FcγR IIIa polymorphism and anti-idiotype humoral immune response predict clinical outcome in follicular lymphoma patients receiving idiotypic vaccination

Abstract

6503 Background: The Ig idiotype (Id) expressed by B cell lymphoma is a target for immunotherapy. Id vaccination (Vac) induces humoral and/or cellular anti-Id immune response (IR). However, the clinical impact of these anti-Id IR is unknown. We have recently found that IgG Fc receptor (FcγR) polymorphisms predict the response to rituximab, due to their role in the antibody-dependent cellular cytotoxicity. We tested if anti-Id IR or FcγR polymorphisms have clinical impact in patients who received Id Vac. Methods: We analyzed 155 follicular lymphoma patients who had Id Vac between 1988 and 2001 at Stanford Medical Center. All patients received induction chemotherapy followed by Id Vac. The FcγRIIa 131 H/R and FcγRIIIa 158 V/F polymorphism was determined. Results: Humoral and cellular anti-Id IR were found after Id Vac in 51 (33%) and 35 (23%) patients, respectively. The humoral IR was associated with longer freedom from progression (FFP) after induction chemotherapy/Id Vac (humoral IR, 6.23 yrs vs other, 2.66 yrs, p=0.006). The cellular IR had no impact on the FFP. Patients with FcγRIIIa V/V genotype enjoyed longer FFP than those with V/F or F/F (median time to progression: V/V, 8.21 yrs vs V/F, 2.66 yrs, p=0.002; vs F/F, 2.89 yrs, p=0.021). In contrast, the FcγRIIa polymorphism had no impact on FFP. Multi-variant analysis using the Cox Proportional Hazards Model showed that V/V genotype and humoral IR were two independent positive predictors for disease free survival, and stage IV disease was a negative predictor, while FcγRIIa polymorphism, cellular IR, gender, age, B symptoms or time from diagnosis to therapy had no impact. The relative benefit was 4.12 (95% CI, 1.83–9.27, p=0.0006) for V/V genotype and 2.45 (95% CI, 1.50–4.00, p=0.0004) for humoral IR. Conclusions: There was clinical benefit of humoral anti-Id IR in a large group of patients vaccinated with Id. We also identified the clinical importance of FcγRIIIa polymorphism in these patients probably due to its role in anti-Id antibody-mediated cytotoxicity. No significant financial relationships to disclose.