What is the role of rituximab in the treatment of early-stage DLBCL?

Updated: Jun 12, 2019
  • Author: Shipra Gandhi, MBBS; Chief Editor: Emmanuel C Besa, MD  more...
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The use of monoclonal antibodies, particularly rituximab, has changed the treatment paradigm of patients with B-cell non-Hodgkin lymphoma, including DLBCL. Rituximab is a chimeric monoclonal antibody that targets the CD20 antigen present in normal and most of the malignant B-cells. The mechanisms by which rituximab elucidates its antitumor activity has been characterized and includes antibody-dependent cellular cytotoxicity (ADCC), complement-mediated cytotoxicity (CMC), and activation of intracellular pathways leading to apoptosis. Preclinical models have demonstrated that rituximab potentiates the effect of several chemotherapeutic agents. [86] In contrast to what has been observed in low-grade lymphomas, rituximab monotherapy has limited activity in DLBCL. [87] The addition of rituximab to standard doses of chemotherapy in DLBCL has resulted in improved clinical outcomes without adding significant toxicity.

Only a few studies addressing the role of rituximab in the management of early-stage DLBCL have been conducted. The Mabthera International Trial (MInT) was studied the role of adding rituximab to standard therapy in young patients with stage I bulky or stage II-IV DLBCL. [88] The MInT enrolled 824 young patients (ie, < 60 y) with aggressive lymphoma and good IPI score (< 1 IPI risk factor). Patients were randomized to receive 6 cycles of CHOP-like chemotherapy with or without rituximab. After a median follow-up period of 3 years, the event-free survival (EFS) and OS were improved significantly by the addition of rituximab to systemic chemotherapy. Of interest, in a subset analysis of the patients with early stage or bulky disease, the addition of IF-XRT as consolidation following chemoimmunotherapy did not improve clinical endpoints. [88]

The addition of rituximab to combined-modality treatment in DLBCL was evaluated in a Southwest Oncology Group (SWOG) study and reported by Persky et al. [89] The SWOG conducted a phase II clinical trial evaluating the addition of rituximab to an abbreviated course of CHOP chemotherapy followed by IF-XRT. The study enrolled 60 patients with limited-stage DLBCL. PFS and OS were 88% and 92%, respectively, and were considered superior to historical (chemotherapy–IF-XRT) controls, for which PFS was 78% and OS was 88%. [89] The current literature supports the addition of rituximab in the management of early-stage DLBCL to standard doses of CHOP chemotherapy.

The length of therapy and the use of radiation continue to be a subject of debate. Some clinicians strongly recommend the use of a short course (usually 3 cycles) of systemic chemoimmunotherapy followed by IF-XRT, while other physicians consider 6 cycles of rituximab in combination with CHOP equivalent and thus avoid the delayed toxicity from IF-XRT. On the other hand, it is important to stress that the multidisciplinary approach of early-stage DLBCL should be tailored according to site of disease involvement (eg, mediastinum, stomach), disease response using functional imaging, and patient comorbid conditions in an attempt to optimize the achievement of a CR that can translate into improved OS.

As the addition of rituximab to CHOP chemotherapy increases the CR, PFS, and OS of DLBCL patients, clinicians are questioning again the role of IF-XRT in the post-rituximab era. Tomita et al demonstrated that a standard strategy of 3 cycles of rituximab/CHOP (R-CHOP) followed by IF-XRT for limited-stage DLBCL could be effectively replaced by 6 cycles of R-CHOP alone. A total of 190 previously untreated patients with limited-stage DLBCL were treated with R-CHOP alone and were studied retrospectively. IF-XRT was only administered to patients achieving a CR to R-CHOP (N=5). The 5-year PFS and OS were 84% and 90, respectively. [90]


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