Homozygous A polymorphism of the complement C1qA(276) correlates with prolonged overall survival in patients with diffuse large B cell lymphoma treated with R-CHOP

BACKGROUND: The precise mechanism of action for rituximab (R) is not fully elucidated. Besides antibody-dependent cellular cytotoxicity (ADCC), complements may also play an important role in the clinical response to rituximab-based therapy in diffuse large B cell lymphoma (DLBCL). The purpose of this study was to explore the relationship between C1qA([276]) polymorphism and the clinical response to standard frontline treatment with R-CHOP in DLBCL patients. METHODS: Genotyping for C1qA([276A/G]) was done in 164 patients with DLBCL. 129 patients treated with R-CHOP as frontline therapy (R ≥ 4 cycles) were assessable for the efficacy. RESULTS: Patients with homozygous A were found to have a higher overall response rate than those with heterozygous or homozygous G alleles (97.3% vs. 83.7%,P = 0.068). The complete response rate in patients with homozygous A was statistically higher than that in AG and GG allele carriers (89.2% vs. 51.1%,P = 0.0001). The overall survival of patients with homozygous A was longer than that of the G allele carriers (676 days vs. 497 days, P = 0.023). Multivariate Cox regression analysis showed that C1qA A/A allele was an independent favorable prognostic factor for DLBCL patients treated with R-CHOP as first-line therapy. CONCLUSION: These results suggest that C1qA polymorphism may be a biomarker to predict response to R-CHOP as frontline therapy for DLBCL patients.