Abstract LB-204: Results of a Phase 3 trial evaluating safety and efficacy of specific immunotherapy, recombinant idiotype (Id) conjugated to KLH (Id-KLH) with GM-CSF, compared to non-specific immunotherapy, KLH with GM-CSF, in patients with follicular non-Hodgkin's lymph

Abstract

Abstract Introduction: MyVax® personalized immunotherapy consists of the tumor-specific Id protein, produced using molecular methods, conjugated to Keyhole limpet hemocyanin (KLH) and administered in a series of sc immunizations with GM-CSF. Methods: This is a multi-center, randomized, blinded, controlled trial examining the safety and efficacy of MyVax compared to a control immunotherapy in patients with previously untreated follicular non-Hodgkin's lymphoma (fNHL). Patients received 8 cycles of CVP followed by a 6-month rest period. Patients who maintained at least a partial response for 6 months post CVP were randomized to receive MyVax or control immunotherapy in a 2:1 ratio. All patients received GM-CSF at each immunization and for the next 3 days. Patients received a series of 7 immunizations over 24 weeks. Sera for Id- and KLH-specific humoral immune response (IR) assays were collected prior to, during, and for 1 year following immunization. Results: 287 patients were randomized and 278 patients received at least one immunization. Anti-Id IRs were observed in 41.0% of evaluable patients. No statistical difference in PFS and time to subsequent anti-lymphoma therapy (SALT) was seen in the patients who received MyVax compared to those who received the control immunotherapy. Both arms of the study have an apparent plateau of PFS >30% at 5 years. A highly statistically significant improvement in PFS (P=0.0017) was seen in patients mounting an anti-Id immune response (IR+) vs. IR- patients with >2-fold increase (39.7 vs 18.1 months) in PFS. The IR+ patients show a statistically significant improvement in PFS over the control immunotherapy patients while there is not a statistically significant difference in PFS between the IR patients and the control immunotherapy patients. The degree of clinical benefit correlates with the titer of the anti-Id IRs, but not with the titer of the anti-KLH IRs. High risk FLIPI patients did as well as the other patients in both PFS and SALT. Clinical response improvements were observed on both arms post immunization. Conclusions: There was no difference in PFS between the patients receiving specific immunotherapy versus those receiving control immunotherapy. As previously reported in Phase II trials, fNHL patients mounting anti-Id IRs have a significantly improved clinical outcome.