创作:aluba 审核:aluba 2022年04月01日
  • 纳入228名接受CAR-T细胞治疗的患者(137名NHL、91名ALL),约60%在治疗前使用过抗生素;
  • 治疗前4周内的抗生素治疗与较短的总生存期及较高的神经毒性风险相关;
  • 在包含48名患者的前瞻性队列中,患者治疗前的粪便菌群与健康对照有显著差异;
  • 患者治疗前的粪便菌群中的特定细菌分类群及代谢通路与临床结局相关,更高的瘤胃球菌属、拟杆菌属及粪杆菌属的丰度与治疗100天后的完全应答相关。
接受CD19 CAR-T细胞治疗后,约60%的患者可能复发,而约80%的患者可能经历CAR介导的毒性。Nature Medicine上发表的一项队列研究结果,发现CAR-T治疗前的抗生素使用与较差的预后及毒性相关,并鉴定出了与CAR-T治疗后应答相关的特定肠道细菌分类群及代谢通路。
Nature Medicine [IF:87.241]

Gut microbiome correlates of response and toxicity following anti-CD19 CAR T cell therapy

肠道菌群与CD19 CAR-T细胞治疗的应答及毒性相关


2022-03-14, Article

Abstract & Authors:展开

Anti-CD19 chimeric antigen receptor (CAR) T cell therapy has led to unprecedented responses in patients with high-risk hematologic malignancies. However, up to 60% of patients still experience disease relapse and up to 80% of patients experience CAR-mediated toxicities, such as cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome. We investigated the role of the intestinal microbiome on these outcomes in a multicenter study of patients with B cell lymphoma and leukemia. We found in a retrospective cohort (n = 228) that exposure to antibiotics, in particular piperacillin/tazobactam, meropenem and imipenem/cilastatin (P-I-M), in the 4 weeks before therapy was associated with worse survival and increased neurotoxicity. In stool samples from a prospective cohort of CAR T cell recipients (n = 48), the fecal microbiome was altered at baseline compared to healthy controls. Stool sample profiling by 16S ribosomal RNA and metagenomic shotgun sequencing revealed that clinical outcomes were associated with differences in specific bacterial taxa and metabolic pathways. Through both untargeted and hypothesis-driven analysis of 16S sequencing data, we identified species within the class Clostridia that were associated with day 100 complete response. We concluded that changes in the intestinal microbiome are associated with clinical outcomes after anti-CD19 CAR T cell therapy in patients with B cell malignancies.

First Authors:
Melody Smith

Correspondence Authors:
Andrea Facciabene,Marcel R M van den Brink,Marco Ruella

All Authors:
Melody Smith,Anqi Dai,Guido Ghilardi,Kimberly V Amelsberg,Sean M Devlin,Raymone Pajarillo,John B Slingerland,Silvia Beghi,Pamela S Herrera,Paul Giardina,Annelie Clurman,Emmanuel Dwomoh,Gabriel Armijo,Antonio L C Gomes,Eric R Littmann,Jonas Schluter,Emily Fontana,Ying Taur,Jae H Park,Maria Lia Palomba,Elizabeth Halton,Josel Ruiz,Tania Jain,Martina Pennisi,Aishat Olaide Afuye,Miguel-Angel Perales,Craig W Freyer,Alfred Garfall,Shannon Gier,Sunita Nasta,Daniel Landsburg,James Gerson,Jakub Svoboda,Justin Cross,Elise A Chong,Sergio Giralt,Saar I Gill,Isabelle Riviere,David L Porter,Stephen J Schuster,Michel Sadelain,Noelle Frey,Renier J Brentjens,Carl H June,Eric G Pamer,Jonathan U Peled,Andrea Facciabene,Marcel R M van den Brink,Marco Ruella