Hodgkin Lymphoma Treatment Protocols 

Updated: Mar 17, 2017
  • Author: Francisco J Hernandez-Ilizaliturri, MD; Chief Editor: Koyamangalath Krishnan, MD, FRCP, FACP  more...
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Hodgkin Lymphoma Treatment Protocols

Treatment protocols for classical Hodgkin lymphoma (HL) are provided below, including treatment for early-stage, advanced-stage, and relapsed/refractory disease.

General guidelines follow. Check specific guidelines for restaging and dosage adjustments for chemotherapy and/or radiation therapy depending on positron-emission tomography (PET) scanning throughout the various regimens.

Management of patients with early-stage favorable HL

Stages IA-IIA:

Regimens that combine chemotherapy and radiation therapy (RT) have replaced RT alone for treatment of early-stage, favorable disease. Involved site radiation therapy (ISRT) is typically recommended, as high-dose, large-field radiation therapy (LFRT) increases risk for heart disease, pulmonary dysfunction, and secondary cancers.

Stage IA-IIA disease can be treated with the ABVD regimen for up to six cycles, or with the Stanford regimen for two cycles (ie, 8 weeks)

ABVD regimen

  • The ABVD regimen includes doxorubicin [Adriamycin], bleomycin, vinblastine, and dacarbazine) [1]
  • Combined modality consisting of doxorubicin 25 mg/m 2 IV plus  bleomycin 10 units/m 2 IV plus  vinblastine 6 mg/m 2 IV plus  dacarbazine 375 mg/m 2 IV on days 1 and 15; every 28 d generally for two to four cycles; followed by ISRT at a dose of 20-30 Gy (depends on German Hodgkin Study Group [GHSG] criteria)
  • Patients with fewer than two disease sites can be safely treated with two cycles of ABVD followed by ISRT; other patients with early-stage favorable HL should receive 4 cycles [2]
  • Imaging studies demonstrating response should be performed before proceeding with radiation therapy
  • Changes in therapy due to lack of efficacy must be supported by biopsy results documenting refractory/relapsed disease
  • Administer systemic chemotherapy with ABVD for six cycles in selected patients with early-response disease confirmed by functional imaging [3]

Stanford V regimen

The Stanford V regimen includes doxorubicin, vinblastine, mechlorethamine, etoposide, vincristine, bleomycin, and prednisone given in a 28-day cycle, as follows:

  • Day 1: mechlorethamine 6 mg/m 2 IV on day 1 plus
  • Days 1 and 15: doxorubicin 25 mg/m2 IV and vinblastine 6 mg/m2 IV plus
  • Days 8 and 22: bleomycin 5 units/m 2 IV and vincristine 1.4 mg/m 2 IV (not to exceed 2 mg/dose) plus
  • Days 15 and 16: etoposide 60 mg/m 2 IV plus
  • Prednisone 40 mg/m 2 PO every other day during weeks 1-6 (taper during weeks 7 and 8)
  • Follow with ISRT 30 Gy within 3 weeks of chemotherapy completion

Management of patients with early-stage, unfavorable, nonbulky/bulky HL

Stages I-II:

Unfavorable, bulky disease: ABVD regimen for four cycles followed by ISRT or Stanford V regimen for three cycles (12 weeks) + ISRT or escalated BEACOPP for two cycles + ABVD for two cycles +ISRT

Unfavorable, nonbulky disease: ABVD regimen for two cycles (initially with staging and additional ABVD cycles as warranted) or Stanford V regimen or escalated BEACOPPfor two cycles + ABVD for two cycles +ISRT

ABVD regimen:

  • Combined modality consisting of doxorubicin 25 mg/m 2 IV plus  bleomycin 10 IU/m 2 IV plus  vinblastine 6 mg/m 2 IV plus  dacarbazine 375 mg/m 2 IV on days 1 and 15; every 28 d for two cycles (for nonbulky disease) or four cycles (bulky) +/1 ISRT 30 Gy or systemic chemotherapy with ABVD for six cycles [1, 4]
  • ISRT at 30 Gy should be strongly considered for patients with bulky disease or those exhibiting a slow response to therapy, as confirmed by functional imaging with PET (ie, patients with PET scan–avid disease after four cycles of ABVD)
  • Changes in therapy due to lack of efficacy must be supported by biopsy results documenting proven refractory/relapsed disease

Stanford V regimen:

The Stanford V regimen includes doxorubicin, vinblastine, mechlorethamine, etoposide, vincristine, bleomycin, and prednisone given in a 28-day cycle, as follows [5] :

  • Day 1: mechlorethamine 6 mg/m 2 IV on day 1 plus
  • Days 1 and 15: doxorubicin 25 mg/m 2 IV and vinblastine 6 mg/m 2 IV plus
  • Days 8 and 22: bleomycin 5 units/m 2 IV and vincristine 1.4 mg/m 2 IV (not to exceed 2 mg/dose) plus
  • Days 15 and 16: etoposide 60 mg/m 2 IV plus
  • Prednisone 40 mg/m 2 PO every other day during weeks 1-10 (taper during weeks 11 and 12)
  • Follow within 3 weeks with ISRT 36 Gy in patients with stage 1-2 bulky mediastinal disease or bulky disease >10 cm; for nonbulky disease, use ISRT 30-36 Gy based upon presence of B symptoms

Escalated BEACOPP:

Escalated BEACOPP includes bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone in a combined-modality 21-day cycle consisting of the following:

  • Day 1: cyclophosphamide 1,200 mg/m 2 PO plus doxorubicin 35 mg/m 2 IV plus
  • Days 1-3: etoposide 200 mg/m 2 IV plus
  • Days 1-7: procarbazine 100 mg/m 2 PO plus
  • Days 1-14: prednisone 40 mg PO plus
  • Day 8: vincristine 1.4 mg/m 2 IV (not to exceed 2 mg/dose) plus bleomycin 10 mg/m 2 IV, follow by
  • Two 28-day cycles of ABVD and then ISRT

Management of patients with advanced-stage HL

Stages III-IV:

  • Systemic chemotherapy with ABVD for up to six cycles +/- ISRT [6] OR
  • Stanford V for three cycles (12 weeks) if International Prognostic Score (IPS) < 3, +/- ISRT
  • Patients with advanced HL and IPS ≥4 should be treated with dose-escalated BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) for four cycles, followed by either four standard doses of BEACOPP (bleomycin 10 units/m 2 IV on day 8 plus  etoposide 100 mg/m 2 IV on days 1-3 plus  doxorubicin 25 mg/m 2 IV on day 1 plus  cyclophosphamide 650 mg/m 2 IV on day 1 plus  vincristine 1.4 mg/m 2 IV [not to exceed 2 mg/dose] on day 8 plus  procarbazine 100 mg/m 2 PO on days 1-7 plus  prednisone 40 mg/m 2 PO on days 1-14; every 21 d) if early responders [7] or
  • If slow responders: Administer four additional dose-escalated BEACOPP (bleomycin 10 units/m 2 IV on day 8 plus  etoposide 200 mg/m 2 IV on days 1-3 plus  doxorubicin 35 mg/m 2 IV on day 1 plus  cyclophosphamide 1200 mg/m 2 IV on day 1 plus  vincristine 1.4 mg/m 2 IV [not to exceed 2 mg/dose] on day 8 plus  procarbazine 100 mg/m 2 PO on days 1-7 plus  prednisone 40 mg/m 2 PO on days 1-14; every 21d) [7]
  • ISRT should be strongly considered following any of the above chemotherapy regimens for patients with bulky disease or those exhibiting a slow response to therapy by functional imaging (PET scan)
  • Changes in therapy due to lack of efficacy must be supported by biopsy results documenting refractory/relapsed disease

Treatment recommendations for relapsed/refractory HL disease

See the list below:

  • It has been estimated that approximately 20-30% of patients with HL do not achieve a long-term remission with front-line chemotherapy
  • Salvage therapy followed by high-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT) can cure approximately 50% of patients (see below) [8]
  • Based on the British Columbia data, the best timing for HDC-ASCT is after the first relapse [9]

Regimens for patients eligible for HDC-ASCT (treatment goal = cure):

  • A vast number of regimens are used in the treatment of patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL); these are primarily based on chemotherapy agents non–cross-resistant to those used in the front-line setting, with or without rituximab
  • The goal of salvage regimens is to achieve maximum tumor burden cytoreduction in preparation for HDC-ASCT [10]
  • ICE regimen (ifosfamide, carboplatin, and etoposide) [11] : Ifosfamide 5 g/m 2 IV on day 2 plus  carboplatin area under the curve (AUC) 5 (not to exceed 800 mg/dose) on day 1 plus  etoposide 100 mg/m 2 IV daily on days 1-3; every 14 d for two cycles (see the Carboplatin AUC Dose Calculation [Calvert formula] calculator)
  • DHAP regimen (high-dose cytarabine [Ara-C], cisplatin, and dexamethasone) [12] : Dexamethasone 40 mg on days 1-4 plus  cytarabine at 2 g/m 2 IV every 12 h for two doses on day 2, plus  cisplatin 100 mg/m 2 IV on day 1; every 21 days for two cycles
  • ESHAP regimen (etoposide, methylprednisolone, Ara-C, and cisplatin) [13] : Etoposide 40 mg/m 2/day IV plus  methylprednisolone 500 mg/day IV plus  cisplatin at 25 mg/m 2/day continuous IV infusion for 4 d plus  cytarabine 2 g/m 2 on day 5; every 21-28 d for three cycles (transplant candidate)

Regimens for patients who are not eligible for HDC-ASCT or patients who have relapsed/refractory disease after HDC-ASCT:

Second-line therapies [14]

  • Unfortunately, those patients who are not eligible for HDC-ASCT or in whom HDC-ASCT failed remain a challenge for the treating oncologist, pointing to the need for novel therapeutic strategies
  • Brentuximab vedotin [15, 16] : 1.8 mg/kg IV infused over 30 min every 3 wk; continue treatment until a maximum of 16 cycles, disease progression, or unacceptable toxicity
  • Nivolumab is indicated for classic Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous HSCT and post-transplantation brentuximab vedotin [17, 18]
  • Nivolumab dosage is 3 mg/kg IV infused over 1 hr q2wk until disease progression or unacceptable toxicity
  • Pembrolizumab is indicated for adult and pediatric patients with refractory cHL or who have relapsed after 3 or more prior lines of therapy [19]
  • Pembrolizumab dosage is 200 mg IV q3wk until disease progression or unacceptable toxicity (for up to 24 months)
  • Everolimus 10 mg PO once daily
  • C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone): cyclophosphamide 650 mg/m 2 plus vincristine 1.4 mg/m 2 (not to exceed 2 mg/dose) on day 1 plus procarbazine 100 mg/m 2/day PO on days 1-7 plus prednisone 40 mg/m 2/day PO on days 1-14; every 28 d
  • ESHAP regimen (etoposide, methylprednisolone, Ara-C, and cisplatin) [13] : Etoposide 40 mg/m 2/day IV plus methylprednisolone 500 mg/day IV plus cisplatin 25 mg/m 2/day continuous IV infusion on days 1-4 plus cytarabine 2 g/m 2 on day 5; every 21-28 d for six cycles (nontransplant candidate)
  • GCD (Gemcitabine, carboplatin, dexamethasone): gemcitabine 1000 mg/m 2 IV on days 1 and 8 plus carboplatin AUC 5 IV on day 1 plus dexamethasone 40 mg/day PO on days 1-4
  • GVD (gemcitabine, vinorelbine, liposomal doxorubicin): vinorelbine 20 mg/m 2 IV plus gemcitabine 1000 mg/m 2 IV plus doxorubicin liposomal 15 mg/m 2 IV on days 1 and 8; every 21d for 2-6 cycles
  • IGEV (ifosfamide, gemcitabine, vinorelbine): 2000 mg/m 2 IV plus mesna 2600 mg/m 2 IV plus gemcitabine 800 mg/m 2 on days 1-4 plus vinorelbine 20 mg/m 2 on day 1
  • Mini-BEAM (carmustine, cytarabine, etoposide, melphalan): carmustine 60 mg/m 2 on day 1 plus etoposide 75 mg/m 2/day IV plus cytarabine 100 mg/m 2 q12h on days 2-5 plus melphalan 30 mg/m 2 IV on day 6; every 4-6 weeks
  • MINE (etoposide, ifosfamide, mesna, mitoxantrone): ifosfamide 1.33 g/m 2/day IV plus mesna 1.33 g/m 2/day IV (with ifosfamide), then mesna 500 mg PO 4 hr after each ifosfamide dose plus etoposide 65 mg/m 2/day IV on days 1-3 plus mitoxantrone 8 mg/m 2 IV on day 1
  • Histone deacetylase inhibitors, [20] immunomodulatory drugs, and adoptive cell transfer are therapeutic strategies with promising antitumor activity in heavily pretreated patients with HL
  • Referral of patients with relapsed/refractory HL is mandatory to further improve the clinical outcome of such patients.

Third-line therapies [14]

  • Bendamustine in patients who have failed HDT/ASCR or at least 2 prior multiagent chemotherapy regimens: 120 mg/m2 on days 1-2; every 28d for up to 6 cycles
  • Lenalidomide: 25 mg PO once daily on days 1-21; every 28d