The Clinical and Economic Value of Rituximab for the Treatment of Hematologic Malignancies

Charles M. Farber, MD, PhD; and Randy C. Axelrod, MD | March 15, 2011


Rituximab is a humanized monoclonal antibody that is used for the treatment of a wide variety of B-cell–derived hematologic malignancies, including follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), the 2 most commonly occurring subtypes of non-Hodgkin lymphoma, as well as chronic lymphocytic leukemia (CLL). Multiple studies show that rituximab improves clinical outcomes and is a cost-effective therapy for FL, DLBCL, and CLL. Recent results from the PRIMA study have demonstrated that rituximab as maintenance therapy prolongs the duration of response and significantly reduces the risk of progression. Rituximab continues to undergo active clinical investigation to optimize survival outcomes and safety in both initial treatment and maintenance settings, as well as in combination with other targeted therapies. We review the clinical evidence demonstrating the efficacy, safety, and cost of rituximab in the treatment of B-cell–derived diseases and discuss ongoing avenues of investigation of the drug.
Since US Food and Drug Administration (FDA) approval in 1997, rituximab (Rituxan) has been one of the most widely prescribed biological agents in the United States.1 The ubiquitous expression of the target protein CD20 on the surface of B lymphocytes and the fact that the vast majority of non-Hodgkin lymphomas (NHLs) are B-cell malignancies have provided the rationale for the development of this humanized monoclonal antibody, which has become one of the most commonly used therapeutic agents for this group of malignancies (Table 1).2-5

In combination with chemotherapy, rituximab significantly improves survival outcomes for patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL), the 2 most commonly diagnosed subtypes of NHL.6-11 Rituximab as maintenance therapy has been shown to significantly reduce the risk for progression in patients with newly diagnosed and relapsed FL.12,13 Further, chemoimmunotherapy-containing rituximab significantly improves complete response (CR), progression-free survival (PFS), and overall survival (OS) rates for patients with either previously untreated, relapsed, or refractory chronic lymphocytic leukemia (CLL).14,15 Based on such efficacy data, rituximab is FDA-approved for the treatment of FL, DLBCL, and CLL in a number of settings.16 Importantly, studies show rituximab to be a cost-effective treatment with a very favorable toxicity profile and reduced needs for ancillary medical care.17-21 We review the clinical evidence supporting the benefits and safety of treatment with rituximab, the costeffectiveness of the therapy, and continued clinical investigation to optimize outcomes and increase convenience of use.


Aggressive/Diffuse Large B-Cell Lymphoma

Untreated Disease. Rituximab, combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (R-CHOP), is the only approved biologic agent reported to significantly improve survival rates for a broad range of patients with untreated DLBCL, including both the young and the elderly, as demonstrated in 3 large-scale clinical trials (Table 2).10,11,22 Both the LNH 98-5 and E4494 trials were conducted in untreated patients who were 60 years and older.11,22

Long-term follow-up after 10 years in the LNH 98-5 study showed treatment with R-CHOP continued to result in a significant survival benefit (43.5% vs 27.6%; P <.0001).11 The median PFS from this latest analysis was 8.4 years for R-CHOP compared with 3.5 years for CHOP alone. Significant improvements in the 10-year PFS (36.5% vs 20.1%, P <.0001), event-free survival (EFS) (34% vs 19%, P <.001), and disease-free survival (64.5% vs 42.6%, P <.001) rates also were observed. In the E4494 trial similar improved clinical benefits were observed with R-CHOP (3-year time to treatment failure and OS measures) compared with CHOP alone (Table 2).22 Both trials demonstrated that improved clinical benefits were maintained across all analyzed subgroups. Six-year follow-up results from the phase III MInT trial conducted in 834 younger (≤60 years) patients who had a favorable prognosis and were treated with rituximab in combination with CHOP or CHOP-like chemotherapy showed significantly improved 6-year EFS and OS rates compared with CHOP or CHOPlike chemotherapy alone (74% vs 56%, P <.001; 90% vs 80%, P = .001, respectively).10

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