Gut microbiome data can predict response to CAR-T for multiple myeloma
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Researchers developed a highly accurate model that can predict which patients will achieve complete response to chimeric antigen receptor T-cell therapy for multiple myeloma.
The model is based on clinical and metabolic data plus gut microbiome composition genomic analysis, according to findings presented at European Society for Blood and Marrow Transplantation-European Hematology Association 5th European CAR T-cell Meeting.
Background
Previous study results suggested the gastrointestinal microbiome can impact T-cell phenotype and function, in addition to modulating the body's antitumor immune response, according to Mireia Uribe-Herranz, PhD, an assistant researcher at August Pi i Sunyer Biomedical Research Institute (IDIBAPS) in Barcelona, Spain.
"Our hypothesis in this study was that gastrointestinal microbiota could influence the efficacy of CAR T-cell therapy [for] patients with multiple myeloma,” she said during a presentation.
Methodology
CARTBCMA-HCB-01 — a Spain-based multicenter trial — evaluated the safety and efficacy of ARI-0002h, an investigational B-cell maturation-directed CAR T-cell therapy for adults with relapsed or refractory multiple myeloma. All patients had received treatment with a proteasome inhibitor, an immunomodulatory drug and an anti-CD38 monoclonal antibody.
Study investigators collected stool samples from 28 patients (median age, 60.5 years; range, 28-74; 61% men) after apheresis but at least 5 days before CAR-T infusion. They also took blood samples 28 and 100 days after infusion.
Researchers used 16S rRNA gene sequencing to determine gastrointestinal microbiota composition for each patient. They also collected clinical and CAR-T production data from all patients.
Key findings
Investigators reported a 100% overall response rate, including a 53.6% initial complete remission rate.
Eighty-six percent of patients developed cytokine release syndrome; however, no reported cases of grade 3 or higher CRS occurred during the study.
Researchers reported no incidence of neurotoxicity.
Gut microbiome analysis showed heterogenous bacterial composition, including a total of 67 different families, the most frequent of which were Lachnospiraceae, Streptococcaceae and Ruminococcaceae.
Patients who achieved a complete response to therapy had a higher alpha diversity of bacterial composition 100 days after infusion than those who had a partial response.
The presence of the Acidaminococcaceae family in gut microbiota correlated with complete response to therapy at day 100 after infusion.
The final model included 10 metagenomic and metabolic variables and had an area under the curve of 0.98.
The researchers also developed a highly accurate eight-variable model to predict evolution of response to therapy (area under the curve = 0.986) based on gut microbiome.
Clinical implications
The high accuracy of the predictive model suggests an association between compositional differences in gastrointestinal microbiota and clinical responses to treatment using B-cell maturation antigen-directed CAR-T, according to Uribe-Herranz.
The “predictive model with high accuracy” can differentiate CAR-T recipients likely to have a complete response at day 100 after infusion, she said. This includes a model that can predict which patients are likely to transition from partial to complete response between days 28 and 100 after infusion.
Collapse
Uribe-Herranz M, et al. Abstract BA03-2. Presented at: European Society for Blood and Marrow Transplantation-European Hematology Association 5th European CAR T-cell Meeting; Feb. 9-11, 2023; Rotterdam, Netherlands.
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