Rates of adverse drug events and severity during 30 days after axi-cel infusion in RW patients compared with ZUMA-1
| AE and severity . | UC∗ (N = 416) . | ZUMA-1∗,† (N = 108) . | UC vs ZUMA-1¶ . | ||||
|---|---|---|---|---|---|---|---|
| Any grade (%) . | Grade 1/2 (%) . | Grade 3/4 (%) . | Any grade (%) . | Grade 1/2 (%) . | Grade 3/4 (%) . | P value . | |
| Hematological/organ function toxicity, n (%) | |||||||
| Any | 415 (99.8) | 396 (95.2) | 391 (94.0) | 108 (100.0) | 2 (1.9) | 97 (89.8) | .0801 |
| Hematological toxicity, n (%) | |||||||
| Anemia¶ | 85 (20.4) | 10 (2.4) | 75 (18.0) | 73 (67.6) | 24 (22.2) | 49 (45.4) | .00001 |
| Leukopenia | 94 (22.6) | 2 (0.5) | 92 (22.1) | 20 (18.5) | 2 (1.9) | 18 (16.7) | .2154 |
| Lymphopenia¶ | 2 (0.5) | 0 (0) | 2 (0.5) | 10 (9.3) | 2 (1.9) | 8 (7.4) | .00001 |
| Neutropenia | 223 (53.6) | 4 (1.0) | 219 (52.6) | 48 (44.4) | 6 (6.0) | 42 (38.9) | .0108 |
| Thrombocytopenia | 208 (50.0) | 55 (13.2) | 153 (36.8) | 38 (35.2) | 12 (11.1) | 26 (24.1) | .0131 |
| Organ function toxicity, n (%) | |||||||
| High AST | 109 (26.2) | 82 (19.7) | 27 (6.5) | 19 (17.6) | 12 (11.1) | 7 (6.5) | .9973 |
| High ALT | 144 (34.6) | 104 (25.0) | 31 (7.5) | 22 (20.4) | 16 (14.8) | 6 (5.6) | .4931 |
| Hypogammaglobulinemia | 263 (63.2) | 263 (63.2) | 0 (0) | 16 (14.8) | 16 (14.8) | 0 (0.0) | 1.0000 |
| Hyperbilirubinemia | 67 (16.1) | 66 (15.9) | 1 (0.2) | 5 (4.6) | 4 (3.7) | 1 (0.9) | .3033 |
| Electrolyte/metabolic toxicity, n (%) | |||||||
| Hypophosphatemia | 175 (42.1) | 52 (12.5) | 123 (29.6) | 31 (28.7) | 11 (10.2) | 20 (18.5) | .0216 |
| Hyponatremia | 235 (56.5) | 146 (35.1) | 89 (21.4) | 38 (35.2) | 26 (24.1) | 12 (11.1) | .0158 |
| Hypokalemia | 135 (32.5) | 94 (22.6) | 41 (9.9) | 36 (33.3) | 33 (30.6) | 3 (2.8) | .0181 |
| Hypocalcemia | 188 (45.2) | 152 (36.5) | 36 (8.7) | 43 (39.8) | 36 (33.3) | 7 (6.5) | .4636 |
| Hypoalbuminemia | 97 (23.3) | 87 (20.9) | 10 (2.4) | 43 (39.8) | 42 (38.9) | 1 (0.9) | .3398 |
| Hyperuricemia | 5 (1.2) | 0 (0) | 5 (1.2) | 2 (1.9) | 2 (1.9) | 0 (0.0) | .5887 |
| Immunological and neurological toxicity, n (%) | |||||||
| CRS | 380 (91.3) | 302 (72.6) | 78 (18.8) | 100 (92.6) | 88 (81.5) | 12 (11.1) | .0595 |
| Tocilizumab exposure‡ | 318 (76.4) | 259 (62.3) | 59 (14.2) | — | — | — | — |
| Anakinra exposure‡ | 41 (9.9) | 23 (5.5) | 18 (4.3) | — | — | — | — |
| Time to first tocilizumab, median (range), d | 3 (2-5) | 4 (2-5) | 2 (1-5) | — | — | — | — |
| ICANS | 312 (75.0) | 177 (42.5) | 135 (32.5) | 72 (66.7) | 37 (34.3) | 35 (32.4) | .9930 |
| Dexamethasone exposure§ | 264 (63.5) | 137 (32.9) | 127 (30.5) | — | — | — | — |
| Other glucocorticosteroid exposure§ | 96 (23.1) | 31 (7.5) | 65 (15.6) | — | — | — | — |
| Anakinra exposure§ | 41 (13.1) | 9 (5.1) | 32 (23.7) | — | — | — | — |
| Time to first dexamethasone (day), median (range) | 5 (3.75-6) | 5 (3-6) | 5 (4-6) | — | — | — | — |
| Other toxicity treatments and measures, n (%) | — | — | — | — | |||
| Filgrastim-sndz | 153 (36.8) | — | — | — | — | — | — |
| Immunoglobulin G | 41 (9.9) | — | — | — | — | — | — |
| Tumor lysis syndrome | 6 (1.4) | — | — | — | — | — | — |
| Infections¶ | 79 (19.0) | — | — | 8 (8) | — | — | .0039 |
| Hospitalization | |||||||
| Length of stay, median (range) | 12 (10-17) | — | — | — | — | — | — |
| Received transfusion | 90 (21.6) | ||||||
| Death¶ | 5 (1.2) | — | — | 9 (8) | — | — | .0001 |
| AE and severity . | UC∗ (N = 416) . | ZUMA-1∗,† (N = 108) . | UC vs ZUMA-1¶ . | ||||
|---|---|---|---|---|---|---|---|
| Any grade (%) . | Grade 1/2 (%) . | Grade 3/4 (%) . | Any grade (%) . | Grade 1/2 (%) . | Grade 3/4 (%) . | P value . | |
| Hematological/organ function toxicity, n (%) | |||||||
| Any | 415 (99.8) | 396 (95.2) | 391 (94.0) | 108 (100.0) | 2 (1.9) | 97 (89.8) | .0801 |
| Hematological toxicity, n (%) | |||||||
| Anemia¶ | 85 (20.4) | 10 (2.4) | 75 (18.0) | 73 (67.6) | 24 (22.2) | 49 (45.4) | .00001 |
| Leukopenia | 94 (22.6) | 2 (0.5) | 92 (22.1) | 20 (18.5) | 2 (1.9) | 18 (16.7) | .2154 |
| Lymphopenia¶ | 2 (0.5) | 0 (0) | 2 (0.5) | 10 (9.3) | 2 (1.9) | 8 (7.4) | .00001 |
| Neutropenia | 223 (53.6) | 4 (1.0) | 219 (52.6) | 48 (44.4) | 6 (6.0) | 42 (38.9) | .0108 |
| Thrombocytopenia | 208 (50.0) | 55 (13.2) | 153 (36.8) | 38 (35.2) | 12 (11.1) | 26 (24.1) | .0131 |
| Organ function toxicity, n (%) | |||||||
| High AST | 109 (26.2) | 82 (19.7) | 27 (6.5) | 19 (17.6) | 12 (11.1) | 7 (6.5) | .9973 |
| High ALT | 144 (34.6) | 104 (25.0) | 31 (7.5) | 22 (20.4) | 16 (14.8) | 6 (5.6) | .4931 |
| Hypogammaglobulinemia | 263 (63.2) | 263 (63.2) | 0 (0) | 16 (14.8) | 16 (14.8) | 0 (0.0) | 1.0000 |
| Hyperbilirubinemia | 67 (16.1) | 66 (15.9) | 1 (0.2) | 5 (4.6) | 4 (3.7) | 1 (0.9) | .3033 |
| Electrolyte/metabolic toxicity, n (%) | |||||||
| Hypophosphatemia | 175 (42.1) | 52 (12.5) | 123 (29.6) | 31 (28.7) | 11 (10.2) | 20 (18.5) | .0216 |
| Hyponatremia | 235 (56.5) | 146 (35.1) | 89 (21.4) | 38 (35.2) | 26 (24.1) | 12 (11.1) | .0158 |
| Hypokalemia | 135 (32.5) | 94 (22.6) | 41 (9.9) | 36 (33.3) | 33 (30.6) | 3 (2.8) | .0181 |
| Hypocalcemia | 188 (45.2) | 152 (36.5) | 36 (8.7) | 43 (39.8) | 36 (33.3) | 7 (6.5) | .4636 |
| Hypoalbuminemia | 97 (23.3) | 87 (20.9) | 10 (2.4) | 43 (39.8) | 42 (38.9) | 1 (0.9) | .3398 |
| Hyperuricemia | 5 (1.2) | 0 (0) | 5 (1.2) | 2 (1.9) | 2 (1.9) | 0 (0.0) | .5887 |
| Immunological and neurological toxicity, n (%) | |||||||
| CRS | 380 (91.3) | 302 (72.6) | 78 (18.8) | 100 (92.6) | 88 (81.5) | 12 (11.1) | .0595 |
| Tocilizumab exposure‡ | 318 (76.4) | 259 (62.3) | 59 (14.2) | — | — | — | — |
| Anakinra exposure‡ | 41 (9.9) | 23 (5.5) | 18 (4.3) | — | — | — | — |
| Time to first tocilizumab, median (range), d | 3 (2-5) | 4 (2-5) | 2 (1-5) | — | — | — | — |
| ICANS | 312 (75.0) | 177 (42.5) | 135 (32.5) | 72 (66.7) | 37 (34.3) | 35 (32.4) | .9930 |
| Dexamethasone exposure§ | 264 (63.5) | 137 (32.9) | 127 (30.5) | — | — | — | — |
| Other glucocorticosteroid exposure§ | 96 (23.1) | 31 (7.5) | 65 (15.6) | — | — | — | — |
| Anakinra exposure§ | 41 (13.1) | 9 (5.1) | 32 (23.7) | — | — | — | — |
| Time to first dexamethasone (day), median (range) | 5 (3.75-6) | 5 (3-6) | 5 (4-6) | — | — | — | — |
| Other toxicity treatments and measures, n (%) | — | — | — | — | |||
| Filgrastim-sndz | 153 (36.8) | — | — | — | — | — | — |
| Immunoglobulin G | 41 (9.9) | — | — | — | — | — | — |
| Tumor lysis syndrome | 6 (1.4) | — | — | — | — | — | — |
| Infections¶ | 79 (19.0) | — | — | 8 (8) | — | — | .0039 |
| Hospitalization | |||||||
| Length of stay, median (range) | 12 (10-17) | — | — | — | — | — | — |
| Received transfusion | 90 (21.6) | ||||||
| Death¶ | 5 (1.2) | — | — | 9 (8) | — | — | .0001 |
ALT, alanine aminotransferase; AST, aspartate aminotransferase.
Em dash (−) indicates values not applicable or not assessed for that column or cohort.
All values in ZUMA-1 were extracted from the associated publications with a total of 108 trial participants. The missing values in ZUMA-1 columns were not reported.
Unadjusted P values of Fisher exact tests comparing rates of severe (grade ≥3) AE observed in UC and ZUMA-1 for all AEs except hypogammaglobulinemia for which total rates were compared.
Of 416 patients, 380 experienced CRS. The percentages for the exposures of tocilizumab and anakinra were calculated based on these 380 patients.
Of 416 patients, 342 experienced ICANS. The percentages for the exposures to dexamethasone, other glucocorticoids, and anakinra were calculated based on these 342 patients.
Severe AEs with rates observed in UC and ZUMA-1 remained significantly different after correction for multiple-hypothesis testing using the Bonferroni method.