SNPs Do Not Impact Outcomes With Ritixumab/Obinutuzumab in FL, DLBCL

Single-nucleotide polymorphisms (SNPs) have been shown to influence Fcγ receptor (FcγR) activity, but their effect on treatment response is unclear, according to a retrospective analysis. (Blood Adv. 2021;5[15]: 2935-2944).

Thus, Jonathan C. Strefford, BSc, PCCC, PhD, School of Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom, and co-investigators aimed to determine the impact of FcγR genotypes on the efficacy of obinutuzumab or rituximab in combination with chemotherapy in patients with previously untreated advanced follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL).

The analysis extracted genomic DNA from patients enrolled in both the phase 3 GALLIUM (n = 1201) and phase 3 GOYA (n = 1418) trials. Key germline SNPs, including FCGR2A R131H, FCGR3A F158V, and FCGR2B I232T, were assessed for their impact on progression-free survival (PFS).

“As our cohort included many more patients than previously published studies, our analysis provided greater statistical power to establish the clinical importance of these FcγR genotypes,” Dr Strettford et al said.

In both cohorts, no prognostic effect was seen in either FCGR2A or FCGR3A genotypes.

For FL, no significant association was found between PFS and the FCGR2A or FCGR3A genotypes, but FCGR2B was associated with favorable PFS in univariate and multivariate analyses comparing I232T with I232I (hazard ratio [HR], 0.69; 95% CI, 0.51-0.93; P = .01). A more modest association was seen for rituximab-treated patients (univariate: HR, 0.78; 95% CI, 0,54-1.14; P = .21) compared with obinutuzumab-treated patients (univariate: HR, 0.56; 95% CI, 0.34-0.91; P = .02). When comparing the T232T and I232I genotypes, obinutuzumab was associated with a worse prognosis (HR, 2.76; 95% CI, 1.02-7.5; P = .0459).

When comparing T232T with I232I in rituximab-treated patients with DLBCL, the multivariate analysis found FCGR2B was associated with poorer PFS (HR, 4.40; 95% CI, 1.71-11.32; P = .002), however, this genotype is rare (n = 13).

“This study shows that FcγR genotype is not associated with response to rituximab/obinutuzumab plus chemotherapy in treatment-naive patients with advanced FL or DLBCL,” Dr Strefford et al concluded.—Emily Bader