Gut Microbiota and B Cell Receptor (BCR) Inhibitors for the Treatment of Chronic Lymphocytic Leukemia: Is Biodiversity Correlated with Clinical Response or Immune-Related Adverse Event Occurrence? A Cross-Sectional Study

肠道微生物群和 B 细胞受体 (BCR) 抑制剂用于治疗慢性淋巴细胞白血病:生物多样性是否与临床反应或免疫相关不良事件发生相关?一项横断面研究

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作者:Valentina Zuccaro, Greta Petazzoni, Irene Mileto, Marta Corbella, Erika Asperges, Paolo Sacchi, Sara Rattotti, Marzia Varettoni, Irene Defrancesco, Patrizia Cambieri, Fausto Baldanti, Luca Arcaini, Raffaele Bruno

Abstract

Several studies have strengthened the link between the gut microbiota (GM) and the response to immunotherapy in patients with tumors, highlighting the potential role of GM as a biomarker of response. Targeted therapies including B-cell receptor (BCR) inhibitors (BCRi) represent the newest approach to the treatment of chronic lymphocytic leukemia (CLL); however, not all patients achieve a satisfactory response, and immune-related adverse events (irAEs) can also impact the efficacy. The aim of the study was to compare GM biodiversity in patients with CLL, treated with BCRi for at least 12 months. Twelve patients were enrolled: 10 patients in the responder group (R) and 2 patients in the non-responder group (NR). We identified seven patients (58.3%) who experienced adverse reactions (AE). Although we did not observe a significant difference across the study population in terms of relative abundance and alpha and beta diversity, we found a differing distribution of bacterial taxa between the analyzed groups. We noted a higher level of the class Bacteroidia and the order Bacteroidales in the R group, and an inversion in the Firmicutes and Bacteroidetes ratio in the AE group. No prior studies have focused on linking GM and response to BCRi in these patients. Although the analyses are preliminary, they provide suggestions to guide future research.

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