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

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.

The causal relationship between gut microbiota and leukemia: a two-sample Mendelian randomization study

“…For instance, antibiotic treatment that down-regulates the gut microbiota can restore the anti-leukemia efficacy of APO866 (ElMokh et al, 2022). Using B-cell receptor inhibitors (BCRi) as targeted therapy can up-regulate the Bacteroidia levels in CLL patients (Zuccaro et al, 2023). This also seems to underscore the association between the gut microbiota and leukemia.…”

Gut microbiota plays pivotal roles in benign and malignant hematopoiesis

“…Another study found that the gut microbiota of CLL patients treated with B cell receptor (BCR) inhibitors who met the clinical response criteria had a higher number of bacteria from the class Bacteroidia and the order Bacteroidales , they also noted an inversion in the Firmicutes and Bacteroidetes ratio in the patients who undergo adverse effects such as diarrhea. 36 …”