Rituximab in combination with fludarabine chemotherapy in low-grade or follicular lymphoma.
ABSTRACT To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naive or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma.
This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks.
An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naive and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal.
Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.
Article: Monoclonal Antibodies in Lymphomas[Show abstract] [Hide abstract]
ABSTRACT: Immunotherapy has markedly altered the treatment options available for patients with non-Hodgkin’s lymphoma (NHL). Monoclonal antibodies have revolutionized the treatment of cancers in two respects. First, they represent a therapy with a different mechanism of action than chemotherapy. By providing an alternative type of attack, they may improve outcomes through better efficacy. Second, they represent a major step forward in improving the tolerability of cancer therapies. As a more targeted therapy, monoclonal antibodies enable patients to receive treatment that might not have otherwise been tolerated, potentially extending their lives and decreasing symptomatology. Although each monoclonal antibody was initially developed for one indication, their approvals have enabled exploration of other possible indications. We are only beginning to understand the breadth of diseases, malignant and non-malignant, that might benefit from treatment with these monoclonal antibodies, and how best to use them. Attempts to further improve outcomes in NHL are being explored, including the role of modifications of dose and schedule, chemotherapy combinations, and through the use of other biologics. Monoclonal antibodies represent the epitome of targeted therapy and have the potential to move forward the treatment of lymphomabreak more than any other development since the first use of multiagent chemotherapy.
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ABSTRACT: Monoclonal antibodies are a new class of agents that target tumor-associated antigens. Advances in hybridoma technologies in the early 1980s allowed the creation of monoclonal antibodies with high specificity in addition to the development of monoclonal antibodies that can be linked to anticancer drugs, radioisotopes, or toxins. Several cancer-specific monoclonal antibodies have received approval by the United States Food and Drug Administration (FDA) and many more are currently under clinical investigation. This review summarizes the monoclonal antibodies either approved by the FDA or in development for the treatment of hematologic malignancies. Rituximab, which targets the CD20 antigen, has revolutionized the treatment of B-cell lymphoma. The standard of care for front-line treatment of follicular center cell lymphoma and diffuse large B-cell lymphomas, which are the predominate two lymphomas in the Western world, is rituximab combined with chemotherapy. Second-generation anti-CD20 monoclonal antibodies are currently being studied in phase II and III trials. Radioimmunotherapy with anti-CD20 antibodies has also been approved by the FDA for the second-line treatment of follicular lymphoma. Additional antibodies and immunoconjugates targeting a variety of B-cell-associated antigens are also in the clinic for hematologic malignancies including antibodies targeting CD22, CD23, CD80, CD40, CD30, CD4, CD37, CD74, CTLA-4, VEGF, and the insulin-like growth factor 1 receptor. We believe that many of these monoclonal antibodies and immunoconjugates will become standard of care for a variety of hematologic malignancies.
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ABSTRACT: To evaluate the efficacy of rituximab maintenance in 60- to 75-year-old patients with advanced follicular lymphoma responding to brief first-line chemoimmunotherapy followed by rituximab consolidation. A total of 234 treatment-naive 60- to 75-year-old patients began chemoimmunotherapy with four monthly courses of rituximab, fludarabine, mitoxantrone, and dexamethasone (R-FND) followed by four weekly cycles of rituximab consolidation. Of these, 210 patients completed the planned treatment, and 202 responders were randomly assigned to rituximab maintenance (arm A) for 8 months, once every 2 months for a total of four doses, or to observation (arm B). Median ages in arms A and B were 66 and 65 years, respectively. After induction and consolidation therapy, the overall response rate was 86%, with 69% complete remissions (CR). After a 42-month median follow-up from diagnosis, 3-year progression-free survival (PFS; the primary end point) and overall survival (OS) were 66% (95% CI, 59% to 72%) and 89% (95% CI, 85% to 93%), respectively. After randomization, 2-year PFS was 81% for rituximab maintenance versus 69% for observation, with a hazard ratio of 0.74 (95% CI, 0.45 to 1.21; P = .226), although this was not statistically significant. No differences between the two arms were detected for OS. Overall, the regimen was well-tolerated. The most frequent grade 3 to 4 toxicity was neutropenia (25% of treatment courses), with 13 infections. Two toxic deaths (0.8%) occurred during induction treatment. A brief R-FND induction plus rituximab consolidation achieved excellent results with high CR and PFS rates, supporting the feasibility of this regimen in patients older than 60 years. A short rituximab maintenance did not achieve a statistically significant PFS improvement over observation.Journal of Clinical Oncology 08/2013; 31(27). DOI:10.1200/JCO.2012.44.8290 · 17.88 Impact Factor