Table 3.

Clinical data: microbiome characteristics and IECT outcomes

DiseaseCAR productLevelBacteriaSample sizeCountryOutcome or associationRef
ALL
NHL 
1928z
Axi-cel
Tisa-cel
CTL019
Brexu-cel 
Phylum
Class
Order
Family
Genera
Species 
Bacteroidetes
Clostridia
Bacteroidia
Bacteroidiales
Rumminococcaceae
Bacteroidaceae
Bacteroides
Ruminococcus
Faecalibacterium
Akkermansia
Faecalibacterium prausnitzii
Ruminococcus bromii 
48 United States D 100 CR 90  
  Class
Genera
Species 
Clostridia
Ruminococcus
Faecalibacterium
Faecalibacterium prausnitzii 
  No toxicity  
NHL Axi-cel
Tisa-cel
Liso-cel 
Genera Roseburia
Bifidobacterium
Lactobacillus
Eubacterium 
116 United States
Germany 
Non- or “low-risk” antibiotic exposure  91  
  Species Bifidobacterium longum
Eubacterium eligens
Parabacteroides merdae 
  Alive at 6 mo  
  Species Bacteroides eggerthii
Ruminococcus lactaris
Eubacterium spp. CAG 180
Akkermansia muciniphila
Erysipelatoclostridium ramosum 
  CR based on deterministic ML model  
  Species Lachnospira pectinoschiza
Akkermansia muciniphila 
  Higher CD3 and CD4 T-cell levels  
MM BCMA CAR-T Genera Bifidobacterium
Prevotella
Sutterella
Oscillospira
Paraprevotella
Collinsella
Faecalibacterium
Roseburia
Ruminococcus 
43 China CR 93  
NHL Not specified Genera Faecalibacterium
Bifidobacterium
Ruminococcus 
12    
ALL
NHL 
1928z
Axi-cel
Tisa-cel
CTL019
Brexu-cel 
Order
Family 
Veillonellales
Veillonellaceae 
48 United States D 100 non-CR 90  
NHL Axi-cel
Tisa-cel
Liso-cel 
Species Prevotella
Veillonella
Enterococcus 
116 United States
Germany 
“High-risk” antibiotic exposure  91  
  Species Bacteroides stercoris   Nonresponse based on deterministic ML model  
  Species Bacteroides uniformis
Bacteroides ovatus
Blautia spp.
Faecalibacterium prausnitzii 
  Lower CD3 and CD8 T-cell levels  
ALL Not specified Genera Bifidobacterium
Roseburia
Collinsella 
23 China Nonresponse 93  
MM BCMA CAR-T Genera Bifidobacterium
Leuconostoc 
43  Severe CRS  
DiseaseCAR productLevelBacteriaSample sizeCountryOutcome or associationRef
ALL
NHL 
1928z
Axi-cel
Tisa-cel
CTL019
Brexu-cel 
Phylum
Class
Order
Family
Genera
Species 
Bacteroidetes
Clostridia
Bacteroidia
Bacteroidiales
Rumminococcaceae
Bacteroidaceae
Bacteroides
Ruminococcus
Faecalibacterium
Akkermansia
Faecalibacterium prausnitzii
Ruminococcus bromii 
48 United States D 100 CR 90  
  Class
Genera
Species 
Clostridia
Ruminococcus
Faecalibacterium
Faecalibacterium prausnitzii 
  No toxicity  
NHL Axi-cel
Tisa-cel
Liso-cel 
Genera Roseburia
Bifidobacterium
Lactobacillus
Eubacterium 
116 United States
Germany 
Non- or “low-risk” antibiotic exposure  91  
  Species Bifidobacterium longum
Eubacterium eligens
Parabacteroides merdae 
  Alive at 6 mo  
  Species Bacteroides eggerthii
Ruminococcus lactaris
Eubacterium spp. CAG 180
Akkermansia muciniphila
Erysipelatoclostridium ramosum 
  CR based on deterministic ML model  
  Species Lachnospira pectinoschiza
Akkermansia muciniphila 
  Higher CD3 and CD4 T-cell levels  
MM BCMA CAR-T Genera Bifidobacterium
Prevotella
Sutterella
Oscillospira
Paraprevotella
Collinsella
Faecalibacterium
Roseburia
Ruminococcus 
43 China CR 93  
NHL Not specified Genera Faecalibacterium
Bifidobacterium
Ruminococcus 
12    
ALL
NHL 
1928z
Axi-cel
Tisa-cel
CTL019
Brexu-cel 
Order
Family 
Veillonellales
Veillonellaceae 
48 United States D 100 non-CR 90  
NHL Axi-cel
Tisa-cel
Liso-cel 
Species Prevotella
Veillonella
Enterococcus 
116 United States
Germany 
“High-risk” antibiotic exposure  91  
  Species Bacteroides stercoris   Nonresponse based on deterministic ML model  
  Species Bacteroides uniformis
Bacteroides ovatus
Blautia spp.
Faecalibacterium prausnitzii 
  Lower CD3 and CD8 T-cell levels  
ALL Not specified Genera Bifidobacterium
Roseburia
Collinsella 
23 China Nonresponse 93  
MM BCMA CAR-T Genera Bifidobacterium
Leuconostoc 
43  Severe CRS  

ALL, acute lymphoblastic leukemia; axi-cel; axicabtagene ciloleucel; brexu-cel, brexucabtagene autoleucel; liso-cel, lisocabtagene maraleucel; MM, multiple myeloma; tisa-cel, tisagenlecleucel.

“High-risk” antibiotics defined by study as meropenem, cefepime, ceftazidime, and piperacillin-tazobactam. “Low-risk” antibiotic exposure defined by study as exposure to any antibiotic not in the “high-risk” group.91 

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