What are the treatment options for follicular lymphoma?

Treatment Options for Follicular Lymphoma

The optimal treatment approach for follicular lymphoma depends on disease stage and tumor burden, with watch-and-wait being the standard approach for asymptomatic advanced cases, while symptomatic patients should receive obinutuzumab or rituximab combined with chemotherapy such as bendamustine or CHOP. 1

Initial Assessment and Staging

• Diagnosis requires a surgical specimen/excisional lymph node biopsy (fine needle aspirations are inappropriate) 1, 2
• Complete staging workup should include:
  • CT scan of thorax, abdomen, and pelvis
  • Bone marrow aspirate and biopsy
  • Complete blood count, LDH, uric acid, hepatitis B/C and HIV testing 1
• PET-CT is recommended for accurate staging and evaluating response to treatment 2
• Ann Arbor staging system is used, with the Follicular Lymphoma International Prognostic Index (FLIPI) for risk stratification 1, 2

Treatment Algorithm Based on Stage and Tumor Burden

Early Stage Disease (Stage I-II, 15-20% of patients)

• Radiotherapy is the treatment of choice with curative potential 1, 2
  • Extended field irradiation (30-40 Gy) should be performed 1, 2
  • In selected patients with large tumor burden, systemic therapy may be used 1

Advanced Stage Disease (Stage III-IV)

Asymptomatic/Low Tumor Burden

• Watch-and-wait approach is the standard 1, 2

  • This approach has been validated even in the rituximab era 3, 4
  • No survival benefit has been demonstrated with immediate treatment 4

• Rituximab monotherapy is an alternative option 1, 2

  • Can delay need for chemotherapy compared to watch-and-wait 3
  • Consider for patients concerned about disease progression 4

Symptomatic/High Tumor Burden

• Treatment indications: B symptoms, hematopoietic impairment, bulky disease, vital organ compression, ascites, pleural effusion, or rapid lymphoma progression 1

• First-line therapy options:

  • Obinutuzumab or rituximab + bendamustine - preferred if complete remission and long PFS are goals 1, 2
  • Obinutuzumab or rituximab + CHOP - preferred for more aggressive clinical course 1, 2
  • Rituximab + CVP - alternative option 2
  • Rituximab maintenance every 2 months for 2 years after immunochemotherapy 1

Management of Relapsed Disease

• Confirmatory biopsy is strongly recommended at suspected relapse 1

• Treatment options based on timing of relapse:

  • Early relapse (<12-24 months):

    • Non-cross-resistant regimen
    • Obinutuzumab-bendamustine followed by obinutuzumab maintenance for rituximab-refractory cases 1
    • High-dose chemotherapy with autologous stem cell transplantation (ASCT) for brief first remissions 1

  • Later relapses:

    • Non-chemotherapy approach preferred: lenalidomide plus rituximab 1
    • Rituximab monotherapy for symptomatic cases with low tumor burden 1
    • Radioimmunotherapy for elderly patients with comorbidities 1
    • Idelalisib for double-refractory cases (with anti-infectious prophylaxis) 1

Special Considerations

• Hepatitis B carriers: Prophylactic antiviral medication up to 2 years beyond last rituximab exposure 1, 2
• Bendamustine regimens: Extended anti-infectious prophylaxis should be considered 1
• Response evaluation: Imaging mid-treatment and after completion of chemotherapy 1
• PET-CT: Recommended after completion of induction chemotherapy for prognostic assessment 1

Follow-up Schedule

• Physical examination every 3 months for 2 years, every 6 months for 3 more years, then annually 1, 2
• Blood counts at 3,6,12, and 24 months, then as needed 1
• Imaging at 6,12, and 24 months after treatment 1
• Thyroid function evaluation at 1,2, and 5 years for patients who received neck irradiation 1

Common Pitfalls to Avoid

• Using fine-needle aspiration for initial diagnosis instead of excisional biopsy 1, 2
• Initiating treatment in asymptomatic patients with advanced disease without clear indications 1
• Failing to screen for hepatitis B before rituximab therapy 1, 2
• Not providing anti-infectious prophylaxis with bendamustine-containing regimens 1
• Overlooking the possibility of histologic transformation in patients with aggressive clinical course 2