Maintenance Rituximab After Cyclophosphamide, Vincristine, and Prednisone Prolongs Progression-Free Survival in Advanced Indolent Lymphoma: Results of the Randomized Phase III ECOG1496 Study

New York University Medical Center, New York, NY 10016, USA.
Journal of Clinical Oncology (Impact Factor: 18.43). 05/2009; 27(10):1607-14. DOI: 10.1200/JCO.2008.17.1561
Source: PubMed


To determine if maintenance rituximab (MR) after standard chemotherapy improves progression-free survival (PFS) in advanced-stage indolent lymphoma.
Patients with stage III-IV indolent lymphoma with responding or stable disease after cyclophosphamide, vincristine, and prednisone (CVP) chemotherapy were stratified by initial tumor burden, residual disease after CVP (minimal or gross), and histology, and randomly assigned to observation (OBS) or MR 375 mg/m(2) once per week for 4 weeks every 6 months for 2 years. PFS was the primary end point.
Three hundred eleven (282 with follicular lymphoma) evaluable patients who received CVP were randomly assigned to OBS (n = 158) or MR (n = 153). Best response improved in 22% MR versus 7% OBS patients (P = .00006). Toxicity was minimal in both study arms. Three-year PFS after random assignment was 68% MR versus 33% OBS (hazard ratio [HR] = 0.4; P = 4.4 x 10(-10) [all patients]) and 64% MR v 33% OBS (HR = 0.4; P = 9.2 x 10(-8) [patients with follicular lymphoma]). There was an advantage for MR regardless of Follicular Lymphoma International Prognostic Index score, tumor burden, residual disease, or histology. In multivariate analysis of MR patients, minimal disease after CVP was a favorable prognostic factor. OS at 3 years was 92% MR versus 86% OBS (HR = 0.6; log-rank one-sided P = .05) and, among patients with follicular lymphoma, OS was 91% MR versus 86% (HR = 0.6; log-rank one-sided P = .08). A trend favoring MR was observed among patients with high tumor burden (log-rank one-sided P = .03).
The E1496 study provides the first phase III data in untreated indolent lymphoma that MR after chemotherapy significantly prolongs PFS.

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Available from: Stanley R Frankel, May 21, 2014
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    • "Progressive disease was deWned as a more than 25% increase in the sum of the products of pretreatment lesions or new disease. Stable disease met none of these criteria (Hochster et al. 2009). "
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    ABSTRACT: In international prognostic index (IPI) risk-tailored adult patients with diffuse large B-cell lymphoma (DLBCL), it is still unclear whether the addition of maintenance rituximab (MR) improves progression-free (PFS) and overall survival (OS), after RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy. In our study, 207 patients (age: 21-59 years) received six 14-day cycles of RCHOP and gained overall response. After RCHOP, 98 patients were enrolled in the observation (OBS) arm. 109 patients continued to receive MR therapy. In IPI risk <2 profile, PFS at 5 years reached 72.9% (MR arm) versus 56% (OBS arm) (P = 0.033). In IPI risk ≥2 profile, PFS estimation at 5 years was 44.9% (MR arm) versus 33.5% (OBS arm) (P = 0.006). It is noteworthy that patients with IPI ≥2 who received MR achieved PFS similar to that for patients in the OBS arm with the IPI <2, 44.9% versus 56% (P = 0.97). In patients with an IPI <2, OS at 5 years was 83.2% (MR arm) versus 81.2% (OBS arm) (P = 0.708). In patients with an IPI ≥2, 5-year OS estimation was 44.6% (MR arm) versus 40.5% (OBS arm) (P = 0.067). Subgroup analysis of patients with an IPI ≥3 risk profile shows a survival benefit for patients receiving MR. OS at 5 years was 62% (MR arm) versus 49% (OBS arm), (P = 0.033). In conclusion, maintenance rituximab after RCHOP improves progression-free survival. In addition, overall survival is improved for patients with an IPI ≥3 risk profile receiving MR.
    Journal of Cancer Research and Clinical Oncology 11/2011; 138(1):125-32. DOI:10.1007/s00432-011-1074-1 · 3.08 Impact Factor
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    • "In addition, the use of maintenance rituximab following chemotherapy has been shown to be superior to observation in terms of response duration among NHL patients not previously treated with rituximab [Maloney, 2008; Forstpointner et al. 2006]. Furthermore, a recent multicenter study of maintenance rituximab in FL patients showed a significant improvement in PFS after 2 years when compared with patients on observation only [Salles et al. 2011; Hochster et al. 2009]. However, the use of rituximab maintenance (R-M) after front-line chemotherapy may be associated with additional side effects compared with observation (OBS). "
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    ABSTRACT: The impact on health related quality of life (HRQoL) of rituximab maintenance (R-M) versus observation (OBS) after induction for treatment of follicular lymphoma (FL) is unclear. We reviewed the charts of 137 patients (53% female, 87% White, age 61.0 ± 12.4 years) who received either R-M (n = 53) or OBS (n = 84) after chemotherapy induction for newly diagnosed FL at community oncology practices within the US. Patients (65% with advanced disease; 48% with a high FLIPI score [3-5]) had completed ≥1 Patient Care Monitor HRQoL survey in the period following front-line therapy, and were excluded if they had progressed during front-line therapy. Linear mixed models showed that postinduction, most symptoms were stable, with patients on R-M reporting HRQoL that was equal to that reported by OBS patients. Among R-M patients, receipt of rituximab was associated with improved psychological symptoms.
    06/2011; 2(3):129-39. DOI:10.1177/2040620711407675
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    • "In addition to the impressing results of Rituximab as part of first line and relapse treatment, Rituximab maintenance therapy is effective in relapsed FL [20-22]. Rituximab maintenance therapy has also been shown to prolong PFS after first line therapy in two prospective randomized trials [23,24]. "
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    ABSTRACT: The optimal treatment of early stage follicular Lymphoma is a matter of debate. Radiation therapy has frequently been applied with a curative approach beside watchful waiting. Involved field, extended field and total nodal radiation techniques are used in various protocols, but the optimal radiation field still has to be defined. Follicular lymphoma is characterized by stable expression of the CD20 antigen on the tumour cells surface. The anti CD20 antibody Rituximab (Mabthera®) has shown to be effective in systemic therapy of FL in primary treatment, relapse and maintenance therapy. The MIR (Mabthera® and Involved field Radiation) study is a prospective multicenter trial combining systemic treatment with the anti CD20 antibody Rituximab (Mabthera®) in combination with involved field radiotherapy (30 - 40 Gy). This trial aims at testing the combination's efficacy and safety with an accrual of 85 patients.Primary endpoint of the study is progression free survival. Secondary endpoints are response rate to Rituximab, complete remission rate at week 18, relapse rate, relapse pattern, relapse free survival, overall survival, toxicity and quality of life. The trial evaluates the efficacy of Rituximab to prevent out-filed recurrences in early stage nodal follicular lymphoma and the safety of the combination of Rituximab and involved field radiotherapy. It also might show additional risk factors for a later recurrence (e.g. remission state after Rituximab only). ClinicalTrials (NCT): NCT00509184.
    BMC Cancer 02/2011; 11(1):87. DOI:10.1186/1471-2407-11-87 · 3.36 Impact Factor
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