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Systemic Interleukin-2 and Adoptive Transfer of Lymphokine-Activated Killer Cells Improves Antibody-Dependent Cellular Cytotoxicity in Patients with Relapsed B-Cell Lymphoma Treated with Rituximab

Authors' Affiliations: ¹ Division of Hematology and Oncology, Loma Linda University Medical Center, Loma Linda, California; ² Division of Hematologic Malignancies, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland; ³ Division of Hematology-Oncology, Ohio State University, Columbus, Ohio; ⁴ Department of Clinical Transplant Research, Fred Hutchinson Cancer Research Center, Seattle, Washington; and ⁵ Sarah Cannon Research Institute, Nashville, Tennessee

Requests for reprints: Jesús G. Berdeja, Division of Hematology and Oncology, Department of Medicine, Loma Linda University Medical Center, 11234 Anderson Street, Room 1531, Loma Linda, CA 92354. Phone: 909-558-4910; Fax: 909-558-0219; E-mail: jberdeja{at}ahs.llumc.edu.

Purpose: Murine models have shown that antibody-dependent cellular cytotoxicity (ADCC) can be improved with addition of lymphokine-activated killer (LAK) cells to monoclonal antibodies. A pilot trial of rituximab and LAK cells in patients with rituximab-refractory CD20⁺ lymphoma was conducted to evaluate this approach.

Experimental Design: Ten patients received 3 million units/m² of interleukin-2 (IL-2) i.v. qd on days 1 to 5 and leukapheresed on days 8, 9, and 10. The leukapheresis product was cultured with IL-2 for 48 h to produce LAK cells. Patients then received 375 mg/m² i.v. rituximab and LAK cells on days 10, 11, and 12. The patients also received 3 million units/m² of IL-2 i.v. for 5 days starting day 10. For safety purposes, the first three patients did not receive any LAK cell infusions.

Results: The LAK cell infusions improved the ADCC activity of peripheral blood lymphocytes compared with pretreatment activity and prevented the decline in ADCC seen after infusion of rituximab alone. Therapy was well tolerated and the most clinically significant toxicities were fever and fatigue. Two patients achieved a partial remission and five had stable disease.

Conclusions: The results from these studies suggest that the addition of LAK cells to rituximab augments ADCC in patients with rituximab-refractory lymphoma.

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