with or without nearby lymph node involvement; or any noncontiguous extralymphatic organ involvement in addition to stage II nodal disease; or any extralymphatic organ involvement in stage III nodal disease
  • Stage IV Hodgkin lymphoma may involve the bone marrow, lungs, liver, or cerebrospinal fluid

Hodgkin lymphoma can be further divided into favorable or unfavorable disease based on the presence of unfavorable risk factors, including bulky disease, the presence of B symptoms, an erythrocyte sedimentation rate of 50 mm/h or higher, and extranodal disease.⁹ 

Hodgkin Lymphoma Pharmacotherapy Recommendations

A broad range of pharmacotherapies are recommended for treating Hodgkin lymphoma. These treatments fall into 3 categories: chemotherapy, immunotherapy, and targeted therapy.

Chemotherapy

Chemotherapy agents are cytotoxic drugs that target rapidly dividing cells in the body by interfering with DNA synthesis, forcing them to undergo apoptosis (programmed cell death). Several chemotherapy agents are used to treat Hodgkin lymphoma, including⁴:

• Bendamustine
• Bleomycin
• Carboplatin
• Cisplatin
• Cyclophosphamide
• Cytarabine
• Dacarbazine
• Doxorubicin
• Etoposide
• Gemcitabine
• Ifosfamide
• Lenalidomide
• Procarbazine
• Vinblastine
• Vincristine

Immunotherapy

Immunotherapy represents a class of drugs that enhance the immune system’s effects against cancer. Immunotherapy agents — or immune checkpoint inhibitors — for Hodgkin lymphoma mainly target the programmed death-1/programmed death-1 ligand-1 (PD-1/PD-L1) axis, activating cytotoxic T cells and other immune cells to target and destroy cancerous cells. Pembrolizumab and nivolumab are both PD-1 inhibitors approved by the US Food and Drug Administration (FDA) for treating CHL.^10,11 

Brentuximab vedotin is an antibody-drug conjugate consisting of a monoclonal antibody covalently linked to a chemotherapy drug. It binds to CD30, a cell surface receptor found on lymphoma cells. Once the antibody is endocytosed, the toxic chemotherapy drug is released and triggers cellular death.¹² 

Rituximab is a monoclonal antibody that blocks CD20 on the surface of lymphoma cells. By binding to CD20, rituximab induces antibody-dependent cell-mediated cytotoxicity and complement-mediated cytotoxicity, resulting in lymphoma cell death.¹³ 

Targeted Therapy 

Although there currently are no FDA-approved targeted therapies for treating Hodgkin lymphoma, single-agent everolimus has been used off-label for treating relapsed or refractory disease. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor that causes cell growth arrest, triggering apoptosis.¹⁴ 

Recommended Treatment Doses and Uses

The NCCN has created pharmacotherapy guidelines based on the type and staging of Hodgkin lymphoma. Overall, treatment selection should be based on several factors, including the patient’s age, sex, comorbid conditions, personal and family history of cancer and cardiac disease, and location of the cancer.⁴ 

The following tables provide an overview of recommended treatment combinations including dosage and administration, as well as the duration of treatment for primary and relapsed/refractory CHL and NLPHL. 

Table 1. Management Guidelines for Chemotherapy Regimens for Hodgkin Lymphoma

Drug Combination	Dosage	Duration of Treatment	Recommended Use
ABVD	Doxorubicin 25 mg/m2Bleomycin 10 IU/m2Vinblastine 6 mg/m2Dacarbazine 275 mg/m2 All doses given on days 1 and 15	28-d cycle; repeated for 2 cycles total to treat nonbulky disease, 4 cycles total for bulky disease, or 6 cycles total for advanced-stage disease	Stages I and II unfavorable and bulky disease, stages I and II unfavorable non-bulky disease, stage III, and stage IV
BV-AVD	Brentuximab vedotin 1.2 mg/kg Doxorubicin 25 mg/m2Vinblastine 6 mg/m2 Dacarbazine 375 mg/m2  All doses given on days 1 and 15	28-d cycle for up to 6 cycles total	Stages III and IV CHL
Bendamustine	120 mg/m2 infused over 30 min on days 1 and 2	28-d cycle for 6-8 cycles	Second-line treatment in relapsed or refractory CHL and NLPHL; recommended for use in patients aged >60 y
CHOP R-CHOP*	Cyclophosphamide 750 mg/m2 on day 1Doxorubicin 50 mg/m2 on day 1 Vincristine 1.4 mg/m2 on day 1 (maximum 2-mg dose)Prednisone 100 mg orally on days 1-5 Same regimen as listed above with rituximab 375 mg/m2 on day 1	4-6 cycles	Stage I-II favorable disease and stage I-II unfavorable disease or stage III-IV disease in patients aged >60 y Advanced-stage NLPHL, and  second-line treatment in relapsed or refractory NLPHL
CVbP	Cyclophosphamide 500 mg/m2 on day 1Vinblastine 6 mg/m2 on days 1 and 8Prednisolone 40 mg/m2 on days 1-7	14- to 28-d cycles repeated for 3 cycles total	Early-stage NLPHL
DHAP DHAP + R*	Dexamethasone 40 mg IV infusion on days 1-4Cisplatin 100 mg/m2 on day 1Cytarabine 2 g/m2 on day 2 Same regimen as listed above with rituximab 375 mg/m2 on day 1	2 cycles total 2 cycles total for consolidation/salvage therapy; up to 6 cycles total for nontransplant-eligible patients	Relapsed or refractory CHL Relapsed or refractory NLPHL
Escalated BEACOPP	Cyclophosphamide1200 mg/m2 on day 1Doxorubicin 35 mg/m2 on day 1Etoposide 200 mg/m2 on days 1-3Procarbazine 100 mg/m2 on days 1-7Prednisone 40 mg/m2 on day 1-14Bleomycin 10 mg/m2 on day 8Vincristine 1.4 mg/m2 on day 8	21-d cycle for 2 to 8 cycles	Stage I/II unfavorable CHL in patients aged <60 years
GCD GCD + R*	Gemcitabine 1000 mg/m2 on days 1 and 8Cisplatin 75 mg/m2 on day 1Dexamethasone 40 mg/d oral on day 1-4 Same regimen as listed above with rituximab 375 mg/m2 on day 1	21-d cycle for 2 cycles total	Second-line therapy for relapsed or refractory CHL Second-line therapy for relapsed or refractory NLPHL*
ICE	Carboplatin AUC=5 (cannot exceed 800 mg per dose) on day 1Etoposide 100 mg/m2 on days 1-3Ifosfamide 5 g/m2 on day 2	14-d cycle repeated for 2 cycles total	Second-line therapy for relapsed or refractory CHL
Lenalidomide	25 mg/d by mouth on days 1-21	28-d cycle continued until disease progresses or intolerable toxicity develops	Relapsed or refractory CHL to ≥3 prior lines of therapy

From NCCN treatment recommendations.⁴ *Can be combined with rituximab. ABVD = doxorubicin, bleomycin, vinblastine, dacarbazine; CHL = classic Hodgkin lymphoma; CVbP = cyclophosphamide, vinblastine, prednisolone + rituximab; AUC = area under the curve; BEACOPP = bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, procarbazine; DHAP = dexamethasone, cisplatin, high-dose cytarabine; GCD = gemcitabine, cisplatin, dexamethasone; ICE = ifosfamide, carboplatin, etoposide; IV = intravenous; NLPHL = nodular lymphocyte-predominant Hodgkin lymphoma; R-CHOP = rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone.

Table 2. Management Guidelines for Immunotherapy for Hodgkin Lymphoma

Drug	Dosage	Administration	Duration of Treatment	Recommended Use
Nivolumab	240 mg every 2 wk or 480 mg every 4 wk	IV infusion over 30 min	Treat until disease progresses or until intolerable toxicity develops	Relapsed or refractory CHL
Pembrolizumab	200 mg every 3 wk or 400 mg every 6 wk	IV infusion over 30 min	Treat until disease progresses, intolerable toxicity develops, or for up to 2 y	Relapsed or refractory CHL
Brentuximab vedotin	1.2 mg/kg up to 120 mg every 2 wk in combination in chemotherapy for patients with previously untreated CHL 1.8 mg/kg up to 180 mg every 3 wk as monotherapy for patients with relapsed CHL and those undergoing consolidation therapy	IV infusion over 30 minutes	Treat until disease progresses, intolerable toxicity develops; a maximum of 12 cycles are given for previously untreated CHL and 16 cycles for relapsed CHL	Previously untreated stage III or IV CHL; relapsed CHL

From FDA-approved prescribing information.^15-17 CHL = classic Hodgkin lymphoma; IV = intravenous; NLPHL = nodular lymphocyte-predominant Hodgkin lymphoma.

Table 3. Management Guidelines for Targeted Therapy for Hodgkin Lymphoma

Drug	Dosage	Administration	Duration of Treatment	Recommended Use
Everolimus	10 mg/d	Oral	Treat until disease progresses or intolerable toxicity develops	Relapsed or refractory CHL, particularly in patients aged ≥60 y

From FDA-approved prescribing information.¹⁸ CHL: classic Hodgkin lymphoma.

Hodgkin Lymphoma: Monitoring Treatment

The most common reasons to modify or discontinue treatment for patients with Hodgkin lymphoma are intolerable side effects and adverse events due to toxicity. Chemotherapy agents and other cancer drugs often exhibit off-target cytotoxic effects, particularly on rapidly dividing cells throughout the body. Other factors to consider when monitoring treatment include drug metabolism and excretion, organ impairment, and other medications the patient is taking.

Table 4. Side Effect Profiles for Chemotherapy for Hodgkin Lymphoma

Drug	Most Common Adverse Events	Side Effects Necessitating Treatment Discontinuation or Modification	Drug-Drug Interactions	Special Population Considerations
Bendamustine	Nausea, vomiting, constipation, fever, fatigue and weakness, cough, headache, weight loss, anorexia, dyspnea (shortness of breath), rash, decreased blood cell count (lymphopenia, leukopenia, neutropenia, thrombocytopenia, anemia)	Infusion reaction or anaphylaxis, serious infections, myelosuppression, tumor lysis syndrome, severe skin reactions	CYP1A2 inhibitors or inducers	May be harmful to fetus; unknown risk with breastfeeding, may be harmful to infant; contraception is recommended for male and female individuals of reproductive age; do not use in patients with moderate to severe hepatic impairment and those with creatinine clearance <40 mL/min, use caution in those with lesser degrees of renal impairment
Bleomycin	Pulmonary fibrosis; skin redness, itching, and rash; hyperpigmentation; oral mucositis (stomatitis); nail changes; fever; chills; weight loss; anorexia; vomiting	Pulmonary toxicity, infusion reaction or anaphylaxis, renal toxicity, hepatic toxicity	Drugs with known nephrotoxicity can reduce bleomycin clearance	May be harmful to fetus; unknown risk with breastfeeding, may be harmful to infant; pulmonary toxicity is more common in patients aged ≥70 y
Carboplatin	Musculoskeletal pain, headache, back pain, joint pain, fatigue and weakness, rash, upper respiratory tract infection, cough, nausea, vomiting, abdominal pain, decreased appetite, diarrhea, fever	Infusion reaction or anaphylaxis	None indicated	Individuals should wait 5 mo after discontinuation before breastfeeding; may be harmful to fetus; contraception is recommended for female patients of reproductive age for ≥5 mo following the last dose
Cisplatin	Nausea, vomiting, peripheral neuropathy, myelosuppression, fever, increased risk of infection	Infusion reaction or anaphylaxis, ocular toxicity, ototoxicity, secondary leukemia, nephrotoxicity	Nephrotoxic and ototoxic drugs	Individuals should wait until treatment is completed before breastfeeding; may be harmful to fetus; contraception is recommended for male and female patients of reproductive age during treatment and for 11 mo after the last dose; use with caution in patients with renal impairment
Cyclophosphamide	Fever, alopecia, nausea, vomiting, diarrhea, neutropenia, febrile neutropenia	Immunosuppression and myelosuppression, serious infections, pulmonary toxicity, cardiotoxicity, renal and urinary tract toxicity, veno-occlusive liver disease	Protease inhibitors; natalizumab, ACE inhibitors, thiazide diuretics, anthracyclines, trastuzumab, G-CSF/GM-CSF, azathioprine, busulfan, amiodarone, indomethacin, pentostatin, cytarabine, zidovudine	Individuals should wait until treatment is completed before breastfeeding; may be harmful to fetus; contraception is recommended for male and female patients during treatment and for ≥4 mo after last dose; use with caution in patients with hepatic and renal impairment
Cytarabine	Headache, confusion, fatigue, nausea, vomiting, back pain, constipation, fever, convulsions, weakness, abnormal gait, arachnoiditis	Neurotoxicity, chemical arachnoiditis	Use caution when administering other cytotoxic agents intrathecally	Individuals should wait until treatment is completed before breastfeeding; may be harmful to fetus
Dacarbazine	Nausea, vomiting, anorexia, flu-like symptoms, alopecia, rashes, fatigue and weakness	Infusion reaction and anaphylaxis, hemopoietic depression, leukopenia, thrombocytopenia, myelosuppression, hepatotoxicity	None indicated	May be harmful to fetus; discontinue breastfeeding during treatment
Doxorubicin	Fever, fatigue and weakness, nausea, vomiting, anorexia, constipation, diarrhea, stomatitis, rash, decreased blood cell count, hand-foot syndrome (palmar-plantar erythrodysesthesia)	Hand-foot syndrome, stomatitis, thrombocytopenia or neutropenia, cardiomyopathy	None indicated	May be harmful to fetus, avoid prescribing in first trimester of pregnancy; discontinue breastfeeding during treatment; use with caution in patients with hepatic impairment
Etoposide	Neutropenia, nausea, vomiting, difficulty swallowing (dysphagia), abdominal pain, constipation, fever, optic neuritis	Myelosuppression, anaphylaxis, secondary leukemias	Warfarin	May be harmful to fetus; discontinue breastfeeding during treatment; contraception is recommended for male and female patients during treatment and for ≥4 mo and ≥6 mo, respectively, after last dose
Gemcitabine	Nausea, vomiting, leukopenia, neutropenia, thrombocytopenia, proteinuria, shortness of breath, rash, elevated aspartate transferase and alanine transferase levels	Infusion reaction, renal toxicity, pulmonary toxicity, hepatic toxicity, radiation toxicity	None indicated	May be harmful to fetus; discontinue breastfeeding during treatment; use with caution in patients with renal or hepatic impairment
Ifosfamide	Nausea, vomiting, anemia, hematuria, infection, alopecia, leukopenia, CNS toxicity	Myelosuppression, serious infections, urotoxicity, neurotoxicity, pulmonary toxicity, cardiotoxicity, secondary malignancy, veno-occlusive liver disease	CYP3A4 inhibitors and inducers	May be harmful to fetus; discontinue breastfeeding during treatment; adjust and monitor dosing in geriatric patients; use with caution in patients with renal or hepatic impairment
Lenalidomide	Fatigue, nausea, diarrhea, constipation, neutropenia, thrombocytopenia, leukopenia, anemia, fever, cough, rash, peripheral edema	Myelosuppression, serious infections, infusion reaction, tumor flare reaction, tumor lysis syndrome, hepatotoxicity, secondary malignancy, venous thromboembolism	Estrogen therapies, erythropoietin-stimulating agents, digoxin	May be harmful to fetus; contraception is recommended for male and female patients during treatment and for ≥1 mo after last dose; discontinue breastfeeding during treatment; use with caution in geriatric populations and those with renal impairment
Procarbazine	Nausea, vomiting, leukopenia, thrombocytopenia, diarrhea, constipation, hemorrhage, stomatitis, anemia, jaundice, abdominal pain, dry mouth, hematuria, depression	CNS depression, anaphylaxis or hypersensitivity reaction, myelosuppression	Use barbiturates, antihistamines, hypotensive agents, narcotics, and phenothiazine with caution to minimize CNS depression; limit MAO inhibitor use	May be harmful to fetus; discontinue breastfeeding during treatment
Vinblastine	Leukopenia, anemia, thrombocytopenia, alopecia, nausea, vomiting, abdominal pain, constipation, anorexia, diarrhea, paresthesias, headache, depression, hypertension, weakness and fatigue, bone pain, dizziness	Leukopenia less than 2000 WBC/mm3; neurologic toxicity	Phenytoin, CYP450 inhibitors, CYP3A inhibitors	May be harmful to fetus; use with caution in patients with hepatic impairment
Vincristine	Nausea, constipation, fever, fatigue, diarrhea, anemia, insomnia, decreased appetite, febrile neutropenia, peripheral neuropathy	Extravasation tissue injury, myelosuppression, neurotoxicity, tumor lysis syndrome, hepatic toxicity, fatigue, severe constipation and bowel obstruction	Strong CYP3A inhibitors or inducers; P-gp inhibitors or inducers	May be harmful to fetus; individuals should wait ≥1 wk after completing treatment before breastfeeding; contraception is recommended for male and female patients during treatment and ≥3 mo and ≥6 mo, respectively, after last dose; use with caution in patients with hepatic impairment

From FDA-approved prescribing information.^19-33 ACE = angiotensin-converting enzyme; CNS = central nervous system; G-CSF = granulocyte colony-stimulating factor; GM-CSF = granulocyte-macrophage colony-stimulating factor; MAO = monoamine oxidase; P-gp = P-glycoprotein; WBC = white blood cells.

Table 5. Side Effect Profiles for Immunotherapy for Hodgkin Lymphoma

Drug	Most Common Adverse Events*	Side Effects Necessitating Treatment Discontinuation or Modification	Drug-Drug Interactions	Special Population Considerations
Nivolumab	Musculoskeletal pain, diarrhea, nausea, skin itching and rash, nausea, vomiting, abdominal pain, decreased appetite, headache, fever, upper respiratory tract infection, back pain, urinary tract infection, fatigue and weakness	Infusion-related reaction or  anaphylaxis, immune-mediated reactions	None indicated	Individuals should wait 5 mo after discontinuation before breastfeeding; may be harmful to fetus
Pembrolizumab	Musculoskeletal pain, fatigue and weakness, decreased appetite, abdominal pain, nausea, constipation, shortness of breath, cough, fever	Infusion-related reaction or  anaphylaxis, immune-mediated reactions	None indicated	Individuals should wait 4 mo following discontinuation to before breastfeeding; may be harmful to fetus
Rituximab	Fever, neutropenia, chills, fatigue and weakness, upper respiratory tract infection, urinary tract infection, nausea, headache, diarrhea, peripheral edema, muscle spasms, depression	Tumor lysis syndrome, serious infections, bowel obstruction and perforation, renal toxicity	Renal toxicity when used with cisplatin	Individuals should way 6 mo following discontinuation before breastfeeding; may be harmful to fetus
Brentuximab vedotin	Upper respiratory tract infection, cough, rash, decreased blood cell count (thrombocytopenia, neutropenia), nausea, anemia, fatigue, peripheral sensory neuropathy, diarrhea, vomiting	Infusion-related reaction or anaphylaxis, toxic epidermal necrolysis, Stevens-Johnson syndrome, serious infections, tumor lysis syndrome	Strong CYP3A4 inducers or inhibitors, P-gp inhibitors, contraindicated for use with bleomycin due to pulmonary toxicity	Not recommended in people with severe renal impairment or moderate to severe hepatic impairment

From FDA-approved prescribing information.^34-37 *Reported in ≥20% of patients. P-gp = P-glycoprotein.

Table 6. Side Effect Profiles for Targeted Therapy for Hodgkin Lymphoma

Drug	Most Common Adverse Events	Side Effects Necessitating Treatment Discontinuation or Modification	Drug-Drug Interactions	Special Population Considerations
Everolimus	Fever, nausea, abdominal pain, diarrhea, rash, fatigue and weakness, headache, cough, decreased appetite, infections, edema, stomatitis, respiratory tract infection	Noninfectious pneumonitis, serious infections and myelosuppression, renal failure, infusion-related reaction, angioedema, stomatitis, metabolic disorders	P-gp  and moderate CYP3A4 inhibitors, P-gp and strong CYP3A4 inhibitors	May be harmful to fetus; contraception is recommended for male and female patients during treatment and for ≥1 mo and ≥2 mo, respectively, after last dose; individuals should wait 2 wk following discontinuation before breastfeeding; use with caution in patients with hepatic impairment

From FDA-approved prescribing information.¹⁸ P-gp = P-glycoprotein.

Treatment Guidelines

The NCCN has developed treatment guidelines for each stage of Hodgkin lymphoma and for patients with relapsed/refractory disease. These guidelines are further divided into recommendations for adults aged 18 years and older and for adults aged 60 years and older. Below is an outline of treatment guidelines based on these groupings.⁴ 

CHL in Adults Aged 18 Years and Older

Adults between the ages of 18 and 60 years are generally healthy and often do not have comorbid conditions. They can tolerate intensive chemotherapy regimens recommended for treating Hodgkin lymphoma. Deauville scores are used to report response to treatment. The NCCN recommendations are made following imaging tests based on a patient’s Deauville score. 

Stages I-II

Patients with stage I-IIA Hodgkin lymphoma with favorable nonbulky disease are recommended to undergo 2 cycles of ABVD followed by restaging with PET/CT. Following restaging, treatments may include radiation therapy (combined modality treatment [CMT] or, if preferred, only chemotherapy:

Recommendations for CMT:

• Deauville score of 1-2: 1 cycle of ABVD + radiation therapy
• Deauville score of 3: 2 cycles of ABVD + radiation therapy 

Recommendations for chemotherapy only:

• Deauville score of 1-2: 1 or 2 cycles of ABVD, with a preference for 2 cycles
• Deauville score of 3: 4 cycles of AVD
• Deauville score of 4: 2 additional cycles of ABVD followed by PET scan for restaging

Biopsy is recommended for patients with a Deauville score of 4-5 to inform treatment decisions. Patients with a negative biopsy should receive treatments outlined for those with a Deauville score of 4. Patients with a Deauville score of 5 after interim restaging are considered to have refractory disease. 

Stage I-II Unfavorable Disease 

Patients with stage I-II unfavorable bulky disease or those with B symptoms, adenopathy >10 cm, or mediastinal disease are recommended to undergo 2 cycles of ABVD followed by restaging with a PET scan. 

Following the first round of treatment and restaging, recommendations for patients with a Deauville score of 1-3 include:

• CMT: 2 additional cycles of ABVD (for a total of 4 cycles) followed by radiation therapy
• Chemotherapy alone: 4 cycles of AVD

Patients with a Deauville score of 4-5 are recommended to receive 2 cycles of escalated BEACOPP followed by restaging. Recommended follow-up treatments based on restaging include:

• Deauville score of 1-3: Radiation therapy (CMT) or 2 cycles of escalated BEACOPP (chemotherapy alone)
• Deauville score of 4-5: A biopsy is also recommended at this point to inform the next round of treatment (for patients with a negative biopsy, refer to treatment for Deauville score 1-3 listed above; for patients with a positive biopsy, consider treatment for refractory disease)

Stage III-IV

For patients with stage III-IV (advanced-stage disease), the preferred treatment options are 2 cycles of ABVD or 6 cycles of BV-AVD followed by restaging. 

Initial ABVD Treatment

Following 2 cycles of ABVD treatment and restaging, recommendations are as follows:

• Deauville score of 1-3: 4 cycles of AVD followed by patient monitoring
• Deauville score of 4-5: 3 cycles of escalated BEACOPP followed by restaging with fluorodeoxyglucose (FDG)-PET

For those who are treated with escalated BEACOPP and restaged, recommendations are as follows:

• Deauville score of 1-3: Continue therapy with 1 additional cycle of escalated BEACOPP alone or with radiation therapy 
• Deauville score of 4-5: Obtain a biopsy to inform the treatment plan (for patients with a negative biopsy, follow the recommendation for Deauville score 1-3; for patients with a positive biopsy, follow treatment for refractory disease)

Initial BV-AVD Treatment

Following 6 cycles of BV-AVD treatment and restaging with PET, recommendations are as follows:

• Deauville score of 1-3: Patients should be monitored for relapse
• Deauville score of 4-5: Obtain a biopsy to inform the treatment plan, for patients with a Deauville score of 5 and a positive biopsy, follow treatment for refractory disease

CHL in Adults Aged 60 Years and Older

Older adults with Hodgkin lymphoma tend to have poorer disease outcomes and prognosis. Intensive chemotherapy regimens used in younger populations are often too intense for this age group; therefore, treatment goals focus instead on maximizing treatment benefits while minimizing toxicity. Below is an outline for managing CHL in patients aged 60 years and older. 

Stage I-II Favorable Disease

The recommended treatment for early-stage favorable disease is 2 cycles of ABVD ± 2 cycles of AVD. Four cycles of CHOP may also be used. Bleomycin should be used with caution in this population and should be discontinued after 2 cycles of treatment. 

Stage I-II Unfavorable Disease or Stage III-IV Disease

Patients with early-stage unfavorable disease or late-stage disease may receive 2 cycles of ABVD followed by 4 cycles of AVD if their PET scan is negative following 2 cycles of ABVD. Those who have a positive PET scan following 2 cycles of ABVD require an individualized treatment plan. 

Other options for those with early-stage unfavorable disease include:

• 6 cycles of CHOP
• Brentuximab vedotin + dacarbazine
• Brentuximab vedotin followed by AVD

Relapsed or Refractory Disease in CHL

Disease outcomes and prognosis tend to be poor in older adults with relapsed or refractory Hodgkin lymphoma. There are no standard treatment recommendations; instead, single-agent therapy for palliative care is often the best approach. Examples of treatments for relapsed or refractory disease in CHL as suggested by the NCCN include:

• Brentuximab vedotin
• Bendamustine
• Nivolumab 
• Pembrolizumab 

NLPHL Treatment Recommendations

NLPHL is an indolent disease that may not require aggressive treatment. Treatment for early-stage NLPHL often involves radiation therapy. Patients with stage IA, IB, IIA bulky or noncontiguous, or IIB disease are treated with chemotherapy (ABVD, CHOP, or CVbP) plus radiation therapy with rituximab. 

For those with stage III-IV disease, a combination of chemotherapy and rituximab with or without radiation therapy is recommended. Restaging should be done in all patients after completing initial therapy. 

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27. US Food and Drug Administration. Highlights of prescribing information: Etopophos. Updated May 2017. Accessed April 26, 2023. 
28. US Food and Drug Administration. Highlights of prescribing information: Gemzar. Accessed April 26, 2023. 
29. US Food and Drug Administration. Highlights of prescribing information: Ifex. Updated March 2012. Accessed April 26, 2023. 
30. US Food and Drug Administration. Highlights of prescribing information: Revlimid. Updated June 2013. Accessed April 26, 2023. 
31. Matulane. Leadiant Biosciences, Inc. Updated November 14, 2022. Accessed April 26, 2023. 
32. Vinblastine sulfate. Fresenius Kabi USA, LLC. Updated December 31, 2019. Accessed April 26, 2023. 
33. US Food and Drug Administration. Highlights of prescribing information: Marquibo. Updated June 2020. Accessed April 26, 2023. 
34. US Food and Drug Administration. Highlights of prescribing information: Opdivo. Updated March 2022. Accessed April 26, 2023. 
35. US Food and Drug Administration. Highlights of prescribing information: Keytruda. Updated March 2021. Accessed April 26, 2023. 
36. US Food and Drug Administration. Highlights of prescribing information: Rituxan. Updated June 2021. Accessed April 26, 2023. 
37. US Food and Drug Administration. Highlights of prescribing information: Adcetris. Updated April 2014. Accessed April 26, 2023. 

Author Bio

Emily Wagner, MS earned a Bachelor of Science in biotechnology from the Rochester Institute of Technology in 2018 and a Master of Science in biomedical sciences with a focus in pharmacology from the University of Colorado Anschutz Medical Campus in 2020. During her thesis work, she studied non-small cell lung cancer and how the immune system plays a role in response to different treatments. Emily currently lives in Colorado where she enjoys the mountains, spending time with her dog, baking, and reading a good book.