What is the recommended initial treatment for aggressive large B cell lymphoma?

Initial Treatment for Aggressive Large B-Cell Lymphoma

The standard initial treatment for aggressive large B-cell lymphoma is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), with specific regimens tailored based on patient age and risk factors. 1, 2

Treatment Approach Based on Patient Age and Risk

Young Patients (≤60 years)

• For young low-risk patients (age-adapted IPI ≤1), six to eight cycles of R-CHOP combined with eight doses of rituximab given every 21 days is the standard treatment 1, 2
• For young high-risk patients (age-adapted IPI ≥2), six to eight cycles of R-CHOP combined with eight doses of rituximab given every 14-21 days is recommended, though this population should ideally be treated in clinical trials 1
• For young patients with favorable prognosis, four cycles of R-CHOP plus two additional doses of rituximab has been shown to be non-inferior to six cycles of R-CHOP, with reduced toxicity 3

Patients Aged 60-80 Years

• Eight cycles of R-CHOP combined with eight doses of rituximab given every 21 days is the standard treatment 1
• If R-CHOP is given every 14 days (dose-dense approach), six cycles of CHOP with eight cycles of rituximab are sufficient 1
• Consolidation by radiotherapy to sites of previous bulky disease has not proven beneficial in this population 1

Patients Aged >80 Years

• R-CHOP can be used in fit patients up to 80 years of age 1
• For very elderly patients, rituximab with attenuated chemotherapy can induce complete remission and long survival 1

Special Considerations

CNS Prophylaxis

• CNS prophylaxis should be recommended for patients with high-intermediate and high-risk IPI, especially those with more than one extranodal site or elevated LDH 1
• Testicular lymphoma must receive CNS prophylaxis 1
• Intrathecal methotrexate is not considered an optimal method for CNS prophylaxis 1

Special Subtypes of DLBCL

• Primary DLBCL of the central nervous system requires treatment with high-dose methotrexate; addition of high-dose cytarabine can improve complete remission rate 1
• Primary DLBCL of the testis requires CNS prophylaxis and consideration of prophylactic irradiation of the contralateral testis in localized disease 1
• Primary mediastinal large B-cell lymphoma (PMBL) is a distinct entity where R-CHOP-21 is not established as the definitive treatment option 1

Treatment Implementation

• For cases with high tumor load, special precautions (e.g., corticosteroid pre-phase) should be taken to avoid tumor lysis syndrome 1, 2
• Dose reductions due to hematological toxicity should be avoided to maintain treatment efficacy 1, 2
• Febrile neutropenia justifies prophylactic use of hematopoietic growth factors in patients treated with curative intent 1, 2

Response Evaluation and Follow-up

• Radiological tests should be repeated after 3-4 cycles and after completion of treatment 1, 2
• PET is highly recommended for post-treatment assessment to define complete remission 1
• Follow-up includes history and physical examination every 3 months for 1 year, every 6 months for 2 more years, and then once a year 1, 4
• Blood count and LDH should be monitored at 3,6,12, and 24 months 1, 4
• CT scans are recommended at 6,12, and 24 months after treatment completion 1, 4
• Routine surveillance with PET scan is not recommended 1, 4

Management of Relapsed Disease

• Histological verification should be obtained whenever possible, especially for relapses occurring >12 months after initial diagnosis 1, 4
• For suitable patients (adequate performance status, age <65-70 years), salvage regimen with rituximab and chemotherapy followed by high-dose treatment with stem-cell support is recommended 1, 4
• Salvage regimens such as R-DHAP (rituximab, cisplatin, cytosine-arabinoside, dexamethasone) or R-ICE (rituximab, ifosfamide, carboplatin, etoposide) are commonly used 1

Efficacy and Prognosis

• Despite optimal treatment, approximately 30% of DLBCL cases will ultimately relapse 1, 5
• Early identification of relapse is important as salvage therapy can still be curative in some patients 4, 5
• The addition of rituximab to CHOP has significantly improved outcomes in DLBCL, with 2-year event-free survival increasing from 38% to 57% and overall survival from 57% to 70% 6