What is the treatment for localized Diffuse Large B-Cell Lymphoma (DLBCL) with double hit, stage II?

From the Guidelines

The recommended treatment for localized double-hit diffuse large B-cell lymphoma (DLBCL) at stage 2 is typically an intensive chemoimmunotherapy regimen such as dose-adjusted R-EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) for 6 cycles. This approach is based on the aggressive nature of double-hit lymphomas, which have rearrangements in both MYC and BCL2 or BCL6 genes, as noted in various studies 1, 2, 3, 4. Key considerations in the management of localized double-hit DLBCL include:

• The use of intensive chemoimmunotherapy regimens to address the aggressive nature of the disease
• The potential need for central nervous system (CNS) prophylaxis due to the higher risk of CNS involvement in double-hit lymphomas
• The role of consolidative radiation therapy to involved sites, especially for bulky disease
• The importance of close monitoring after treatment completion, with regular follow-up visits to assess response and detect potential relapse early.

Given the aggressive nature of double-hit DLBCL and its higher risk of treatment resistance and relapse compared to standard DLBCL, a more intensive approach is generally recommended even for localized disease 1. The most recent and highest quality study, although not directly addressing double-hit DLBCL, provides guidelines for the treatment of DLBCL that can be applied to this specific subtype, emphasizing the importance of chemoimmunotherapy and consideration of CNS prophylaxis and consolidative radiation therapy 1.

In terms of specific treatment strategies, dose-adjusted R-EPOCH is preferred over standard R-CHOP due to its intensity and potential to improve outcomes in aggressive lymphomas 1, 2. CNS prophylaxis with intrathecal methotrexate or high-dose systemic methotrexate is often included in the treatment plan for double-hit DLBCL due to the higher risk of CNS involvement 1, 3. After completion of chemotherapy, consolidative radiation therapy to involved sites may be considered, especially for bulky disease, to reduce the risk of local relapse 1, 4. PET/CT scans are typically performed mid-treatment and at the end of therapy to assess response and guide further management 1, 2.

Overall, the management of localized double-hit DLBCL requires a comprehensive approach that includes intensive chemoimmunotherapy, consideration of CNS prophylaxis and consolidative radiation therapy, and close monitoring after treatment completion to optimize outcomes and minimize the risk of relapse.

From the FDA Drug Label

The main outcome measure of the study was progression-free survival, defined as the time from randomization to the first of progression, relapse, or death Patients received 6 or 8 cycles of CHOP, each cycle lasting 21 days All patients in the R-CHOP arm received 4 doses of RITUXAN 375 mg/m2 on Days –7 and –3 (prior to Cycle 1) and 48–72 hours prior to Cycles 3 and 5.

The treatment for localized Diffuse Large B-Cell Lymphoma (DLBCL) with double hit, stage II is R-CHOP, which consists of:

• Rituximab 375 mg/m2 on specific days
• CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone) for 6 or 8 cycles, each cycle lasting 21 days [5] [6]

Key points:

• R-CHOP is the treatment regimen
• Rituximab is administered at a dose of 375 mg/m2 on specific days
• CHOP chemotherapy is administered for 6 or 8 cycles, each cycle lasting 21 days

From the Research

Treatment for Localized Diffuse Large B-Cell Lymphoma (DLBCL) with Double Hit, Stage II

• The standard treatment for DLBCL is R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) 7.
• For patients with limited-stage DLBCL (stage I-II), four to six cycles of R-CHOP alone or combined-modality therapy with three or four cycles and involved-site radiotherapy (RT) is recommended 8.
• Consolidative radiation therapy (RT) has been shown to improve overall survival (OS) and progression-free survival (PFS) in patients with DLBCL treated with R-CHOP chemotherapy, particularly in those with stage I or II disease 9.
• Double-hit lymphoma, which is characterized by the presence of MYC and BCL2 expression, is associated with a poorer prognosis and may require more aggressive treatment strategies 10.
• The optimal approach for extranodal limited-stage DLBCL varies according to the site of origin, and a risk-benefit assessment should be individualized and considered in a multidisciplinary fashion 8.

Considerations for Double Hit DLBCL

• Double-hit lymphoma is a high-risk subtype of DLBCL, and patients with this subtype may not benefit from standard R-CHOP therapy alone 10.
• High-dose chemotherapy and autologous stem cell transplantation (HDC-ASCT) may be considered for patients with double-hit DLBCL, particularly those who do not respond to initial therapy 10.
• Maintenance therapy with rituximab may be a useful approach to extending response duration in patients with DLBCL, but its role in double-hit DLBCL is unclear 11.