A Phase 2 Study of Rituximab in Combination with Recombinant Interleukin-2 for Rituximab-Refractory Indolent Non-Hodgkin's Lymphoma

Autor: Amy Banks, Pablo Garcia, Pierluigi Porcu, Lawrence D. Piro, Michael A. Caligiuri, Amy K. Ferketich, John P. Leonard, Don M. Benson, Lei Chen, Khuda D. Khan, Sandra Milan, Glenn C. Michelson, Christos Emmanouilides, John C. Byrd, Deborah Hurst, Charles F. Eisenbeis
Rok vydání: 2006
Předmět:
Male
Oncology
Cancer Research
Phases of clinical research
Kaplan-Meier Estimate
Antibodies
Monoclonal
Murine-Derived
immune system diseases
Aldesleukin
hemic and lymphatic diseases
Antineoplastic Combined Chemotherapy Protocols
Medicine
Aged
80 and over
Antibody-dependent cell-mediated cytotoxicity
Lymphoma
Non-Hodgkin
Antibodies
Monoclonal
Middle Aged
Recombinant Proteins
Treatment Outcome
Injections
Intravenous
Monoclonal
Female
Rituximab
medicine.drug
Adult
medicine.medical_specialty
Drug-Related Side Effects and Adverse Reactions
Maximum Tolerated Dose
Combination therapy
Injections
Subcutaneous
chemical and pharmacologic phenomena
Disease-Free Survival
Drug Administration Schedule
Antigens
CD
Internal medicine
Humans
Aged
Neoplasm Staging
Polymorphism
Genetic
Dose-Response Relationship
Drug
business.industry
Receptors
IgG
medicine.disease
Non-Hodgkin's lymphoma
Lymphoma
Immunology
Interleukin-2
business
Follow-Up Studies
Zdroj: Clinical Cancer Research. 12:7046-7053
ISSN: 1557-3265
1078-0432
DOI: 10.1158/1078-0432.ccr-06-1571
Popis: Purpose: The incidence of non-Hodgkin's lymphoma (NHL), the fifth most common malignancy in the United States, has increased over 70% in the last 30 years. Fifty percent to 75% of patients with low-grade or follicular NHL respond to rituximab therapy. However, responses are generally of limited duration, and complete responses are rare. Preclinical work suggests that human recombinant interleukin-2 (rIL-2; aldesleukin, Proleukin) enhances rituximab efficacy. Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of action of rituximab. rIL-2 induces expansion and activation of Fc receptor (FcR)–bearing cells, thereby enhancing ADCC. Therefore, a large, multicenter phase 2 trial to assess the effects of rIL-2 on rituximab therapy in patients with rituxumab-refractory low-grade NHL was conducted. Experimental Design: The combination of rituximab and rIL-2 was studied in 57 patients with rituximab-refractory low-grade NHL (i.e., patients must have received a single-agent course of rituximab and showed no tumor response, or had a response lasting Results: Rituximab plus rIL-2 combination therapy was safe and generally well tolerated, but responses were low. Fifty-seven patients were enrolled with 54 evaluable for response; however, only five responses (one complete and four partial) were observed. Correlative data indicate that rIL-2 expanded FcR-bearing cells and enhanced ADCC. However, other factors, such as FcγR polymorphisms in patients refractory to single-agent rituxumab and heterogeneous tumor biology, may have influenced the lack of clinical efficacy seen with this combination therapy. Conclusions: rIL-2 expands FcR-bearing cellular subsets in vivo and enhances in vitro ADCC of rituxumab. However, these findings do not directly translate into meaningful clinical benefit for patients with rituxumab-refractory NHL.
Databáze: OpenAIRE
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