Comparison of our validation cohort to the CAR-HEMATOTOX development cohort, including demographics, disease factors, and postinfusion adverse events
| Cohort characteristics . | Validation cohort N = 109 . | Development cohort N = 248 . | P value∗ . |
|---|---|---|---|
| Age, y (range) | 64 (57-69) | 63 (19-83) | |
| Disease entity | |||
| Nontransformed lymphoma (DLBCL, PMBCL) | 89 (82%) | 194 (78%) | .54 |
| Transformed lymphoma (trFL, trMCL, trMALT, trCLL, trHL) | 20 (18%) | 54 (22%) | |
| CAR-HEMATOTOX score ≥2 (HThigh) | 44 (40%) | 133 (54%) | .02 |
| LDH (median, IQR) | 236 (191-321) | 281.5 (260-318) | |
| CAR-T product | |||
| Axi-cel | 64 (59%) | 138 (56%) | .59 |
| Tisa-cel | 45 (41%) | 110 (44%) | |
| Prior autologous SCT | 34 (31%) | 68 (27%) | .48 |
| CRS (all-grade) | 94 (86%) | 209 (85%) | .63 |
| CRS (grade ≥3) | 5 (5%) | 24 (9%) | .10 |
| ICANS (all-grade) | 39 (36%) | 110 (39%) | .13 |
| ICANS (grade ≥3) | 12 (11%) | 39 (15%) | .24 |
| Tocilizumab use | 76 (70%) | 140 (56%) | .02 |
| Median cumulative tocilizumab during index admission, mg, (IQR) | 800 (0-1600) | NR | N/A |
| Corticosteroid use | 52 (48%) | 99 (40%) | .17 |
| Median cumulative steroid exposure during index admission, mg, (IQR of dexamethasone equivalency) | 0 (0-42) | NR | N/A |
| Prolonged corticosteroids (≥9 d) | 9 (8%) | 35 (14%) | .001 |
| ICAHT (day 0-30) | |||
| Grade 0-2 | 85 (78%) | Not available | N/A |
| Grade ≥3 | 24 (22%) | 70 (28%) | .16 |
| G-CSF | 29 (27%) | 106 (43%) | .004 |
| ICU admission | 17 (16%) | 37 (15%) | .87 |
| Infections events day 0-90 | 39 in 31 patients (28%) | 193 in 112 patients (45%) | .003 |
| Grade ≥3 infection events day 0-90 | 21 in 11 patients (11%) | 72 in 62 patients (25%) | .0013 |
| Microbiologically confirmed infections | 30 (77% of infection events) | 86 (45% of infection events) | N/A |
| Bacterial | 14 in 11 patients (11%) | 64 patients (26%) | .35§ |
| Bacterial (grade ≥3) | 8 in 5 patients (5%)† | 37 patients (15%)‡ | |
| Viral | 11 in 10 patients (8%) | 34 in 26 patients (10.5%) | |
| Fungal | 5 in 5 patients (5%) | 24 in 20 patients (8.2%) | |
| Clinically-defined infections | 9 in 9 patients (23%) | 107 events | .0002§ |
| Cohort characteristics . | Validation cohort N = 109 . | Development cohort N = 248 . | P value∗ . |
|---|---|---|---|
| Age, y (range) | 64 (57-69) | 63 (19-83) | |
| Disease entity | |||
| Nontransformed lymphoma (DLBCL, PMBCL) | 89 (82%) | 194 (78%) | .54 |
| Transformed lymphoma (trFL, trMCL, trMALT, trCLL, trHL) | 20 (18%) | 54 (22%) | |
| CAR-HEMATOTOX score ≥2 (HThigh) | 44 (40%) | 133 (54%) | .02 |
| LDH (median, IQR) | 236 (191-321) | 281.5 (260-318) | |
| CAR-T product | |||
| Axi-cel | 64 (59%) | 138 (56%) | .59 |
| Tisa-cel | 45 (41%) | 110 (44%) | |
| Prior autologous SCT | 34 (31%) | 68 (27%) | .48 |
| CRS (all-grade) | 94 (86%) | 209 (85%) | .63 |
| CRS (grade ≥3) | 5 (5%) | 24 (9%) | .10 |
| ICANS (all-grade) | 39 (36%) | 110 (39%) | .13 |
| ICANS (grade ≥3) | 12 (11%) | 39 (15%) | .24 |
| Tocilizumab use | 76 (70%) | 140 (56%) | .02 |
| Median cumulative tocilizumab during index admission, mg, (IQR) | 800 (0-1600) | NR | N/A |
| Corticosteroid use | 52 (48%) | 99 (40%) | .17 |
| Median cumulative steroid exposure during index admission, mg, (IQR of dexamethasone equivalency) | 0 (0-42) | NR | N/A |
| Prolonged corticosteroids (≥9 d) | 9 (8%) | 35 (14%) | .001 |
| ICAHT (day 0-30) | |||
| Grade 0-2 | 85 (78%) | Not available | N/A |
| Grade ≥3 | 24 (22%) | 70 (28%) | .16 |
| G-CSF | 29 (27%) | 106 (43%) | .004 |
| ICU admission | 17 (16%) | 37 (15%) | .87 |
| Infections events day 0-90 | 39 in 31 patients (28%) | 193 in 112 patients (45%) | .003 |
| Grade ≥3 infection events day 0-90 | 21 in 11 patients (11%) | 72 in 62 patients (25%) | .0013 |
| Microbiologically confirmed infections | 30 (77% of infection events) | 86 (45% of infection events) | N/A |
| Bacterial | 14 in 11 patients (11%) | 64 patients (26%) | .35§ |
| Bacterial (grade ≥3) | 8 in 5 patients (5%)† | 37 patients (15%)‡ | |
| Viral | 11 in 10 patients (8%) | 34 in 26 patients (10.5%) | |
| Fungal | 5 in 5 patients (5%) | 24 in 20 patients (8.2%) | |
| Clinically-defined infections | 9 in 9 patients (23%) | 107 events | .0002§ |
Axi-cel, axicabtagene ciloleucel; CL, chronic lymphocytic leukemia; DLBCL, diffuse large B-cell lymphoma; FL, follicular lymphoma; G-CSF, granulocyte colony-stimulating factor; HL, Hodgkin lymphoma; ICU, intensive care unit; MCL, mantle cell lymphoma; MALT, mucosal-associated lymphoid tissue; N/A, not applicable; NR, not reported; PMBCL, primary mediastinal B-cell lymphoma; SCT, stem cell transplantation; Tisa-cel, tisagenlecleucel.
P < .05 following χ² test of significance, categorical variables assessed with χ² test, and continuous variables assessed with Mann-Whitney U test.
Severe bacterial infections representing 32% of all infections, 42% of microbiologically confirmed infections and 7% of patients had a severe bacterial infection.
Number of severe bacterial infection by prophylaxis subgroup calculated from supplemental Figure 8 of Rejeski et al1, represents 13% of microbiologically confirmed infections, and 4% of all patients with an infection.
χ² calculated on the proportion of infection events reflected in each of the infection subtypes between studies.