Interluekin-10 (IL-10) Promoter Gene Polymorphism (−819*C) Associated with Poor Clinical Outcome in DLBCL Patients Treated with R (Rituximab)-CHOP Regimen as a First Line.

IL-10 is an anti-inflammatory cytokine inhibiting T_h1 functions, which may facilitate development of NHL by supporting tumor escape from the immune response. Among the various IL-10 promotor genes, the IL-10-1082G, −819C and −592C alleles were reported to be associated with high serum IL-10 level and there were a few reports about their roles in treatment outcome of DLBCL patients. In the present study, we studied the frequency of these 3 alleles and their influence to the clinical outcome in DLBCL patients treated with standardized regimen; 8 cycles of R (375 mg/m² on day 1 of each cycle)-CHOP every 3 weeks or 4 cycles of R-CHOP with involved field radiotherapy. 60 patients with newly diagnosed DLBCL were included and all of them represented CD20 positivity. At diagnosis, median age was 60 (19~95) and 30 (57.7%), 13 (25.0), 7 (13.5%) and 2 (3.8%) patients belonged to the low, low-intermediate, high-intermediate and high risk group according to IPI reports, retrospectively. Of total 60 patients, 9 (15%), 23 (38.3%) and 27 (45%) were found to carry IL-10-1082G, −819C and −592C alleles, retrospectively. As compared with -1082AA genotype, -1082G allele (GA/GG) failed to show better outcome (eg. higher CR or longer progression-free survival, PFS) in interim results after 4 cycles of treatment. On the other hands, after completion of 4 R-CHOP, patients with −819C allele (TC/CC) showed significantly lower response rate (CR or PR) than in patients carrying -819TT (82.6% vs. 100%, p<0.05). Furthermore, the progression-free survival (PFS) was significantly shorter in patients carrying −819C allele than TT genotype (18.4 ms. vs. 26.9 ms. p<0.05). Patients with −592C allele (AC/CC) also showed lower interim response rate than with AA genotype (85.2% vs. 100%, p<0.05). PFS also decreased in −592C allele compared with AA genotype (18.8 ms. vs. 26.8 ms., p<0.05). In multivariate analysis including IPI, stage, IL-10-1082G, −819C and −592C allele frequencies, −819C allele remained as an independent prognostic factor predicting shorter PFS (RR=4.3, p<0.05). Additionally, in a haplotype analysis, there was a trend of longer PFS in patients carrying ATA/ATA than in other haplotypes but there was no statistical significance (p=0.08). As is well known, after introduction of rituximab in the treatment regimen, patients with DLBCL have been shown better treatment outcome than before. However, it is still a matter of problem to find and to manage the patients with refractory or progressive disease despite of these reinforced regimens. This study suggests that the detection of IL-10 gene promoter polymorphism such as −819C allele helps us to predict the prognosis and to establish a stratified treatment plan in DLBCL patients.