What is the recommended first-line treatment for B cell lymphoma?

Treatment for B Cell Lymphoma

First-Line Treatment Recommendation

For diffuse large B-cell lymphoma (DLBCL), the standard first-line treatment is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) administered for 6-8 cycles every 21 days, which represents the established standard of care across all age groups. 1, 2, 3

Treatment Algorithm by Lymphoma Subtype and Patient Characteristics

Diffuse Large B-Cell Lymphoma (DLBCL)

Standard Regimen:

• Six to eight cycles of R-CHOP-21 (every 21 days) is the current standard for all patients with DLBCL 1, 2, 3, 4
• R-CHOP-14 (every 14 days) does not provide superior outcomes compared to R-CHOP-21 and should not be used as standard therapy 4
• For patients aged 60-80 years, six to eight cycles of R-CHOP plus eight doses of rituximab given every 21 days is recommended 1, 2

Age-Specific Modifications:

• For young patients (<60 years) with low-intermediate risk disease, six cycles of R-CHOP-21 with radiotherapy to sites of previous bulky disease is effective 2
• Alternatively, R-ACVBP (rituximab, doxorubicin, vindesine, cyclophosphamide, bleomycin, and prednisolone) given every 2 weeks followed by sequential consolidation has shown improved survival in young patients 2

Critical Treatment Principles:

• Administer prednisone 100 mg orally for several days as "prephase" treatment to prevent tumor lysis syndrome in patients with high tumor burden 2
• Avoid dose reductions due to hematological toxicity to maintain treatment efficacy 2, 3
• Use prophylactic hematopoietic growth factors for febrile neutropenia in patients treated with curative intent and in all elderly patients 2

Follicular Lymphoma (FL)

Initial Treatment:

• Anti-CD20 antibody-based chemoimmunotherapy is the standard initial treatment 1
• R-CHOP or other rituximab-containing regimens are appropriate first-line options 1

Relapsed/Refractory Disease:

• For relapse after first-line therapy, alternate non-cross-resistant chemoimmunotherapy regimens or combination lenalidomide plus rituximab are options 1
• After 2 prior therapies, PI3K inhibitors (idelalisib, copanlisib, or duvelisib) are recommended, with idelalisib showing 56% overall response rate and copanlisib showing 59% overall response rate 1

Cutaneous B-Cell Lymphomas

Primary Cutaneous Marginal Zone Lymphoma (PCMZL):

• Solitary/localized disease: Local radiotherapy (20-36 Gy), excision, or antibiotics (if B. burgdorferi infection documented) 1
• Multifocal disease: Wait-and-see approach, local radiotherapy, chlorambucil, or intravenous rituximab 1
• For B. burgdorferi-associated PCMZL, systemic cephalosporins are superior to oral tetracyclines, with 43% achieving complete response 1

Primary Cutaneous Large B-Cell Lymphoma, Leg Type (PCLBCL, LT):

• Solitary/localized disease: R-CHOP or involved field radiotherapy 1
• Multifocal disease: R-CHOP is the standard treatment 1

Essential Supportive Care and Monitoring

Pre-Treatment Requirements:

• Screen all patients for hepatitis B (HBsAg and anti-HBc) before initiating rituximab; administer prophylactic entecavir for HBsAg-positive patients 3, 5
• Obtain complete blood counts including platelets prior to first dose 5
• Screen for hepatitis C and HIV 6

During Treatment:

• Monitor CBC with differential and platelet counts at weekly to monthly intervals during R-CHOP plus chemotherapy 5
• Consider PJP prophylaxis for bendamustine/rituximab combinations 3
• Consider herpes zoster prophylaxis for proteasome inhibitor-based regimens 3

Infusion Precautions:

• Administer rituximab only as intravenous infusion, never as IV push or bolus 5
• Premedicate before each infusion 5
• Monitor patients closely during infusion, as approximately 80% of fatal infusion reactions occur with the first infusion 5

Response Evaluation

Timing and Methods:

• Perform response evaluation after 3-4 cycles and after completion of treatment 1, 2, 3
• PET-CT is preferred for response assessment in FDG-avid lymphomas 3, 6
• Repeat abnormal radiological tests at baseline after 3-4 cycles and after last cycle 1
• Bone marrow biopsy should be repeated only at end of treatment if initially involved 1

Consolidative Radiotherapy

• Consider consolidative radiotherapy for sites of initial bulky disease (>2.5 cm residual after chemotherapy) 3, 6
• May consider radiotherapy for PET-positive residual disease after induction chemotherapy 3
• Consolidation radiotherapy to sites of bulky disease has not proven beneficial in routine use 1

Relapsed/Refractory Disease Management

Salvage Therapy Approach:

• Histological verification should be obtained for all relapses, especially those >12 months after initial diagnosis 1, 2
• For suitable patients (adequate performance status, age <65-70 years, no major organ dysfunction), salvage regimen with rituximab and chemotherapy followed by high-dose treatment with autologous stem cell transplantation is recommended 1, 2, 3
• Acceptable salvage regimens include R-DHAP, R-ESHAP, R-ICE, or R-IMVP16 1
• Achieving negative PET should be the goal of salvage therapy 3

CAR T-Cell Therapy:

• CAR T-cell therapy has emerged as a novel treatment option for relapsed/refractory DLBCL 1

Follow-Up Schedule

Surveillance Protocol:

• History and physical examination every 3 months for first year, every 6 months for 2 more years, then annually 1, 2, 3
• Blood count and LDH at 3,6,12, and 24 months, then only as needed for evaluation of suspicious symptoms 1
• CT scans at 6,12, and 24 months after end of treatment 1
• Routine surveillance with PET scan is not recommended 1
• Monitor thyroid function if neck was irradiated 3, 6

Important Clinical Pitfalls

Common Errors to Avoid:

• Do not reduce R-CHOP doses for hematological toxicity, as this compromises efficacy 2, 3
• Do not use R-CHOP-14 instead of R-CHOP-21, as the phase III trial showed no superiority and R-CHOP-21 remains standard 4
• Do not omit hepatitis B screening before rituximab, as HBV reactivation can result in fulminant hepatitis and death 3, 5
• Do not administer rituximab as IV push or bolus; only use as IV infusion 5

Special Considerations:

• For primary CNS lymphoma, treatment must contain high-dose methotrexate, with addition of high-dose cytarabine improving outcomes 2
• Cutaneous relapses in PCMZL do not signify worse prognosis and can be treated the same as initial lesions 1
• Lenalidomide maintenance for 24 months after CR or PR to R-CHOP significantly prolongs progression-free survival in elderly DLBCL patients, though overall survival benefit remains unproven 7