Background: Patient specific active idiotype immunotherapy with immunoglobulin idiotype is a promising new therapy for follicular NHL. Response to therapy may include both humoral and cellular anti-idiotypic immunity, but it is not clear which is most important. Prior studies have suggested that immunoglobulin FCgammaRIIIa (FCgRIIIa) polymorphisms at position 158 valine (V) or phenylalanine (F) effect the response to treatment with rituximab as well as outcomes from idiotype immunotherapy following objective response to chemotherapy. Here we present data assessing the correlation of FCgRIIIa polymorphisms and outcomes from idiotype immunotherapy following treatment with rituximab.
Treatment: We determined the FCgRIIIa genotype using a SSCP method with genomic DNA isolated from 55 rituximab-naïve patients treated on a Phase II trial of mitumprotimut-T (FavId®, Id-KLH) (
Results: DNA was isolated from all 55 patients and successfully analyzed by SSCP for polymorphisms at position 158 of FCgRIIIa. Nine of 55 patients were V/V (16%), 27 were F/F (49%) and 19 were heterozygous V/F (35%). Overall, the 3 month response rate CR+PR) was 31/55 (56%) and the best overall response rate was 39/55 (71%). The 3 month response (post rituximab) was 5/9 (56%) for V/V, 9/19 (47%) for V/F and 17/27 (63%) for F/F patients. Best response was 6/9 (67%) for V/V, 12/19 (63%) for V/F and 21/27 (78%) for F/F patients. Median TTP was 19.5 months for V/V, 22.3 months for V/F and 18 months for F/F patients. The PFS at 1 year post initiation of rituximab was 57% for V/V, 61% for VF and 68% for FF patients while at the median follow-up of 3.5 years the PFS was 31% for V/V, 42% for V/F and 31% for F/F patients.
Conclusions: FCgRIIIa polymorphisms were not associated with response rate or time to progression following a treatment program consisting of single agent rituximab followed by idiotype vaccination with mitumprotimut-T in rituximab-naïve patients. Results from an ongoing randomized Phase III study will assess the efficacy of this combined therapy, but these data suggest that long term PFS in patients receiving an idiotype vaccine following rituximab may rely more on a cell mediated immune response rather than a humoral response to idiotype.
Disclosure:Employment: Daniel P. Gold, Ph.D. is an employee of Favrille, Inc. Ownership Interests:; Daniel P. Gold, Ph.D. is employed by Favrille, Inc., and owns shares and options of Favrille stock. Honoraria Information: Dr. Maloney has received an honoraria of less than $5,000.00 for his participation on Favrille’s advisor’s committees. Membership Information: Dr. Maloney has participated as a member of Favrille’s advisory committees.