From the Guidelines
The current frontline treatment for stage four diffuse large B-cell lymphoma (DLBCL) without double-hit features is R-CHOP21 × 6, which consists of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. This treatment strategy is recommended based on the guidelines outlined in the Annals of Oncology 1. The standard regimen typically involves 6 cycles of treatment given every 21 days.
Key Components of R-CHOP21 × 6
- Rituximab is administered at 375 mg/m² IV on day 1
- Cyclophosphamide at 750 mg/m² IV on day 1
- Doxorubicin at 50 mg/m² IV on day 1
- Vincristine at 1.4 mg/m² (capped at 2 mg) IV on day 1
- Prednisone at 100 mg orally on days 1-5
Supportive Care and Prophylaxis
Supportive care includes antiemetics, growth factor support if indicated, and prophylaxis against tumor lysis syndrome and infections as needed. CNS prophylaxis may be considered for high-risk patients, as outlined in the guidelines 1.
Treatment Response and Assessment
Treatment response is typically assessed with PET/CT scan after 2-4 cycles and at the end of treatment. The R-CHOP regimen has been the standard of care for over two decades because it significantly improves survival compared to CHOP alone 1.
Rationale for R-CHOP21 × 6
The addition of rituximab, a monoclonal antibody targeting CD20 on B-cells, enhances the cytotoxic effects of chemotherapy by directly inducing apoptosis and activating immune-mediated killing of lymphoma cells. This regimen achieves complete remission in approximately 60-70% of patients with advanced DLBCL.
Considerations for Patient Stratification
Treatment strategies should be stratified according to age, IPI, and feasibility of dose-intensified approaches, as outlined in Table 3 of the guidelines 1. Whenever available, the inclusion in a clinical trial is recommended. In cases with high tumor load, precautions such as the administration of prednisone (p.o.) several days as ‘prephase’ treatment are advised to avoid tumor lysis syndrome 1.
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 Responding patients underwent a second randomization to receive RITUXAN or no further therapy. Among all enrolled patients, 62% had centrally confirmed DLBCL histology, 73% had Stage III–IV disease, 56% had IPI scores greater than or equal to 2,86% had ECOG performance status of < 2,57% had elevated LDH levels, and 30% had two or more extranodal disease sites involved Efficacy results are presented in Table 15. These results reflect a statistical approach which allows for an evaluation of RITUXAN administered in the induction setting that excludes any potential impact of RITUXAN given after the second randomization Analysis of results after the second randomization in NHL Study 7 demonstrates that for patients randomized to R-CHOP, additional RITUXAN exposure beyond induction was not associated with further improvements in progression-free survival or overall survival Table 15 Efficacy Results in NHL Studies 7,8, and 9 Study 7(n = 632) R-CHOPCHOP Main outcomeProgression-free survival(years)
- NE = Not reliably estimable. † R-CHOP vs. CHOP. ‡ Significant at p < 0.05,2-sided. § Kaplan-Meier estimates. Median of main outcome measure3.11.6 Hazard ratio†0.69‡ Overall survival at 2 years§74%63% Hazard ratio†0.72‡
The current frontline treatment for stage four diffuse large B cell lymphoma that does not have a double hit is R-CHOP 2.
- Key components of this treatment include:
- Rituximab: an anti-CD20 antibody
- Cyclophosphamide: an alkylating agent
- Doxorubicin: an anthracycline
- Vincristine: a vinca alkaloid
- Prednisone: a corticosteroid This treatment has been shown to improve progression-free survival and overall survival in patients with DLBCL compared to CHOP alone 2.
From the Research
Current Frontline Treatment for Stage Four Diffuse Large B Cell Lymphoma
- The current standard of care for frontline treatment of diffuse large B-cell lymphoma (DLBCL) is R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) 3, 4, 5, 6.
- However, recent studies have shown promising results with novel regimens, such as pola-R-CHP (polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin, and prednisone) 3, 5, 6.
- For patients with stage four DLBCL without a double hit, the frontline treatment options are being explored in ongoing randomized trials 3.
- The choice of frontline treatment may depend on individual risk factors, disease stage, and prognostic index 4, 7, 6.
Novel Regimens and Therapies
- Polatuzumab vedotin has been introduced as a potential treatment option for relapsed or refractory DLBCL, and its effectiveness in combination with R-CHP for newly diagnosed CD20-positive DLBCL has been reported 5.
- Anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy has also been introduced as a potential treatment option for relapsed or refractory DLBCL 4, 5, 6.
- Bispecific antibodies, such as epcoritamab, mosunetuzumab, and glofitamab, are being investigated for DLBCL 5.
- Other novel agents, such as tafasitamab combined with lenalidomide, CD19 antibody drug conjugate loncastuximab tesirine, and oral selective inhibitor of nuclear export selinexor, are also being evaluated for DLBCL 5, 6.