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

First-Line Treatment for Diffuse Large B-Cell Lymphoma

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) given every 21 days is the standard first-line treatment for CD20-positive diffuse large B-cell lymphoma, with the number of cycles and use of radiotherapy determined by patient age and risk stratification. 1, 2, 3

Treatment Algorithm by Age and Risk Category

Young Patients (Age <60 Years)

Low-Intermediate Risk (aaIPI ≤1):

• Administer six cycles of R-CHOP-21 plus radiotherapy to sites of bulky disease (30-40 Gy) 1, 2
• Alternative option: R-ACVBP (rituximab, doxorubicin, vindesine, cyclophosphamide, bleomycin, and prednisolone) given every 2 weeks followed by sequential consolidation, which has demonstrated superior survival compared to eight cycles of R-CHOP 1, 2

High/High-Intermediate Risk (aaIPI ≥2):

• Administer six to eight cycles of R-CHOP-21 1, 2
• These patients should preferably be enrolled in clinical trials given the lack of established optimal therapy 1, 2
• Do NOT use dose-dense R-CHOP-14, as it has NOT demonstrated survival benefit over R-CHOP-21 1, 4

Patients Aged 60-80 Years

• Eight cycles of R-CHOP-21 is the established standard regardless of risk category 1, 2
• R-CHOP-14 showed no survival advantage over R-CHOP-21 in this age group 1, 4
• If R-CHOP-14 is used for any reason, six cycles with eight total rituximab doses are sufficient 1
• Consolidation radiotherapy provides no proven benefit in localized disease for patients treated in the rituximab era 1

Elderly Patients (Age >80 Years)

• Comprehensive geriatric assessment is mandatory to guide treatment intensity 1
• R-CHOP can typically be used in healthy patients up to age 80 1
• R-miniCHOP (attenuated chemotherapy with rituximab) can achieve complete remission and long survival in healthy patients over 80 1
• Consider doxorubicin substitution with etoposide or liposomal doxorubicin, or omission entirely, in patients with cardiac dysfunction 1

Critical Pre-Treatment Measures

Tumor Lysis Syndrome Prevention:

• Administer prednisone 100 mg orally for several days as "prephase" treatment in patients with high tumor burden 1, 2
• Ensure adequate hydration and consider prophylactic allopurinol or rasburicase in highest-risk patients 1

Dose Intensity Maintenance:

• Avoid dose reductions due to hematological toxicity to maintain treatment efficacy 1, 2
• Prophylactic granulocyte colony-stimulating factor is indicated for febrile neutropenia in patients treated with curative intent and in all elderly patients 1, 2

CNS Prophylaxis

• CNS prophylaxis is recommended for patients with high-intermediate and high-risk IPI, particularly those with >1 extranodal site or elevated LDH 1
• Intravenous high-dose methotrexate is likely superior to intrathecal methotrexate alone 1
• Testicular lymphoma mandates CNS prophylaxis with contralateral testis irradiation 1

Special DLBCL Subtypes

Primary CNS DLBCL:

• Treatment must contain high-dose methotrexate 1, 2
• Addition of high-dose cytarabine improves complete remission rates and outcomes 1, 2

Primary Testicular DLBCL:

• Standard treatment is R-CHOP-21 with CNS prophylaxis and contralateral testis irradiation for stage I-II disease 1

Common Pitfalls to Avoid

• Do NOT use R-CHOP-14 based on outdated pre-rituximab era data; it provides no survival benefit over R-CHOP-21 in the rituximab era 1, 4
• Do NOT reduce chemotherapy doses after prephase treatment due to hematological concerns unless absolutely necessary, as this compromises efficacy 1, 2
• Do NOT omit CNS prophylaxis in high-risk patients, particularly those with testicular involvement 1
• Do NOT skip comprehensive geriatric assessment in patients over 80 years before committing to full-dose therapy 1

FDA-Approved Indication

Rituximab is FDA-approved for previously untreated diffuse large B-cell, CD20-positive NHL in combination with CHOP or other anthracycline-based chemotherapy regimens 3