Idiotype vaccine therapy of follicular lymphoma in first remission: Association of t(14;18) and disease free survival in a phase II cohort

Abstract

7582 Background: A single-arm Phase 2 study (Nature Med 5:1171–7,1999), evaluated the ability of tumor-specific idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) administered with granulocyte-monocyte colony-stimulating factor - GM-CSF (BiovaxID vaccine) to induce complete remission (CR) and molecular remission (MR) in follicular NHL patients in first CR after chemotherapy. We reported (ASH 2005, Abstr 2441) that at 9.2 years follow-up, disease free survival (DFS) and overall survival (OS) were 45% and 95%, respectively; median DFS was 8.0 years. Previous studies indicated that the t(14;18) chromosomal translocation is associated with follicular NHL. We tested the hypothesis that absence of t(14;18) in peripheral blood (PB) of patients after Id vaccination is predictive of DFS. Methods: A 20-patient cohort in first CR treated with the vaccine was evaluated. t(14;18)- (MR) is defined as <1 t(14;18)+ cell in 105 cells using PCR of the MBR breakpoint cluster on DNA from tumor biopsies or PB. Of the 20 patients, 11 had t(14;18)+ tumors and PB before chemotherapy. Following chemotherapy all 11 patients continued to have t(14;18)+ PB despite being in CR. However, at 1 month following final vaccine treatment, 8 of these patients had converted to t(14;18)- . In this ad hoc analysis, the proportion of patients remaining in DFS was stratified by t(14;18) status; Kaplan-Meier analysis compared median DFS of patients across t(14;18) status following vaccination. Results: At median follow-up of 9.2 years, 55% of patients had clinically relapsed. Although not statistically significant, of the 17 patients t(14;18)- post-vaccine, only 47.1% had clinically relapsed while 100% of the 3 t(14;18)+ patients had relapsed [Chi-square test; P=0.089]. Median DFS in t(14;18)+ patients was 60 months (5.0 years) and had not yet been reached in t(14;18)- patients at 91 months (7.6 years) [Log-rank test; P=0.069]. Conclusions: These data show a possible association between t(14;18) negativity following vaccine and prolonged DFS. Additional follow-up on these patients is needed, as well as similar analyses in other cohorts, to further explore this association. [Table: see text]