PT  - JOURNAL ARTICLE
AU  - Khan, Khuda D.
AU  - Emmanouilides, Christos
AU  - Benson, Don M.
AU  - Hurst, Deborah
AU  - Garcia, Pablo
AU  - Michelson, Glenn
AU  - Milan, Sandra
AU  - Ferketich, Amy K.
AU  - Piro, Lawrence
AU  - Leonard, John P.
AU  - Porcu, Pierluigi
AU  - Eisenbeis, Charles F.
AU  - Banks, Amy L.
AU  - Chen, Lei
AU  - Byrd, John C.
AU  - Caligiuri, Michael A.
TI  - A Phase 2 Study of Rituximab in Combination with Recombinant Interleukin-2 for Rituximab-Refractory Indolent Non-Hodgkin's Lymphoma
AID  - 10.1158/1078-0432.CCR-06-1571
DP  - 2006 Dec 01
TA  - Clinical Cancer Research
PG  - 7046--7053
VI  - 12
IP  - 23
4099  - http://clincancerres.aacrjournals.org/content/12/23/7046.short
4100  - http://clincancerres.aacrjournals.org/content/12/23/7046.full
SO  - Clin Cancer Res2006 Dec 01; 12
AB  - 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 <6 months). I.V. rituximab was given at 375 mg/m2 (weeks 1-4). S.C. rIL-2 was given thrice a week at 14 MIU (weeks 2-5) and at 10 MIU (weeks 6-9). 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.