What is the recommended first-line treatment for Diffuse Large B-Cell Lymphoma (DLBCL)?

First-Line Treatment for Diffuse Large B-Cell Lymphoma (DLBCL)

R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) is the standard first-line treatment for DLBCL, with the specific regimen tailored based on patient age, International Prognostic Index (IPI), and feasibility of dose-intensified approaches. 1

Treatment Approach Based on Patient Characteristics

Young Low-Intermediate Risk Patients (aaIPI = 0-1)

• Six cycles of R-CHOP given every 21 days (R-CHOP-21) with radiotherapy to sites of previous bulky disease is effective based on the MINT study 1
• Alternatively, R-ACVBP (rituximab, doxorubicin, vindesine, cyclophosphamide, bleomycin, and prednisolone) given every 2 weeks followed by sequential consolidation has shown improved survival compared to R-CHOP in this category, though radiotherapy was omitted in both arms of this trial 1
• Either R-CHOP-21 × 6 with radiotherapy to bulky disease sites or the intensified R-ACVBP regimen is recommended for this patient group 1

Young High and High-Intermediate Risk Patients (aaIPI ≥ 2)

• No definitive standard exists for this subgroup; clinical trial enrollment should be prioritized 1
• Six to eight cycles of R-CHOP combined with eight doses of rituximab given every 21 days is most frequently applied 1
• Dose-dense treatment with R-CHOP given every 14 days (R-CHOP-14) has not demonstrated survival advantage over standard R-CHOP-21 1, 2
• Intensive regimens like R-ACVBP or R-CHOEP (rituximab, cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisolone) are frequently used but have not been directly compared with R-CHOP in this category 1

Patients Aged 60-80 Years

• Six to eight cycles of R-CHOP plus eight doses of rituximab given every 21 days is the current standard 1
• If R-CHOP is given every 14 days, six cycles of CHOP with eight cycles of rituximab are sufficient 1
• R-CHOP-14 did not demonstrate survival advantage over R-CHOP-21 in this age group 1
• A comprehensive geriatric assessment is recommended to guide treatment choices 1

Patients Aged >80 Years

• R-CHOP can usually be used up to 80 years of age in fit patients 1
• For patients over 80, R-miniCHOP (attenuated doses) can induce complete remission and long survival in healthy patients 1
• Doxorubicin substitution with etoposide or liposomal doxorubicin, or even its omission, can be considered in patients with cardiac dysfunction or otherwise unfit 1

Important Treatment Considerations

Prephase Treatment

• In cases with high tumor load, administering prednisone (100 mg p.o.) for several days as "prephase" treatment is advised to avoid tumor lysis syndrome 1

Dose Intensity

• Dose reductions due to hematological toxicity should be avoided to maintain treatment efficacy 1
• Febrile neutropenia justifies prophylactic use of hematopoietic growth factors in patients treated with curative intent and in all elderly patients 1

CNS Prophylaxis

• Patients with high-intermediate and high-risk IPI, especially those with more than one extranodal site or elevated LDH, are at higher risk of CNS relapse 1
• CNS prophylaxis should be recommended in this population 1
• Intravenous high-dose methotrexate may be more effective than intrathecal injections 1
• Testicular lymphoma must receive CNS prophylaxis 1

Special Considerations for Specific DLBCL Subtypes

Primary DLBCL of the Central Nervous System

• Treatment must contain high-dose methotrexate 1
• Addition of high-dose cytarabine can improve complete remission rate and outcome 1
• CNS irradiation is usually administered as consolidation 1

Primary DLBCL of the Testis

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

Treatment Efficacy and Monitoring

• Response evaluation should be performed after 3-4 cycles and after completion of treatment 1
• PET scanning, when positive at baseline, is part of the updated response criteria 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
• Minimal adequate radiological examinations at 6,12, and 24 months after treatment by CT scan are indicated 1
• Routine surveillance with PET scan is not recommended 1

Relapsed/Refractory Disease

• Histological verification should be obtained whenever possible, especially for relapses >12 months after initial diagnosis 1
• 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
• Common salvage regimens include R-DHAP (rituximab, cisplatin, cytosine arabinoside, and dexamethasone) or R-ICE (rituximab, ifosfamide, carboplatin, and etoposide) 1