Hodgkin's lymphoma medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sowminya Arikapudi, M.B,B.S. [2] Mohsen Basiri M.D.

Overview

Hodgkin lymphoma is considered as curable cancer, however, treatment-related toxicities for this disease can be associated with significant long-term complications. Selection of treatment protocol for Hodgkin's lymphoma depends on the type, the stage at diagnosis, age, and size of tumor. Combined modality therapy including use of chemotherapy and radiation therapy (RT) is the treatment of choice in patients with early-stage classic Hodgkin's Lymphoma.

Medical Therapy

Hodgkin lymphoma is considered as curable cancer, however, treatment-related toxicities for this disease can be associated with significant long-term complications. Selection of treatment protocol for Hodgkin's lymphoma depends on the type, the stage at diagnosis, age, and size of tumor.

• Disease at stage I or stage II is considered early stage. In addition, other clinical features, such as age, absence or presence of B symptoms, number of involved sites, and size of lymphadenopathy are used by experts to stratify Hodgkin's lymphoma into favorable and unfavorable subtypes.
  • The definitions of favorable disease are proposed by the European Organization for the Research and Treatment of Cancer (EORTC) are following:

• • • Age under 50 years
    • No large mediastinal adenopathy
    • ESR of less than 50 mm/h and no B symptoms (or an ESR of less than 30 mm/h with B symptoms)
    • Disease limited to three or fewer regions of involvement

• • The criteria are used by the German Hodgkin Study Group (GHSG) for definitions of favorable disease include:

• • • No more than two sites of involvement
    • No extranodal extension
    • No mediastinal mass measuring one-third the maximum thoracic diameter or greater
    • ESR less than 50 mm/h (less than 30 mm/h if B symptoms present)

• Patients without these criteria are considered to have unfavorable stratification.

• Combined modality therapy including use of chemotherapy and radiation therapy (RT) is the treatment of choice in patients with early-stage classic Hodgkin's Lymphoma.

The National Comprehensive Cancer Network (NCCN) guideline for treatment of Hodgkin’s Lymphoma:

Favorable stage I to II classic Hodgkin’s Lymphoma

• Preferred regimen:ABVD (doxorubicin [Adriamycin]/ bleomycin/ vinblastine/ dacarbazine) regimen in two or four cycles for patients :
• Doxorubicin 25 mg/m² IV + Bleomycin 10 units/m² IV + Vinblastine 6 mg/m² IV + Dacarbazine 375 mg/m² IV on days 1 and 15. Two cycles for patients with fewer than two involved sites, and four cycles for other patients.
• Alternative regimen: Stanford V regimen (doxorubicin, vinblastine, mechlorethamine [or cyclophosphamide], etoposide, vincristine, bleomycin, and prednisone). or alternatively patients undergo an 8-week

Two cycles of ABVD followed by 20 Gy radiation therapy is suggested for patients with favorable stage I to II HL, as defined by The European Society for Medical Oncology (ESMO) guidelines, or doing PET-CT scanning after two cycles of ABVD. If PET-CT result is positive, then patients receive two cycles of BEACOPPesc (bleomycin/ etoposide/ doxorubicin/ cyclophosphamide/ vincristine/ procarbazine/ prednisone in escalated dose) followed by 30 Gy RT. PET-CT negative patients need one cycle of BEACOPPesc followed by 20 Gy radiotherapy (RT).

For treatment of non-bulky classic Hodgkin's Lymphoma at unfavorable stage I-II, the National Comprehensive Cancer Network (NCCN) guidelines recommend :

• Two cycles of ABVD regimen and additional ABVD cycles or ABVD with radiation therapy (RT), or
• Three cycles of Stanford V regimen for  (12 weeks) and radiation therapy (RT), or
• BEACOPP ( bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) regimen for two cycles with radiation therapy (RT)

For treatment of bulky classic Hodgkin's Lymphoma at unfavorable stage I-II, the National Comprehensive Cancer Network (NCCN) guidelines recommend:

• ABVD for four cycles and radiation therapy or
• Stanford V regimen for three cycles (12 weeks) or
• BEACOPP regimen for two cycles and ABVD for two cycles with radiation therapy

The National Comprehensive Cancer Network (NCCN) guidelines recommend ABVD for six cycles or three cycles (12 weeks) of Stanford V regimen or BEACOPP regimen for six cycles for treatment of non-bulky advanced-stage disease (at stage III-IV). For treatment of bulky advanced disease addition of radiation therapy is recommended.

For refractory or relapsed disease both the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO) guidelines recommend high-dose chemotherapy followed by autologous stem cell transplantation (ASCT).

The table below summarizes the treatment for each stage of Hodgkin's lymphoma according to the National Comprehensive Cancer Network (NCCN) guidelines:

Medical therapy for Hodgkin's lymphoma according to the National Comprehensive Cancer Network (NCCN) guidelines

Stage	Chemotherapy	Radiotherapy	Stem cell transplant
Stage I-II
Stage I-II with favorable prognosis	ABVD regimen: Adriamycin (Doxorubicin), Bleomycin, Vinblastine, Dacarbazine four cycles OR Stanford V regimen: Doxorubicin, Vinblastine, Mechlorethamine [or cyclophosphamide], Etoposide, Vincristine, Bleomycin, and prednisone for 8-week		---------
Stage I-II with unfavorable prognosis	ABVD: Adriamycin AND Bleomycin AND Vinblastine AND Dacarbazine two cycles OR Stanford V regimen Three cycles of for  12 -weeks OR BEACOPP ( bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) regimen for two cycles	20 Gy Radiation Therapy	---------
Stage III & IV
Non-bulky advanced-stage disease (at stage III-IV)	ABVD: Adriamycin AND Bleomycin AND Vinblastine AND Dacarbazine two cycles OR Stanford V regimen Three cycles of for  12 -weeks OR BEACOPP ( bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, prednisone) regimen for two cycles Brentuximab vedotin plus AVD (BV-AVD) every 2 weeks for a maximum of 12 doses		---------
	(MOPP) Mechlorethamine AND Oncovin AND Prednisone AND Procarbazine (ABVD) Adriamycin AND Bleomycin AND Vinblastine AND Dacarbazine (Stanford V) Adriamycin AND Bleomycin AND Vinblastine AND Vincristine AND Mechlorethamine AND Etoposide AND Prednisone (BEACOPP) Bleomycin AND Etoposide AND Adriamycin AND Cyclophosphamide AND Oncovin AND Procarbazine AND Prednisone	---------	---------
Recurrent disease
Recurrence	(MOPP) Mechlorethamine AND Oncovin AND Prednisone AND Procarbazine (ABVD) Adriamycin AND Bleomycin AND Vinblastine AND Dacarbazine (Stanford V) Adriamycin AND Bleomycin AND Vinblastine AND Vincristine AND Mechlorethamine AND Etoposide AND Prednisone (BEACOPP) Bleomycin AND Etoposide AND Adriamycin AND Cyclophosphamide AND Oncovin AND Procarbazine AND Prednisone (GDP) Gemcitabine AND Dexamethasone AND Cisplatin (CBV) Cyclophosphamide AND Carmustine AND Etoposide (BEAM) Carmustine AND Etoposide AND Cytarabine AND Melphalan Pembrolizumab every 3 weeks (if relapse occurred with 3 or more lines of therapy)	External beam radiation therapy may be offered	Stem cell transplant may be offered

The algorithms below summarize the treatment for each stage of Hodgkin's lymphoma according to the European Society for Medical Oncology (ESMO) guidelines:

Favorable prognosis stage I-II

ABVD x 2 Cycles

ABVD x 2 Cycles

20 Gy RT

PET-CT scan

PET-positive

PET-negative

BEACOPPesc x 2 Cycles

ABVD x 1 Cycle

30 Gy RT

20 Gy RT

Unfavorable prognosis stage I-II

ABVD x 4 Cycles OR BEACOPPesc x 2 Cycles + ABVD x 2 Cycles

ABVD x 2 Cycles

30 Gy RT

PET-CT scan

PET-positive

PET-negative

BEACOPPesc x 2 Cycles

ABVD x 2 Cycles

30 Gy RT

30 Gy RT

Advanced Stages HL

ABVD x 6 OR BEACOPPesc x 6

BEACOPPesc x 2 Cycles

ABVD x 2

RT to residual lymphoma > 2.5cm

PET-CT scan

PET-CT scan

PET-positive

PET-negative

PET-positive

PET-negative

BEACOPPesc x 4 Cycles

BEACOPPesc x 2 Cycles

ABVD x 4 Cycles OR BEACOPPesc x 4 Cycles

AVD x 4 Cycles

PET-CT

PET-CT

PET-positive

PET-negative

PET-positive

PET-negative

RT to residual lymphoma>2.5 cm

Follow up

RT to residual lymphoma>2.5 cm

Follow up

Medical therapy during pregnancy

First trimester of pregnancy

• < 32 weeks

• Watchful waiting when the cancer is above the diaphragm and is slow-growing

• > 32 weeks

• Delivery may be induced, systemic chemotherapy using one or more drugs
• Radiation therapy above the diaphragm (A lead shield is used to protect the fetus from the radiation as much as possible)

Second half of pregnancy

• < 32 weeks

• Watchful waiting, most women can delay treatment until after the baby is born

• > 32 weeks

• Systemic chemotherapy using one or more drugs
• Steroid therapy
• Radiation therapy to relieve breathing problems caused by a large tumor in the chest

Chemotherapy

• Chemotherapy may be used:

• As the primary treatment, with or without radiation therapy, to destroy cancer cells
• To treat relapsed Hodgkin's lymphoma (that comes back after treatment) or refractory Hodgkin's lymphoma (that is resistant to the initial treatment)
• To control the symptoms of advanced (palliative chemotherapy)

Radiation therapy

• Radiation may be used for Hodgkin's lymphoma (HL):

• As the primary treatment with chemotherapy to reduce the risk of recurrence
• For stage I & II Hodgkin's lymphoma, given after chemotherapy to the areas where the Hodgkin's lymphoma was initially found or before chemotherapy to shrink a large tumor. Radiation therapy may be given alone:

• If the person cannot tolerate chemotherapy because of other health issues
• If the Hodgkin's lymphoma is localized in a small area of lymph nodes
• For nodular lymphocyte predominant Hodgkin's lymphoma when no B symptoms are present

• For stage III Hodgkin's lymphoma, given after chemotherapy if the Hodgkin's lymphoma is localized in an area of the body and can be included in the radiation field
• For relapsed or primary refractory Hodgkin's lymphoma if the original treatment was chemotherapy only and the Hodgkin's lymphoma remains or returns in only a single area
• To shrink bulky tumors before chemotherapy
• Alone, in certain situations

• For early stage favorable Hodgkin's lymphoma when the person cannot tolerate chemotherapy because of other health problems
• When the Hodgkin's lymphoma is a small localized area and the lymph nodes are very small
• For early stage nodular lymphocyte predominant Hodgkin's lymphoma without B symptoms

• To control the symptoms of advanced Hodgkin's lymphoma (palliative radiation therapy)

• The dose and schedule for the radiation therapy are determined by:

• The extent of the disease
• Whether or not the radiation therapy is given with chemotherapy
• Whether the treatment is intended to be curative or palliative

External beam radiation therapy

Hodgkin's lymphoma is often treated with external beam radiation therapy. A machine directs radiation to the tumor and some of the surrounding tissue.

Radiation field

• Each person’s situation is unique, and the radiation fields may be adjusted depending on the extent of the disease. Radiation treatments are given to different areas of the body when treating Hodgkin's lymphoma. The radiation field is the part of the body that receives the radiation. Some of radiation fields to treat Hodgkin's lymphoma are:

• Involved field: only the lymph node areas with Hodgkin's lymphoma (the standard field used in combination with chemotherapy)

• Chemotherapy is given first, followed by involved field radiation to the original site of the disease

• Mantle field: lymph nodes in the neck, chest and axilla
• Upper abdominal field: lymph nodes in the upper abdomen and possibly the spleen
• Pelvic field, or Inverted (upside down) Y field: lymph nodes in the pelvis and groin
• Extended field: the mantle field and uppermost part of the inverted Y field

• This is seldom used anymore because nearly all people with Hodgkin's lymphoma are treated with chemotherapy

• Total nodal irradiation

• Is the term used when radiation is given to all fields
• Is basically a combination of the mantle and inverted Y fields
• May be used for people with widespread, advanced stage disease
• Is used when low-dose radiation is given to the entire body in preparation for a stem cell transplant

Stem cell transplantation

• Stem cell transplantation may be considered for individuals with Hodgkin's lymphoma in the following cases:

• When the Hodgkin's lymphoma is not responding to other treatments or standard treatment has failed to work (refractory disease)
• If the Hodgkin's lymphoma comes back after an initial response to treatment (relapsed disease)

References

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