Table 1.
Gut Microbiota Composition and Outcomes in CART-treated Patients
| Publication | Disease | Patients, n (%) | CART, n (%) | AB Exposure, n (%) | Response | Toxicity | |||
|---|---|---|---|---|---|---|---|---|---|
| CR at 3 mo, n (%) | PFS (non-AB vs AB) |
OS (non-AB vs AB) |
CRS (non-AB vs AB) | ICANS (non-AB vs AB) | |||||
| Exposure to AB pre-CART infusion (Smith et al., 2022) | NHL ALL |
137 (60.1) 91 (39.9) |
Anti-CD19, 228 (100): Axi-cel, 72 (31.6) Tisa-cel, 101 (44.3) 19–28z, 55 (24.1) |
No AB, 83 (36.4) Any AB, 145 (63.6) |
Yes, 117 (51.3) No, 111 (48.7) |
NHL-ALL: HR 1.71 (1.12–2.59; P = 0.011) | |||
| NHL: HR 1.29 (0.82–2.01; P = 0.256) | NHL: HR 2.54 (1.41–4.56; P = 0.001) | P = 0.179 | P = 0.013 | ||||||
| P-I-M, 47 (20.6) | NHL-ALL: HR 2.58 (1.68–3.98; P < 0.001) | P = 0.058 | P = 0.023 | ||||||
| NHL: HR 1.83 (1.03–3.27; P = 0.038) | NHL: HR 3.37 (1.77–6.44; P < 0.001) | P = 0.154 | P = 0.002 | ||||||
| ALL: HR 1.96 (1.15–3.35; P = 0.012) | ALL: HR 2.12 (1.2–3.76; P = 0.008) | P = 0.525 | P = 0.254 | ||||||
| Microbiota analysis: NHL ALL |
48 (100) 46 (95.8) 2 (4.2) |
19–28z, 2 (4.2) Axi-cel, 21 (43.8) Tisa-cel, 23 (47.9) Brexu-cel, 2 (4.2) |
Reduced alpha diversity in CART-treated patients (P = 0.0023). Reduced beta diversity in CART-treated patients (P < 0.001). |
Yes, 23 (47.9) No, 25 (52.1) |
High abundance of Ruminococcus, Bacteroides, Faecalibacterium in CR; Akkermansia the top enriched dominant taxon in responders; High abundance of Veillonellales, family Veillonellaceae in NR. |
Blautia, Ruminococcus, Bacteroides, Faecalibacterium associated with the absence of toxicities. | |||
| Microbiota modifications pre- and post-CART in MM (Hu et al., 2022) | MM | 99 (100) | ORR 91 (95)a CR 53 (55.8)a |
||||||
| Microbiota analysis: MM |
81 (81.8) | Anti-BCMA, 81 (100) | Higher alpha diversity in CR vs PR/NR patients; Bifidobacterium, Prevotella, Colllinsella, Sutterella enriched in patients in CR pre- and post-CART; Sutterella associated with prolonged PFS post-CART. |
High abundance of Bifidobacterium and Leuconostoc in patients with CRS. | |||||
| Exposure to ABT pre-CART infusion (Stein-Thoeringer et al., 2023) |
NHL | 172 (100) | Anti-CD19: Axi-cel, 122 (70.9) Tisa-cel, 49 (28.5) Liso-cel, 1 (0.6) |
No AB, 110 (64) Any AB, 62 (36) |
Yes, 82 (47.7) | HR 2.04 (1.38–3.00; P = 0.0009) | HR 2.39 (1.46–3.91; P = 0.0027) | ||
| High-risk ABb, 36 (20.9) | No, 90 (52.3) | HR 3.05 (1.96–4.75; P < 0.0001) | HR 2.99 (1.69–5.29; P = 0.0003) | P = 0.085 | 43.4% vs 63.8% (P = 0.039) | ||||
| Microbiota analysis: NHL | 116 (67.4) | Reduced alpha diversity in high-risk AB-treated patients; High abundance of Prevotella, Veillonella, Enterococcus spp. in high-risk AB-treated patients. |
Pre-CART high abundance of Bacteroides, Ruminococcus, Eubacterium and Akkermansia in CR patients; Bifidobacterium longum associated with response at 6 mo post-CART; High Bacteroides stercoris in NR patients. |
||||||
aResponse at 3 months was assessed in the efficacy analysis cohort of 95 patients.
bHigh-risk AB: piperacillin/tazobactam, meropenem, cefepime, ceftazidime.
AB = antibiotics; ALL = B-cell acute lymphoblastic leukemia; Axi-cel = axicabtagene ciloleucel; Brexu-cel = brexucabtagene autoleucel; CART = chimeric antigen receptor T cell therapy; CR = complete response; CRS = cytokine releasing syndrome; HR = hazard ratio; ICANS = Immune effector cell-associated neurotoxicity syndrome; NHL = non-Hodgkin lymphoma; NR = no response; ORR = overall response rate; OS = overall survival; PFS = progression-free survival; P-I-M = piperacillin/tazobactam, imipenem, meropenem; PR = partial response; Tisa-cel = tisagenlecleucel.