Role of the Gut Microbiome in the Outcome of Diffuse Large B-Cell Lymphoma Patients Treated With CAR-T Cell Therapy

Study Overview
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Brief Summary
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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.

Official Title
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Role of the Gut Microbiome in the Outcome of Diffuse Large B-Cell Lymphoma Patients Treated With CAR-T Cell Therapy

Conditions
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Diffuse Large B Cell Lymphoma

Intervention / Treatment
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* Other: Gut microbiome analysis


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. Exclusion Criteria: Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results. Concurrent second malignancy.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: Gut microbiome analysis|Characterization 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|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gut microbiome, CAR T-cell therapy