Table 2.
Clinical features of CAR T-cell–mediated hematotoxicity
| Disease entity | Clinical features | Pooled (n = 235) |
Training cohort (n = 55) | European validation cohort (n = 80) |
P | United States validation cohort (n = 100) |
P | Tisa-cel (n = 76) |
Axi-cel (n = 159) |
P |
|---|---|---|---|---|---|---|---|---|---|---|
| Severe thrombocytopenia | Platelet count <50 g/L | 145 (62) | 40 (73) | 52 (65) | .32 | 53 (53) | .02 | 42 (57) | 103 (64) | .31 |
| Anemia | Hemoglobin <8 g/dL or requiring transfusion | 162 (69) | 43 (78) | 54 (68) | .15 | 65 (65) | .10 | 46 (62) | 116 (72) | .13 |
| Neutropenia | ||||||||||
| Severe | ANC ≤500 cells per µL | 213 (91) | 54 (98) | 69 (86) | .009 | 90 (90) | .10 | 60 (81) | 153 (95) | .001 |
| Profound | ANC ≤100 cells per µL | 169 (72) | 47 (85) | 54 (68) | .03 | 68 (68) | .02 | 40 (54) | 129 (80) | <.001 |
| Protracted, severe | ANC ≤500 cells per µL for ≥7 days | 160 (68) | 42 (76) | 51 (64) | .11 | 67 (67) | .27 | 41 (55) | 119 (74) | .007 |
| Protracted, profound | ANC ≤100 cells per µL for ≥7 days | 60 (26) | 16 (29) | 25 (31) | .99 | 19 (19) | .16 | 11 (15) | 49 (30) | .01 |
| Prolonged | ANC ≤1000 cells per µL measured ≥21 days after CAR T-cell transfusion | 151 (64) | 43 (78) | 58 (73) | .52 | 50 (50) | <.001 | 42 (57) | 109 (68) | .11 |
| Primary end point: duration of severe neutropenia from day 0 to day 60 (95% CI) | 9 (8-10) | 12 (10-15) | 10.5 (8-14) | .14 | 8 (7-9) | <.001 | 9.5 (6-12) | 9 (8-10) | .27 | |
| Binary end point: severe neutropenia ≥14 days | 67 (29) | 22 (40) | 33 (41) | .99 | 12 (12) | <.001 | 22 (28) | 46 (29) | .99 |
The training cohort was compared with both the European and US validation cohorts. Grade 4 neutropenia, ANC <500 cells per µL; grade 3 to 4 anemia, hemoglobin <8 g/dL; grade 3 to 4 thrombocytopenia, platelet count <50 g/L. Statistical significance (P < .05) between groups was determined by Fisher’s exact two-sided t test for incidence rates and Mann-Whitney U test for the primary end point.