Originally published as JCO Early Release 10.1200/JCO.2005.04.4289 on June 5 2006

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Phase II Trial of Idiotype Vaccination in Previously Treated Patients With Indolent Non-Hodgkin’s Lymphoma Resulting in Durable Clinical Responses

Charles H. Redfern, Troy H. Guthrie, Alberto Bessudo, John J. Densmore, Peter R. Holman, Nalini Janakiraman, John P. Leonard, Richard L. Levy, Richard G. Just, Mitchell R. Smith, Fred P. Rosenfelt, Peter H. Wiernik, William D. Carter, Daniel P. Gold, Teresa J. Melink, John C. Gutheil, John F. Bender

From Sharp Healthcare; University of California; Favrille Inc, San Diego; Medical Group of North County, Vista; Scripps Cancer Center, La Jolla; Tower Hematology/Oncology Medical Group, Los Angeles, CA; University of Florida, Jacksonville, FL; University of Virginia, Charlottesville, VA; Henry Ford Hospital, Detroit, MI; New York Hospital-Cornell Medical Center, New York; Our Lady of Mercy Medical Center, Bronx, NY; Oncology/Hematology Care Inc, Cincinnati, OH; and Fox Chase Cancer Center, Philadelphia, PA

Address reprint requests to John F. Bender, PharmD, Favrille Inc, 10421 Pacific Center Ct, San Diego, CA 92121; e-mail: john.bender{at}favrille.com

PURPOSE: To evaluate idiotype (Id) vaccination as a single agent in previously treated patients with indolent non-Hodgkin’s lymphoma.

PATIENTS AND METHODS: Patients underwent biopsy for determination of their lymphoma-specific Id sequence. Recombinant Id protein was manufactured and covalently linked with keyhole limpet hemocyanin (KLH) to generate Id/KLH. Patients received Id/KLH 1 mg on day 1 subcutaneously, with granulocyte-macrophage colony-stimulating factor 250 µg on days 1 to 4, monthly for 6 months. Booster injections were administered until progression. Both clinical and immune responses were evaluated.

RESULTS: Thirty-two previously treated patients received at least one injection of Id/KLH, and 31 were assessed for efficacy. Responses were observed in four patients (one complete response and three partial responses). Median time to onset of response was 5.9 months (range, 2.3 to 14.1 months). Median duration of response has not been reached but should be at least 19.4 months (range, 10.4 to 27.2+ months). Median time to progression is 13.5 months. The most common adverse events were mild to moderate injection site reactions. Six (67%) of nine patients tested demonstrated a cellular immune response, and four (20%) of 20 patients demonstrated an antibody response against their Id.

CONCLUSION: This trial demonstrates that Id/KLH alone can induce tumor regression and durable objective responses. Further study of Id/KLH is recommended in other settings where efficacy may be further enhanced as in first-line therapy or after cytoreductive therapy.

Presented in part at the 44th Annual Meeting of the American Society of Hematology, Philadelphia, PA, December 6-10, 2002; the 45th Annual Meeting of the American Society of Hematology, San Diego, CA, December 6-9, 2003; and the Pan-Pacific Lymphoma Conference, Kauai, HI, July 11-15, 2005.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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