What are the treatment options for lymphoma?

Treatment Options for Lymphoma

Treatment for lymphoma depends critically on the specific subtype and stage: for follicular lymphoma stages I-II, radiotherapy (24-30 Gy) is the preferred curative approach, while advanced-stage follicular lymphoma requires rituximab-based immunochemotherapy (R-CHOP or R-bendamustine) followed by rituximab maintenance, and diffuse large B-cell lymphoma is treated with R-CHOP for 8 cycles regardless of stage. 1, 2, 3

Diagnostic Requirements Before Treatment

Proper diagnosis requires an excisional lymph node biopsy—never rely on fine needle aspiration or core biopsy except in emergencies requiring immediate treatment. 1, 4

• The specimen must provide adequate tissue for WHO classification, immunohistochemistry (including CD20 status), and grading 1, 4
• Complete staging workup includes: CT chest/abdomen/pelvis, bone marrow aspirate and biopsy, complete blood count, LDH, beta-2 microglobulin, and screening for HIV, hepatitis B and C 1, 4, 5
• PET-CT is mandatory for confirming limited stage I-II disease before radiotherapy 1

Treatment Algorithm by Lymphoma Type and Stage

Follicular Lymphoma (Indolent)

Limited Stage I-II (Low Tumor Burden)

• Involved-site radiotherapy (ISRT) 24-30 Gy is the treatment of choice with curative intent 1, 2, 5
• The 24 Gy dose is as effective as higher doses (40-45 Gy) with fewer side effects 5
• Consider combining ISRT with rituximab monotherapy for optimal balance between efficacy and toxicity 1
• For patients with large abdominal fields or limited life expectancy, watch-and-wait or rituximab monotherapy alone may be considered 1

Limited Stage I-II (High Tumor Burden)

• Treat as advanced stage disease with systemic immunochemotherapy 1
• High tumor burden includes: bulky disease, adverse prognostic features (FLIPI >2), or sites where ISRT is not feasible (lung, liver) 1, 2

Advanced Stage III-IV (Asymptomatic, Low Tumor Burden)

• Watch-and-wait is appropriate—no curative therapy exists, and 15-20% experience spontaneous regression 1, 2
• Initiate treatment only when symptoms develop: B symptoms, hematopoietic impairment, bulky disease, vital organ compression, ascites/pleural effusion, or rapid progression 1, 2

Advanced Stage III-IV (Symptomatic or High Tumor Burden)

• First-line: Obinutuzumab or rituximab combined with bendamustine OR CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) 1, 2, 3
• Alternative regimens include CVP or purine analogue-based schemes (fludarabine, cyclophosphamide, mitoxantrone) 1
• Rituximab maintenance every 2 months for 2 years after immunochemotherapy substantially prolongs progression-free survival and overall survival 1, 2, 5

Relapsed/Refractory Follicular Lymphoma

• For early relapse (<12-24 months): use non-cross-resistant regimen 2
• If previous rituximab-containing regimen achieved >6-12 months remission, add rituximab again 2
• For rituximab-refractory disease or remissions <6 months: obinutuzumab-bendamustine plus obinutuzumab maintenance 2
• Consider high-dose chemotherapy with autologous stem cell transplant for patients with brief first remissions after rituximab-containing regimens 2, 5
• Rituximab maintenance every 3 months for up to 2 years after relapse therapy 2

Diffuse Large B-Cell Lymphoma (Aggressive)

R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, prednisone) given every 21 days for 8 cycles is the standard treatment for CD20-positive DLBCL of all stages. 4, 3, 6

• This applies to both adult and pediatric patients (aged 6 months and older) 3
• Aggressive lymphomas are managed with curative intent due to high chemosensitivity despite rapid proliferation 7

Critical Management Principles

Hepatitis B Prophylaxis

In patients with positive hepatitis B serology (including occult carriers), prophylactic antiviral medication is mandatory up to 2 years beyond last rituximab exposure to prevent potentially fatal HBV reactivation. 2, 3

Response Monitoring

• Perform radiological tests after every 2-3 cycles of therapy and after completion of chemotherapy 1, 4
• Patients with incomplete or lacking response require early evaluation for salvage regimens 1, 4
• PET-CT after completion of induction identifies patients with adverse prognosis, though therapeutic implications remain undefined 2

Relapse Surveillance

• At suspected relapse or progression, obtain a new confirmatory biopsy to rule out transformation 2
• History and physical examination every 3 months for 2 years, every 6 months for 3 additional years, then annually 1, 4, 5
• Monitor for transformation to aggressive lymphoma and secondary malignancies including leukemia 1, 4
• Blood count and LDH at 3,6,12, and 24 months, then as needed 4, 5
• Imaging surveillance at 6,12, and 24 months after treatment completion 1, 4, 5

Common Pitfalls to Avoid

• Never use fine needle aspiration or core biopsy for initial diagnosis—inadequate tissue prevents proper subtyping and can lead to incorrect treatment 1, 4
• Do not treat asymptomatic, low tumor burden advanced follicular lymphoma—watch-and-wait is appropriate given lack of curative therapy and potential for spontaneous regression 1, 2
• Never administer rituximab as IV push or bolus—only as infusion with appropriate medical support for severe infusion reactions 3
• Do not forget HBV screening before rituximab—reactivation can cause fulminant hepatitis and death 3
• Follicular lymphoma grade 3B (sheets of blasts) is treated as aggressive lymphoma, not indolent disease 1