Despite impressive outcomes in selected patients, significant heterogeneity in clinical response to CAR-T cell therapy remains. The gut microbiome (GM) has recently emerged as one of the key modifiable factors of prognosis and response to treatment in cancer patients, with high-diversity profiles rich in health-associated taxa while poor in pathobionts generally associated with better response and longer survival. Currently, it is unknown if GM also modulates anti-tumor responses to CAR-T cells and related toxicities in lymphomas.
Age ≥18 years.
Patients affected by histologically confirmed DLBCL.
Patients amenable for CAR-T cell therapy as for clinical approved indication (commercial products).
Patients must provide written informed consent.
Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results.
Concurrent second malignancy.
Up to 90 relapsed/refractory diffuse large B-cell lymphoma adult (≥18 years) patients undergoing CAR-T cell therapy will be enrolled over 3 years, treated and followed up with fecal sample collection until 18 months after CAR-T cell infusion.
Cohort
Prospective
Gut microbiome analysis
Other interventionCharacterization of the compositional and functional modifications of gut microbiome in patients affected by lymphoma undergoing therapy with CAR-T cells from baseline until the restaging after 18 months from the CAR-T cell infusion
Characterization of GM heterogeneity (taxa) in diffuse large B-cell lymphoma patients undergoing CAR-T cell therapy.
Characterization of the compositional and functional modifications of GM in patients affected by lymphoma undergoing therapy with CAR-T cells from baseline until the restaging after 18 months from the CAR-T cell infusion. GM profiling will be achieved by next-generation sequencing approaches, including 16S rRNA gene-based sequencing for diversity and compositional structure, and shotgun metagenomics for species-level and functional insights, including information on eukaryotes and viruses.
Correlation between GM and CAR-T cell therapy outcomes in terms of response, toxicity and disease control.
Define novel GM signatures that relate to more favorable response to the CAR-T treatment and/or reducing the occurrence of side effects.
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University of Bologna
Lead sponsor
Associazione Italiana per la Ricerca sul Cancro
Collaborator
IRCCS Azienda Ospedaliero-Universitaria di Bologna
Collaborator
