What are the treatment strategies for different variants of Non-Hodgkin's (NHL) lymphoma?

Treatment Strategies for Different Variants of Non-Hodgkin's Lymphoma

Treatment of non-Hodgkin's lymphoma (NHL) must be tailored to the specific subtype, with rituximab-based regimens forming the backbone of therapy for most B-cell lymphomas.

Classification and Diagnosis

NHL comprises a heterogeneous group of lymphoproliferative disorders primarily originating from B lymphocytes (80-85%) or T lymphocytes (15-20%), with rare NK-cell variants 1. Proper diagnosis requires:

• Surgical specimen/excisional lymph node biopsy with adequate tissue for formalin-fixed samples 2
• Immunohistochemistry with minimal antibody panel (CD45, CD20, CD3) 2
• Optional determination of CD10, BCL-2, and MUM1 expression to differentiate germinal center (GCB) or activated B-cell (ABC) subtypes 2

Staging and Risk Assessment

Proper staging is essential for treatment planning:

• CT scan of chest and abdomen 2
• Bone marrow aspirate and biopsy 2
• PET/CT for better disease delineation and future response evaluation 2
• Ann Arbor staging system with mention of bulky disease 2
• International Prognostic Index (IPI) calculation 2

Treatment Approaches by NHL Subtype

Diffuse Large B-Cell Lymphoma (DLBCL)

First-line treatment:

• Young patients (≤60 years) with low-risk disease (aaIPI ≤1): 6-8 cycles of R-CHOP (rituximab 375 mg/m² plus cyclophosphamide, doxorubicin, vincristine, and prednisone) given every 21 days 2
• Young high-risk patients (aaIPI ≥2): 6-8 cycles of R-CHOP given every 14-21 days; consider clinical trials 2
• Elderly patients (>60 years): 8 cycles of R-CHOP given every 21 days or 6 cycles of R-CHOP-14 (given every 14 days) 2

Relapsed/refractory disease:

• Patients <65 years: Salvage chemotherapy (R-DHAP, R-ICE, R-ESHAP) followed by high-dose therapy with stem cell support in responsive patients 2
• Patients ≥65 years or unfit for high-dose therapy: Conventional salvage regimens (R-GEMOX) or clinical trials 2

Follicular Lymphoma (FL)

First-line treatment:

• Limited stage: Radiation therapy with or without systemic therapy 1
• Advanced stage: Rituximab-based chemoimmunotherapy (R-CHOP, bendamustine-rituximab) 1
• Maintenance: Rituximab every 2-3 months for 2 years following initial response 1

Relapsed/refractory disease:

• Rituximab monotherapy (375 mg/m² weekly for 4 weeks) 2
• Bendamustine-rituximab 1, 3
• Radioimmunotherapy with 90Y-ibritumomab tiuxetan (Zevalin) 2

Mantle Cell Lymphoma (MCL)

First-line treatment:

• Rituximab-based chemoimmunotherapy followed by high-dose therapy and autologous stem cell rescue (HDT/ASCR) for transplant-eligible patients 2
• Induction therapy followed by rituximab maintenance for non-transplant candidates 2

Relapsed/refractory disease:

• Ibrutinib (Bruton tyrosine kinase inhibitor) 2
• Bendamustine-rituximab 3

Special Populations

Pediatric NHL

• For pediatric patients aged 6 months and older with mature B-cell NHL:
  • Previously untreated, advanced stage, CD20-positive DLBCL, Burkitt lymphoma, Burkitt-like lymphoma or mature B-cell acute leukemia: Rituximab in combination with chemotherapy 4
  • Patients younger than 3 years have higher infection risk 4

Elderly Patients

• Comprehensive geriatric assessment recommended 1
• Consider R-miniCHOP (attenuated doses) for patients >80 years 1
• Monitor for increased risk of:
  • Cardiac adverse reactions (especially supraventricular arrhythmias) 4
  • Serious pulmonary adverse reactions 4
  • Neutropenia, febrile neutropenia, anemia, thrombocytopenia, and infections 4

Response Assessment and Follow-up

• PET/CT scan after 3-4 cycles and at the end of treatment 1
• Follow-up schedule:
  • Every 3 months for 1-2 years
  • Every 6 months for 2-3 more years
  • Then annually 1
• Blood count and LDH at 3,6,12, and 24 months 1
• Thyroid function evaluation if neck was irradiated at 1,2, and 5 years 2
• Women who received chest irradiation at premenopausal age should be screened for secondary breast cancers 2

Common Pitfalls and Considerations

1. CD20 status determination is crucial before starting rituximab-based therapy, as rituximab is only effective in CD20-positive lymphomas 4

2. Hepatitis B screening should be performed before rituximab therapy due to risk of HBV reactivation 4

3. Infusion-related reactions occur in the majority of patients receiving rituximab; most are mild to moderate but approximately 10% may develop severe reactions 4

4. Dose reductions due to hematological toxicity should be avoided in curative settings; consider growth factor support instead 2

5. Central nervous system prophylaxis should be considered in high-risk patients, especially with involvement of bone marrow, testis, spine, or base of skull 2

6. Early progression within 24 months of diagnosis in FL is associated with poor survival (5-year OS rate of 50% vs 90%) 1

By following these evidence-based treatment strategies tailored to specific NHL subtypes, clinicians can optimize outcomes for patients with these heterogeneous malignancies.