Lymphoma Notes

Overview of Lymphoma

  • Lymphomas are cancers of the immune system.

  • Characterized by mutation of lymphocytes leading to enlarged lymph nodes through growth and reproduction (lymphadenopathy) and accumulation in extra-nodal tissues (bone marrow, liver, skin, brain, gut).

  • circulate in the blood and bone marrow. Move through the lymphatic system. pts usually develop lump.

Types of Lymphoma

Main Subtypes

  • Hodgkin Lymphoma (HL)

    • Classical Hodgkin Lymphoma

    • Nodular lymphocyte predominant Hodgkin Lymphoma (NLPHL)

  • Non-Hodgkin Lymphoma (NHL)

  • most common type of lymphoma

    • Subdivided into B-cell and T-cell types:

    • High-grade (aggressive):

      • Burkitt lymphoma

      • Diffuse large B-cell lymphoma (DLBCL)

      • Lymphoblastic lymphoma (B or T cell)

      • Anaplastic large cell lymphoma

    • Low-grade (indolent):

      • Follicular lymphoma

      • Marginal Zone lymphoma

      • Waldenstrom’s macroglobulinaemia

      • Small lymphocytic lymphoma

      • Mantle cell lymphoma

Epidemiology

  • Hodgkin lymphoma: ~2200 new cases annually in the UK

  • Non-Hodgkin lymphoma: ~13,600 new cases/year, 4% of new cancer cases

  • More common in males and older populations:

    • ~37% of NHL cases diagnosed in individuals over 75

  • Mortality:

    • ~4900 deaths from NHL in the UK, it is the 11th leading cause of cancer death

    • Most common type of NHL: DLBCL (30-40% of cases)

Signs and Symptoms

  • Swollen lymph nodes: Usually painless, can occur in the neck, chest, armpits, abdomen, groin.

  • B symptoms:

    • Fever

    • Drenching night sweats

    • Weight loss >10% in 6 months

  • Persistent fatigue (could be due to anaemia caused by lymphoma), cough, and shortness of breath due to enlarged lymph nodes in the chest.

  • Abdominal pain or fullness due to enlarged spleen.

  • Bruising and bleeding can occur due to too few platelets.

Diagnosis and Investigations

  • Initial assessment: clinical evaluation (performance status, presence of B symptoms, examination w/ attention to nodal areas).

  • Blood tests and imaging:

    • Chest X-ray, CT scans of neck/chest/abdomen/pelvis, echocardiogram.

    • FBC, biochem, viral tests

  • Biopsy: Lymph node excision biopsy recommended when possible.

  • Cerebrospinal fluid examination if CNS signs/symptoms are present.

Lymphoma Classification (Ann Arbor Staging)

  • Stage 1: Lymphoma in only 1 group of lymph nodes.

  • Stage 2: Lymphoma in more than one group of lymph nodes all on the same side of the diaphragm.

  • Stage 3: Lymphoma in more than one group of lymph nodes on both sides of the diaphragm.

  • Stage 4: Lymphoma in organs outside lymph nodes or spleen.

  • Staging considerations:

    • B: presence of B symptoms

    • A: absence of B symptoms

    • E: spread to other organs

    • X: bulky disease (node >10 cm)

    • S: spread to spleen

  • letters are associated with stages.

Diffuse Large B-Cell Lymphoma (DLBCL) Prognosis

  • Prognosis varies based on age, stage, health, and treatment response.

  • Many patients can be cured.

  • Some patients relapse, prognosis can be poor in relapse cases.

  • Earlier caught= better prognosis.

DLBCL Treatment

  • Standard care: 6 cycles of R-CHOP (21-day cycles)

    • R-CHOP components:

    • R: Rituximab

    • C: Cyclophosphamide

    • H: Doxorubicin (hydroxydaunomycin) - echocardiogram before treatment as can be cardiotoxic.

    • O: Vincristine (Oncovin)

    • P: Prednisolone

  • Supportive care includes:

    • Allopurino- prevent chemolysis , omeprazole- gastro, ondansetron- anti emetic, aciclovir- hsv prophylaxis , fluconazole- antifungal proph etc.

    • Filgrastim promotes neutral cell recovery- goven for 5d, give neutrophils time to recover before next cycle

  • IPI score= International Prognostic Index score which helps to assess prognosis and guide therapy decisions in lymphoma patients.

  • CNS prophylaxis: Intrathecal methotrexate.

Different MOAs depending on different stages of cell cycle targeting.

Common SE- hair loss, diarrhoea, constipation, immunosuppression etc etc

Rituximab- mAb- targets CD20 found on the surface of B cells.

Once bound, activates immune system to destroy b cells via antibody dependent cellular toxicity/ complement dependent toxiciity

  • Emerging therapies:

    • Epcoritamab: T-cell engaging bispecific antibody for relapsed/refractory DLBCL (diffuse large B cell lymphoma) after 2 or more systemic treatments

    • T cell engaging drug- bispecific antibody- binds to CD3 receptor on T cell, and CD20 receptor om surface of lymphoma and healthy B cells—> cytokine release and cell lysis.

    • Glofitamab: Similar to Epcoritamab, targets CD3 and CD20. bispecific antibody

Hodgkin Lymphoma Treatment

  • 1st line treatment: ABVD (28-day cycle)

    • A: Doxorubicin (Adriamycin)

    • B: Bleomycin

    • V: Vinblastine

    • D: Dacarbazine

  • All diff classes of cytotoxics as target diff stages in cell cycle.

  • Initial treatment of 2 cycles ABVD followed by PET scan. If this shows response, depending on grading will recieve further 4 cycles.

Emerging Therapies in Hodgkin Lymphoma

  • Brentuximab: Antibody-drug conjugate targeting CD30 on surface of cancer cells in Hodgkin lymphoma. If not suitable for transplantation.

  • Pembrolizumab: PD-1 inhibitor for relapsed/refractory Hodgkin lymphoma, enhances T-cell recognition of cancer cells.

  • Checkpoint inhibitor

  • PDL 1 is on surface of t cells, cancer cells use this and bind to, so they can hide from the immune system - PD1 inhibs block this, so cancer cells can’t hide from immune system.

Checkpoint inhibs can trigger an immune response that can lead to redness, swelling, pain and inflammation - so more specific set of toxicities associated w immunotherapies.