Expression of inhibitory Fc receptor (FcγRIIB) is a marker of poor response to rituximab monotherapy in follicular lymphoma

Background FcγRIIB promotes rituximab internalisation on various B-cell targets, including in follicular lymphoma, which may lead to reduced efficacy. We analysed diagnostic tumour samples from the SAKK 35/98 trial, which has follow-up data of nearly 10 years to determine the relation of FcγRIIB expression with responses and clinical outcomes after rituximab monotherapy in follicular lymphoma. Methods Available archived tissue samples were stained with an anti-human FcγRIIB antibody. Positive samples were graded into negative/low intensity staining (n=116) or medium/high staining (n=13) by a histopathologist masked to clinical outcomes. Failure-free survival (FFS) was defined as time from first rituximab infusion until failure to achieve complete/partial response at week 12, progression, relapse, a second cancer, or death from any cause. Objective response rate (ORR) was associated with intensity staining levels with Fisher's exact test. All time-to-event endpoints were evaluated with the Kaplan-Meier method; groups were compared with the log-rank test. Hazard ratio (HR) was assessed with Cox proportional hazards models. Findings Patients expressing medium/high levels of FcγRIIB were less likely to respond to rituximab than were those with negative/low levels (ORR 23·1% [95% CI 7·5–50·9] vs 58·6% [49·5–67·2], p=0·02). FFS was higher in the negative/low staining group than in the medium/high staining group (median 8·3 months [95% CI 2·8–13·4, IQR 2·76–28·5] vs 2·8 [not calculable, 2·76–2·76], p=0·002; HR 0·43 [95% CI 0·23–0·78]). There was a non-significant trend towards better overall survival in the low/negative group compared with the medium/high group (median 140·0 months vs 50·0, p=0·13; HR 0·56 [95% CI 0·26–1·20]). Interpretation Elevated FcγRIIB expression level is associated with poor response to rituximab in patients with follicular lymphoma. This group may show better results with non-internalising type II antibodies, a hypothesis for validation in future prospective clinical trials. Funding Cancer Research UK.