Intestinal Microbiota Composition Prior to CAR T Cell Infusion Correlates with Efficacy and Toxicity

ConclusionWe demonstrate that our subset of patients had diverse microbial composition prior to receiving CAR T cell therapy despite the fact that many of them were heavily pre-treated. Additionally, we observe the abundance of the family Lachnospiraceae in the patients who achieved a CR and those who experienced toxicity. Many Lachnospiraceae are butyrate producers, whose presence has been found to be protective against Clostridium difficile infection in recipients of allogeneic hematopoietic cell transplant but whose abundance is lower in colon cancer. Conversely, we observe an abundance of the family Peptostreptococcaceae in patients who did not achieve a CR or who did experience toxicity. Peptostreptococcaceae has been found to be more abundant in the intestines of patients with colon cancer. Of note, the intestinal micriobiota that we identify are not congruent with the specific bacteria that have been found to promote anti-tumor immunity to checkpoint blockade. Our data suggests a role for the intestinal microbiota in mediating the response to CAR T cells and proposes that the baseline microbial composition may correlate with efficacy and toxicity. Further studies will investigate biochemical mechanisms to understand the interplay of the intestinal microbiota and the immune system to improve patient outcomes following CAR T cell therapy.DisclosuresPark: Adaptive Biotechnologies: Consultancy; Juno Therapeutics: Consultancy, Research Funding; Novartis: Consultancy; AstraZ...

Source: Blood - November 21, 2018 Category: Hematology Authors: Smith, M., Littmann, E. R., Slingerland, J. B., Clurman, A., Slingerland, A. E., Taur, Y., Schluter, J., Park, J. H., O'Cearbhaill, R., Mailankody, S., Smith, E. L., Palomba, M. L., Yeku, O., Peled, J. U., Halton, E., Diamonte, C., Chan, J., Hall, M., Ana Tags: 801. Gene Therapy and Transfer: Poster II Source Type: research