Circulating tumor DNA for comprehensive noninvasive monitoring of lymphoma treated with ibrutinib plus nivolumab.

To advance the use of circulating tumor DNA (ctDNA) applications, their broad clinical validity must be tested in different treatment settings, including targeted therapies. Using the prespecified longitudinal systematic collection of plasma samples in the phase 1/2a LYM1002 trial (registered on www.clinicaltrials.gov as NCT02329847), we tested the clinical validity of ctDNA for baseline mutation profiling, residual tumor load quantification, and acquisition of resistance mutations in patients with lymphoma treated with ibrutinib+nivolumab. Inclusion criterion for this ancillary biological study was the availability of blood collected at baseline and cycle 3, day 1. Overall, 172 ctDNA samples from 67 patients were analyzed by the LyV4.0 ctDNA Cancer Personalized Profiling Deep Sequencing Assay. Among baseline variants in ctDNA, only TP53 mutations (detected in 25.4% of patients) were associated with shorter progression-free survival; clones harboring baseline TP53 mutations did not disappear during treatment. Molecular response, defined as a >2-log reduction in ctDNA levels after 2 cycles of therapy (28 days), was achieved in 28.6% of patients with relapsed diffuse large B-cell lymphoma who had ≥1 baseline variant and was associated with best response and improved progression-free survival. Clonal evolution occurred frequently during treatment, and 10.3% new mutations were identified after 2 treatment cycles in nonresponders. PLCG2 was the topmost among genes that acquired new mutations. No patients acquired the C481S BTK mutation implicated in resistance to ibrutinib in CLL. Collectively, our results provide the proof of concept that ctDNA is useful for noninvasive monitoring of lymphoma treated with targeted agents in the clinical trial setting.

Helicobacter spp. in Experimental Models of Colitis.

The colonization of body surfaces, notably of the intestine, by a complex microbiota is generally highly mutualistic, where vital functions are provided by the commensal microbiota to the host, including the synthesis of vitamins, the degradation of complex polysaccharides into small chain fatty acids (which are essential for the maintenance of the intestinal epithelial barrier), and, finally, the outcompetition of pathogens that accidentally gain access to the body ("colonization resistance") (Chow et al. 2011; Backhed 2005). However, under certain conditions, such as changes of environmental factors in a genetically predisposed host, some of these normally symbiotic bacteria may act as pathogens and induce pathologies. Hence, the term "pathobionts" was coined for these bacterial species with ambiguous biological properties (Round et al. 2009).