What is the recommended treatment for low‑grade B‑cell non‑Hodgkin lymphoma involving the nasopharynx with splenic nodules?

Treatment of Low-Grade B-Cell Lymphoma of the Nasopharynx with Splenic Nodules

For low-grade B-cell non-Hodgkin lymphoma involving the nasopharynx with splenic involvement, you should initiate systemic therapy with rituximab plus chemotherapy (R-CHOP or similar regimen) rather than radiation alone, as the presence of splenic nodules indicates Stage III disease requiring systemic treatment. 1

Staging Determines Treatment Approach

The presence of splenic nodules is critical to your treatment decision:

• Splenic involvement automatically classifies this as Stage III disease, as the spleen is considered nodal tissue and involvement on both sides of the diaphragm (nasopharynx above, spleen below) defines Stage III. 1
• PET-CT is the gold standard for staging FDG-avid lymphomas and should be used to fully assess disease extent, though most low-grade B-cell lymphomas (except follicular lymphoma) are variably FDG-avid and may require contrast-enhanced CT. 2, 1
• For patients staged with PET-CT, focal uptake in the spleen consistent with lymphoma distribution confirms splenic involvement. 2

Systemic Therapy Is Required for Advanced-Stage Disease

Rituximab-based chemoimmunotherapy is the standard approach:

• The combination of rituximab (anti-CD20 monoclonal antibody) with CHOP chemotherapy has demonstrated a 95% overall response rate in low-grade B-cell lymphoma, with 55% complete response rates. 3
• Rituximab is FDA-approved for relapsed/refractory and previously untreated follicular CD20-positive B-cell NHL, and should be combined with first-line chemotherapy. 4
• The rituximab-CHOP combination shows additive therapeutic benefit with no significant added toxicity compared to chemotherapy alone, and can clear minimal residual disease. 3

Critical pre-treatment requirements:

• Screen all patients for hepatitis B virus (HBsAg and anti-HBc) before initiating rituximab, as HBV reactivation can result in fulminant hepatitis and death. 4
• Obtain complete blood counts with differential and platelets prior to first dose. 4
• Premedicate before each rituximab infusion to manage infusion-related reactions. 4

Radiation Therapy Has a Limited Role in Advanced Disease

While radiation is highly effective for localized disease, it is not the primary modality here:

• Radiation therapy (30-35 Gy) achieves excellent local control for Stage I-II low-grade lymphomas, with long-term control and possible cure. 5, 6
• However, approximately 50% of patients with follicular lymphoma relapse with systemic disease outside radiation fields after 15 years when treated with radiation alone for early-stage disease. 5, 6
• With Stage III disease already present (splenic involvement), systemic therapy is mandatory; radiation may be considered for symptomatic local control of the nasopharyngeal site if needed after systemic therapy. 5

Treatment Algorithm

1. Confirm diagnosis and staging:

   • Ensure CD20-positive low-grade B-cell histology
   • Complete PET-CT or contrast-enhanced CT staging 2, 1
   • Screen for HBV infection 4
   • Obtain baseline CBC 4

2. Initiate systemic therapy:

   • Rituximab 375 mg/m² per infusion with CHOP chemotherapy (typically 6 cycles) 4, 3
   • Monitor CBC weekly to monthly during treatment 4
   • Monitor for HBV reactivation during and after treatment 4

3. Consider maintenance rituximab:

   • For patients achieving complete or partial response, single-agent rituximab maintenance is FDA-approved 4

4. Reserve radiation for specific indications:

   • Symptomatic nasopharyngeal disease requiring local control
   • Residual disease after systemic therapy

Common Pitfalls to Avoid

• Do not treat with radiation alone when splenic involvement is present—this represents systemic disease requiring systemic therapy. 1, 5
• Never skip HBV screening before rituximab initiation, as reactivation can be fatal. 4
• Do not delay treatment in symptomatic patients; asymptomatic patients with indolent NHL may be observed, but the presence of nasopharyngeal involvement often indicates symptoms. 2, 7
• Avoid assuming all low-grade lymphomas are FDG-avid—chronic lymphocytic leukemia/small lymphocytic lymphoma, lymphoplasmacytic lymphoma, and marginal zone lymphomas are variably FDG-avid and may require CT staging. 2