Hodgkin Lymphoma (HL)

Background:

• B-cell lymphoid malignancy, characterized by Reed-Sternberg cells (resemble owl’s eyes)

• Most commonly affecting young adults

• Presenting with painless LAP and sometimes B symptoms

• Types:

  • Classic Hodgkin Lymphoma:

    • CD15+, CD30+ and CD20-

  • Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL):

    • CD15-, CD30- and CD20+

• Deaville Scoring System:

  • Used to interpret FDG-PET scans for response assessment in HL and aggressive NHLs:

    1 = No uptake

    2 = Uptake ≤ mediastinum

    3 = Uptake > mediastinum but ≤ liver

    4 = Uptake moderately higher than liver

    5 = Uptake markedly higher than liver and/or new lesions

    • Scores 1–3 are PET-negative (complete metabolic response)

    • Scores 4–5 are PET-positive (residual active disease)

Stages:

Stage IA/IIA favorable:

• Favorable disease:

  • Stage IA/IIA + non-bulky disease + no unfavorable risk factors

• Treatment:

  • ABVD x2 cycles → PET/CT

    • If Deauville 1-2:

      • Involved-site radiation therapy (ISRT)

      • ABVD x 2 additional cycles (total 4)

        • Doxorubicin (Adriamycin), Bleomycin, Vinblastine, Dacarbazine

Stage I/II unfavorable:

• Unfavorable disease:

  • Stage I/II + any of the following factors:

    • B symptoms

    • Bulky disease (mediastinal mass ratio >0.33, any mass >10 cm)

    • Extranodal involvement

    • ESR ≥50 (or ≥30 if B symptoms are present)

    • >3 nodal sites

• Treatment:

  • ABVD x2 cycles → PET/CT

    • If Deauville 1-3:

      • ABVD x2 additional cycles + ISRT

      • AVD x4 additional cycles

    • If Deauville 4-5:

      • ABVD x2 additional cycles or BrECADD → PET/CT

        • BrECADD: Brentuximab vedotin, Etoposide, Cyclophosphamide, doxorubicin (Adriamycin), Dacarbazine, Dexamethasone

        • If Deauville 1-4: ISRT 30 Gy

        • If Deauville 5: Biopsy

- If negative: ISRT 30 Gy

- If positive: Treat as primary refractory

Stage III-IV:

• International Prognostic Score (IPS) 1 point per factor:

  • Albumin <4

  • Hb <10.5

  • Male gender

  • Age ≥ 45

  • Stage IV disease

  • WBC >15000

  • Lymphocytopenia (Lymphocyte <8% of WBC and/or ALC < 600)

• Treatment:

  • AVD-Nivo x6 cycles → PET/CT

  • BrECADD + GCSF x 2 cycles (age 18-61) → PET/CT

    • Deauville 1-3: BrECADD + GCSF x 2 cycles (total 4) -> PET/CT

    • Deauville 4-5: Biopsy

      • If negative: BrECADD + GCSF x 4 cycles (total 6)

      • If positive: Treat as primary refractory disease

  • BV-AVD x6 cycles → PET/CT

    • BV-AVD: Brentuximab Vedotin, Doxorubicin (Adriamycine), Vinblastine, Dacarbazine

    • Deauville 1-3: Follow up

    • Deauville 4-5: Biopsy

      • If negative: Follow up

      • If positive: Treat as primary refractory disease

    • BV-AVD provides a significant overall survival advantage compared to ABVD (ECHELON)

    • BV-AVD causes neuropathy and neutropenia than ABVD

  • ABVD x2 cycles → PET/CT

    • Deauville 1-3: AVD x 4 cycles

    • Deauville 4-5: BrECADD + GCSF x3 cycles → PET/CT

      • Deauville 1-3: BrECADD + GCSF x1 cycle

      • Deauville 4-5: Biopsy

        • If negative: BrECADD + GCSF x1 cycle → PET/CT

        • If positive: Treat as primary refractory disease

• Surveillance:

  • H&P every 3-6 months for first 1-2 years, then every 6-12 months until year 3, then annual.

  • CT imaging (not PET) is optional, no more than q6 months in the first 2 years.

Primary Refractory Disease:

• Treatment:

  • I/O containing regimen is preferred followed by Auto-HSCT

    • BV-Nivolumab

      • BV: Brentuximab Vedotin

    • GVD-Pembro

      • GVD: Gemcitabine, Vinorelbine, Liposomal Doxorubicin

    • ICE-Nivolumab

      • ICE: Ifosfamide, Carboplatin, Etoposide

    • ICE-Pembro

  • Non I/O containing regimen

    • BV

    • BV-Bendamustine

    • DHAP: Dexamethasone, High-dose cytarabine, Cisplatin

    • GVD

    • Gem/Benda/Vinorelbine

    • ICE +/- BV

    • IGEV: Ifosfamide, Gemcitabine, Vinorelbine

  • Consider post-autoHSCT brentuximab vedotin for patients ≥2 of the following risk factors:

    • Remission duration <1 year

    • Extranodal involvement

    • PET+ response at the time of transplant

    • B symptoms

    • >1 salvage/subsequent therapy regimen

  • Third line options:

    • Bendamustine

    • Benda/Carbo/Etoposide

    • Gem/Cis/Dex

    • Everolimus

    • Lenalidomide

    • Nivolumab

    • Vinblastine

Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)

• Immunophenotype: CD15-, CD30- and CD20+

• Risk of transformation to aggressive large B-cell lymphoma

• Treatment:

  • Stage IA/IIA (non-bulky)

    • ISRT

    • Observation

      • Usually if node is completely excised

  • Stage IB/IIB or IA-IIA (bulky)

    • Chemotherapy + Rituximab + ISRT

  • Stage IIA (non-contiguous)

    • Chemotherapy + Rituximab +/- ISRT

    • Rituximab

  • Stage III/IV

    • Observation: if asymptomatic

    • Chemotherapy + Rituximab +/- ISRT

    • Rituximab

    • Local RT

• PET/CT after treatment to assess response