Gut microbiota role in response to checkpoint inhibitor treatment in patients with relapsed/refractory b‐cell hodgkin lymphoma: an interim analysis from micro‐linf study

Background: Single-agent monoclonal antibodies targeting the immune checkpoint PD-1 (programmed death 1) are an efficient and safe therapeutic option in patients with relapsed/refractory B-cell lymphoma. However, many patients progress or lose response to anti-PD1. Recent studies have highlighted the role of the gut microbiota (GM) in influencing the response to chemo-immunotherapeutic agents. Here we hypothesize that the GM dynamics in B-cell lymphoma patients during anti-PD1 therapy correlate with treatment response. Methods: From December 2017 to December 2020 we enrolled 17 patients (12 with classical Hodgkin lymphoma [cHL] and 5 with primary mediastinal B-cell lymphoma) treated with anti-PD1 due to relapsed/refractory disease. Feces were collected at baseline, before each therapy cycle, at response assessment (during both therapeutic course and follow-up) and for grade ≥2 adverse events, and profiled through Illumina sequencing. At each time point, patients compiled a 7-day weighted food intake record that was analyzed by MètaDieta (METEDA). Results: We report the results of the first 6 patients enrolled, all affected by cHL. Median age was 31 years (range 26-71), 5 patients were female. Five patients were refractory to the last therapy, with a median of previous treatments of 3 (range 3-5). All patients discontinued treatment: 3 due to disease progression; 2 achieved complete remission and interrupted to consolidate with autologous stem cell transplantation; the last due to grade 3 adverse event despite partial remission. The median number of anti-PD1 cycles was 15 (range 7-18). The baseline GM separated from that of age/gender-matched healthy controls, being enriched in the pathobiont Collinsella while depleted of health-associated taxa, e.g. Faecalibacterium, Ruminococcus, Coprococcus and Roseburia (p < 0.05; Figure 1A). The GM dynamics along anti-PD1 treatment were distinct in relation to the therapeutic response, with greater temporal variability of alpha diversity in responders (Figure 1B). The latter consumed more fat and fewer carbohydrates. Keywords: Diagnostic and Prognostic Biomarkers, Immunotherapy No conflicts of interest pertinent to the abstract.