Multivariable analysis of risk factors associated with infection-related complication during day 0-100 after CAR T-cell therapy
| Variable . | Overall infection . | Bacterial infection . | Viral infection . | Fungal infection . | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n . | Event . | HR (95% CI) . | P value . | n . | Event . | HR (95% CI) . | P value . | n . | Event . | HR (95% CI) . | P value . | n . | Event . | HR (95% CI) . | P value . | |
| Age (decades)∗ | 3296 | 695 | 1.067 (1.006-1.131) | .030 | 3304 | 439 | 1.117 (1.037-1.203) | .003 | NA | NA | NA | NA | NA | NA | NA | NA |
| KPS | <.001 (3 df) | <.001 | <.0001 (3 df) | .014 (3 df) | ||||||||||||
| 90-100 | 1344 | 207 | Ref | Ref | 1345 | 125 | Ref | Ref | 1349 | 89 | Ref | Ref | 1349 | 20 | Ref | Ref |
| 80 | 976 | 237 | 1.644 (1.366-1.979) | <.001 | 980 | 134 | 1.466 (1.152-1.864) | .002 | 979 | 114 | 1.867 (1.416-2.461) | <.001 | 981 | 25 | 1.708 (0.968-3.014) | .065 |
| <80 | 627 | 196 | 2.089 (1.716-2.544) | <.001 | 629 | 138 | 2.343 (1.840-2.984) | <.001 | 633 | 89 | 2.194 (1.627-2.960) | <.001 | 635 | 28 | 2.347 (1.344-4.099) | .003 |
| Missing | 349 | 75 | 1.472 (1.129-1.920) | .004 | 350 | 42 | 1.320 (0.937-1.861) | .113 | 352 | 39 | 1.746 (1.196-2.548) | .004 | 353 | 13 | 2.467 (1.219-4.994) | .012 |
| Baseline infection history | .004 (2 df) | .006 (2 df) | .002 (2 df) | |||||||||||||
| No | 2997 | 636 | Ref | Ref | 3004 | 388 | Ref | Ref | NA | NA | NA | NA | 3017 | 74 | Ref | Ref |
| Yes | 130 | 43 | 1.707 (1.246-2.338) | .001 | 131 | 30 | 1.831 (1.266-2.650) | .001 | NA | NA | NA | NA | 132 | 10 | 3.305 (1.675-6.520) | .001 |
| Missing | 169 | 36 | 0.972 (0.694-1.363) | .870 | 169 | 21 | 0.956 (0.621-1.473) | .840 | NA | NA | NA | NA | 169 | 2 | 0.656 (0.207-2.077) | .474 |
| No. of lines of previous therapy | .017 (2 df) | .006 (2 df) | ||||||||||||||
| 1-2 | 977 | 177 | Ref | Ref | NA | NA | NA | NA | 981 | 76 | Ref | Ref | NA | NA | NA | NA |
| ≥3 | 2234 | 521 | 1.270 (1.073-1.503) | .005 | NA | NA | NA | NA | 2247 | 251 | 1.417 (1.095-1.834) | .008 | NA | NA | NA | NA |
| Missing | 85 | 17 | 1.021 (0.616-1.695) | .934 | NA | NA | NA | NA | 85 | 4 | 0.536 (0.194-1.477) | .228 | NA | NA | NA | NA |
| CAR T-cell product | ||||||||||||||||
| Tisa-cel | 538 | 82 | Ref | Ref | 539 | 44 | Ref | Ref | NA | NA | NA | NA | NA | NA | NA | NA |
| Axi-cel | 2758 | 633 | 1.483 (1.177-1.867) | .001 | 2765 | 395 | 1.800 (1.321-2.453) | <.001 | NA | NA | NA | NA | NA | NA | NA | NA |
| Grade 3-5 CRS† | ||||||||||||||||
| No | Ref | Ref | Ref | Ref | Ref | Ref | Ref | Ref | ||||||||
| Yes | 1.762 (1.385-2.241) | <.001 | 1.898 (1.422-2.534) | <.001 | 1.546 (1.076-2.222) | .018 | 2.555 (1.418-4.603) | .002 | ||||||||
| Grade 3-5 ICANS† | ||||||||||||||||
| No | Ref | Ref | Ref | Ref | Ref | Ref | Ref | Ref | ||||||||
| Yes | 1.707 (1.408-2.070) | <.001 | 1.733 (1.356-2.214) | <.001 | 1.488 (1.125-1.968) | .005 | 2.629 (1.580-4.375) | <.001 | ||||||||
| Neutrophil recovery | ||||||||||||||||
| Yes | Ref | Ref | NA | NA | Ref | Ref | Ref | Ref | ||||||||
| No | 1.350 (1.075-1.694) | .01 | NA | NA | 1.471 (1.037-2.085) | .030 | 2.318 (1.362-3.945) | .001 | ||||||||
| Variable . | Overall infection . | Bacterial infection . | Viral infection . | Fungal infection . | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| n . | Event . | HR (95% CI) . | P value . | n . | Event . | HR (95% CI) . | P value . | n . | Event . | HR (95% CI) . | P value . | n . | Event . | HR (95% CI) . | P value . | |
| Age (decades)∗ | 3296 | 695 | 1.067 (1.006-1.131) | .030 | 3304 | 439 | 1.117 (1.037-1.203) | .003 | NA | NA | NA | NA | NA | NA | NA | NA |
| KPS | <.001 (3 df) | <.001 | <.0001 (3 df) | .014 (3 df) | ||||||||||||
| 90-100 | 1344 | 207 | Ref | Ref | 1345 | 125 | Ref | Ref | 1349 | 89 | Ref | Ref | 1349 | 20 | Ref | Ref |
| 80 | 976 | 237 | 1.644 (1.366-1.979) | <.001 | 980 | 134 | 1.466 (1.152-1.864) | .002 | 979 | 114 | 1.867 (1.416-2.461) | <.001 | 981 | 25 | 1.708 (0.968-3.014) | .065 |
| <80 | 627 | 196 | 2.089 (1.716-2.544) | <.001 | 629 | 138 | 2.343 (1.840-2.984) | <.001 | 633 | 89 | 2.194 (1.627-2.960) | <.001 | 635 | 28 | 2.347 (1.344-4.099) | .003 |
| Missing | 349 | 75 | 1.472 (1.129-1.920) | .004 | 350 | 42 | 1.320 (0.937-1.861) | .113 | 352 | 39 | 1.746 (1.196-2.548) | .004 | 353 | 13 | 2.467 (1.219-4.994) | .012 |
| Baseline infection history | .004 (2 df) | .006 (2 df) | .002 (2 df) | |||||||||||||
| No | 2997 | 636 | Ref | Ref | 3004 | 388 | Ref | Ref | NA | NA | NA | NA | 3017 | 74 | Ref | Ref |
| Yes | 130 | 43 | 1.707 (1.246-2.338) | .001 | 131 | 30 | 1.831 (1.266-2.650) | .001 | NA | NA | NA | NA | 132 | 10 | 3.305 (1.675-6.520) | .001 |
| Missing | 169 | 36 | 0.972 (0.694-1.363) | .870 | 169 | 21 | 0.956 (0.621-1.473) | .840 | NA | NA | NA | NA | 169 | 2 | 0.656 (0.207-2.077) | .474 |
| No. of lines of previous therapy | .017 (2 df) | .006 (2 df) | ||||||||||||||
| 1-2 | 977 | 177 | Ref | Ref | NA | NA | NA | NA | 981 | 76 | Ref | Ref | NA | NA | NA | NA |
| ≥3 | 2234 | 521 | 1.270 (1.073-1.503) | .005 | NA | NA | NA | NA | 2247 | 251 | 1.417 (1.095-1.834) | .008 | NA | NA | NA | NA |
| Missing | 85 | 17 | 1.021 (0.616-1.695) | .934 | NA | NA | NA | NA | 85 | 4 | 0.536 (0.194-1.477) | .228 | NA | NA | NA | NA |
| CAR T-cell product | ||||||||||||||||
| Tisa-cel | 538 | 82 | Ref | Ref | 539 | 44 | Ref | Ref | NA | NA | NA | NA | NA | NA | NA | NA |
| Axi-cel | 2758 | 633 | 1.483 (1.177-1.867) | .001 | 2765 | 395 | 1.800 (1.321-2.453) | <.001 | NA | NA | NA | NA | NA | NA | NA | NA |
| Grade 3-5 CRS† | ||||||||||||||||
| No | Ref | Ref | Ref | Ref | Ref | Ref | Ref | Ref | ||||||||
| Yes | 1.762 (1.385-2.241) | <.001 | 1.898 (1.422-2.534) | <.001 | 1.546 (1.076-2.222) | .018 | 2.555 (1.418-4.603) | .002 | ||||||||
| Grade 3-5 ICANS† | ||||||||||||||||
| No | Ref | Ref | Ref | Ref | Ref | Ref | Ref | Ref | ||||||||
| Yes | 1.707 (1.408-2.070) | <.001 | 1.733 (1.356-2.214) | <.001 | 1.488 (1.125-1.968) | .005 | 2.629 (1.580-4.375) | <.001 | ||||||||
| Neutrophil recovery | ||||||||||||||||
| Yes | Ref | Ref | NA | NA | Ref | Ref | Ref | Ref | ||||||||
| No | 1.350 (1.075-1.694) | .01 | NA | NA | 1.471 (1.037-2.085) | .030 | 2.318 (1.362-3.945) | .001 | ||||||||
Center effects were found to be significant by score test (P < .001) for all outcomes. Therefore, marginal Cox regression models were fitted to account for these effects.
df, degrees of freedom; NA, not applicable; Ref, reference.
Age was treated as a continuous variable.
CRS, ICANS onset, and neutrophil recovery were treated as time-dependent covariates.