What is the initial treatment for Non-Hodgkin lymphoma (NHL)?

Initial Treatment for Non-Hodgkin Lymphoma

For CD20-positive diffuse large B-cell lymphoma (DLBCL), the standard first-line treatment is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) given for 6-8 cycles every 21 days, which is a Category 1 recommendation. 1, 2

Treatment Selection by NHL Subtype

Diffuse Large B-Cell Lymphoma (DLBCL)

Standard Regimen:

• R-CHOP-21 (every 21 days) for 6-8 cycles is the established standard for all stages of CD20-positive DLBCL 1, 3
• Dose-dense R-CHOP-14 (every 14 days with growth factor support) is an acceptable alternative, particularly showing benefit in patients 60-81 years old 1, 4
• Eight doses of rituximab should be administered with the chemotherapy cycles 1

Alternative Regimens for Specific Situations:

• For patients with poor left ventricular function who cannot receive doxorubicin: RCEPP, RCDOP, RCNOP, or RCEOP are acceptable alternatives 1
• Dose-adjusted EPOCH-R is a Category 2B option, particularly for younger patients 1

Primary Mediastinal Large B-Cell Lymphoma (PMBL)

• R-CHOP-21 is widely used based on DLBCL data, though optimal therapy remains more controversial 1, 5
• Dose-adjusted EPOCH + rituximab is a Category 2B alternative 1, 5
• Prephase treatment with prednisone 100 mg orally daily for 5-7 days before starting R-CHOP is recommended for patients with bulky mediastinal masses to prevent tumor lysis syndrome 5
• The role of consolidative radiotherapy is controversial and should be guided by end-of-treatment PET-CT results; if PET-CT is negative, observation without radiotherapy is appropriate 1, 5

Follicular/Low-Grade NHL

• R-CHOP or R-CVP (rituximab, cyclophosphamide, vincristine, prednisone) are standard options 2, 6
• For previously untreated follicular NHL achieving complete or partial response, single-agent rituximab maintenance therapy is indicated 2
• For non-progressing low-grade NHL after first-line CVP chemotherapy, single-agent rituximab is appropriate 2

Mantle Cell Lymphoma (MCL)

For Stage II (Bulky) and Stage III-IV:

• R-CHOP or R-CVP can yield acceptable survival outcomes 1
• For younger patients (<65 years), more intensive approaches such as R-hyper-CVAD alone or rituximab-containing regimens followed by high-dose therapy with autologous stem cell rescue show superior progression-free survival compared to R-CHOP alone 1

Critical Pre-Treatment Requirements

Mandatory Baseline Assessments:

• Complete blood count, LDH, and uric acid levels 1, 5
• HIV and hepatitis B/C screening (HBsAg and anti-HBc mandatory before rituximab) 1, 3
• CT scans of chest, abdomen, and pelvis 1
• Bone marrow aspirate and biopsy 1
• Protein electrophoresis for B-cell lymphomas 1

CNS Prophylaxis Considerations:

• Diagnostic lumbar puncture with prophylactic intrathecal cytarabine and/or methotrexate should be performed in high-risk patients (>2 adverse IPI parameters), especially those with bone marrow, testis, spine, or skull base involvement 1, 7

Essential Supportive Care Measures

Tumor Lysis Syndrome Prevention:

• In patients with high tumor burden, special precautions are required to prevent tumor lysis syndrome 1
• Prephase corticosteroid treatment should be considered 7, 5

Infection Prophylaxis:

• Hepatitis B prophylaxis with entecavir for HBsAg-positive patients receiving rituximab 3
• PJP prophylaxis for bendamustine/rituximab combinations 3
• Herpes zoster prophylaxis for proteasome inhibitor-based regimens 3

Hematologic Support:

• Dose reductions due to hematological toxicity should be avoided to maintain treatment efficacy 1, 7
• Prophylactic granulocyte colony-stimulating factor (G-CSF) is justified for febrile neutropenia and is essential for dose-dense regimens 1, 7, 4

Response Evaluation Strategy

Interim Assessment:

• Repeat abnormal baseline radiological tests after 3-4 cycles to exclude disease progression 1, 5
• PET-CT is preferred for response assessment in FDG-avid lymphomas 3

End-of-Treatment Assessment:

• Repeat imaging after the last cycle of chemotherapy 1
• Bone marrow aspirate/biopsy should only be repeated at end of treatment if initially involved 1
• PET-CT is essential post-treatment, particularly for PMBL, to guide decisions about consolidative radiotherapy 1, 5
• In case of therapeutic consequences from PET positivity, histological confirmation is strongly recommended 1

Role of Consolidative Radiotherapy

• Consolidation radiotherapy to sites of bulky disease has not proven benefit in most cases 1
• May be considered for sites of initial bulky disease (>2.5 cm residual) or PET-positive residual disease after induction 3
• For PMBL, if PET-CT is negative at end of treatment, observation without radiotherapy is appropriate 1, 5

Common Pitfalls to Avoid

Dose Intensity:

• Maintaining full dose and on-schedule delivery is critical for survival outcomes in aggressive NHL 4
• Avoid dose reductions unless absolutely necessary, as this significantly compromises outcomes 1, 7, 5

Age Considerations:

• Elderly patients (≥65 years) have higher rates of cardiac adverse reactions (supraventricular arrhythmias) and serious pulmonary events (pneumonia, pneumonitis) with R-CHOP 2
• For CLL patients ≥70 years, no observed benefit from adding rituximab to fludarabine/cyclophosphamide was seen, with higher rates of Grade 3-4 neutropenia, febrile neutropenia, and infections 2

Rituximab-Specific Considerations:

• Screen for hepatitis B before initiating rituximab, as viral reactivation can occur 1, 3
• Rituximab is FDA-approved for pediatric patients ≥6 months with previously untreated advanced-stage CD20-positive DLBCL/Burkitt lymphoma/mature B-cell acute leukemia in combination with chemotherapy 2