Extended Follow-Up and Analysis with Central Radiological Review of Patients Receiving FavId^® (Id/KLH) Vaccine Following Rituximab.

Background: Idiotype vaccination (Id/KLH) is a promising approach to the treatment of patients (pts) with B-cell malignancies. Our experience suggests that Id/KLH may function best in pts with lower tumor burden who are less heavily pretreated. We have conducted a phase II trial of Id/KLH following cytoreduction with rituximab in patients with treatment naive (TN) or relapsed/refractory (R/R) follicular NHL (FL).

Treatment: Pts received rituximab, 375mg/m², IV, weekly x 4, wk 1–4. Pts with without progression received Id/KLH, 1 mg, SQ, monthly x 6, starting on wk 12, with GM-CSF, 250 mcg, SQ, on days 1–4. Pts could receive booster Id/KLH on a reduced schedule until disease progression.

Results: One hundred three pts were enrolled and received rituximab; 89 pts received Id/KLH. The last patient was registered in Dec 2003. Among these 89 evaluable pts, 55 were R/R to prior therapy, and 34 were TN. The overall response rate (ORR) following rituximab (assessed at month 3 based on a centralized read of CT scans) was 49% (44/89). Following Id/KLH, the ORR improved to 64% (57/89). The median time for improved response following initiation of Id/KLH treatment was 6.6 months (range 5.8 – 23.4 months) which was consistent with the time required to demonstrate an immune response in those pts tested. Prognostic factors for time to tumor progression (TTP) were evaluated and demonstrated a significant negative relationship for liver involvement (hazard ratio; HR = 9.3, p=0.0017) and 3 or more prior regimens (HR=4.7, p=0.0035). Median TTP has not been reached in the TN group (N=34) and in pts who relapsed after prior chemotherapy (N=26), with an actuarial 18 month progression free survival rate of 69% and 70%, respectively. The group of pts who would be eligible for the ongoing phase 3 randomized registration study (N=71) of rituximab followed by Id/KLH have also not reached median TTP. T-cell responses to both Id and KLH were observed in 80% and 86% of pts respectively (N=15) and were seen after a median of 2 doses of Id/KLH. Likewise, antibody responses to Id and KLH were seen in 13% and 69% respectively (N=23) and developed after a median of 5 to 6 doses of Id/KLH.

Conclusion: Id/KLH, administered following rituximab to pts with FL, appears to result in an increase in the response rate and TTP compared to that reported for rituximab alone. We also observed a high rate of cellular immunity against idiotype following Id/KLH. These data support the design of an ongoing PIII clinical study of Id/KLH following rituximab which excluded pts with poor prognostic indicators.