JCO Early Release 10.1200/JCO.2008.19.8903 on May 4 2009
Placebo-Controlled Phase III Trial of Patient-Specific Immunotherapy With Mitumprotimut-T and Granulocyte-Macrophage Colony-Stimulating Factor After Rituximab in Patients With Follicular Lymphoma
Arnold Freedman, Sattva S. Neelapu, Craig Nichols, Michael J. Robertson, Benjamin Djulbegovic, Jane N. Winter, John F. Bender, Daniel P. Gold, Richard G. Ghalie, Morgan E. Stewart, Vanessa Esquibel, Paul Hamlin
From the Dana Farber Cancer Institute, Boston, MA; The University of Texas M. D. Anderson Cancer Center, Houston, TX; Providence Cancer Center, Earle A. Chiles Research Institute, Portland, OR; Indiana University Medical Center, Indianapolis, IN; H. Lee Moffitt Cancer Center, Tampa, FL; Feinberg School of Medicine, Northwestern University, Chicago, IL; Favrille, Inc, San Diego, CA; and Memorial Sloan-Kettering Cancer Center, New York, NY.
Corresponding author: Arnold Freedman, MD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; e-mail: email@example.com .
Purpose To evaluate patient-specific immunotherapy with mitumprotimut-T (idiotype keyhole limpet hemocyanin [Id-KLH]) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in CD20+ follicular lymphoma.
Patients and Methods Patients with treatment-naive or relapsed/refractory disease achieving a complete response (CR), partial response (PR), or stable disease (SD) with four weekly rituximab infusions were randomly assigned to mitumprotimut-T/GM-CSF or placebo/GM-CSF, with doses given monthly for six doses, every 2 months for six doses, and then every 3 months until disease progression (PD). Randomization was stratified by prior therapy (treatment-naive or relapsed/refractory) and response to rituximab (CR/PR or SD). The primary end point was time to progression (TTP) from randomization.
Results A total of 349 patients were randomly assigned; median age was 54 years, 79% were treatment naive, and 86% had stage III/IV disease. Median TTP was 9.0 months for mitumprotimut-T/GM-CSF and 12.6 months for placebo/GM-CSF (hazard ratio [HR] = 1.384; P = .019). TTP was comparable between the two arms in treatment-naive patients (HR = 1.196; P = .258) and shorter with mitumprotimut-T/GM-CSF in relapsed/refractory disease (HR = 2.265; P = .004). After adjusting for Follicular Lymphoma International Prognostic Index (FLIPI) scores, the difference in TTP between the two arms was no longer significant. Overall objective response rate, rate of response improvement, and duration of response were comparable between the two arms. Toxicity was similar in the two arms; 76% of adverse events were mild or moderate, and 94% of patients had injection site reactions.
Conclusion TTP was shorter with mitumprotimut-T/GM-CSF compared with placebo/GM-CSF. This difference was possibly due to the imbalance in FLIPI scores.
Supported and sponsored by Favrille, Inc.
Presented in part at the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.