Baseline characteristics of patients with CRS + HLH-LTs, HG-CRS without HLH-LTs, and NLG-CRS without HLH toxicities
| . | CRS + HLH-LT, n = 26 . | HG-CRS without HLH-LT, n = 17 . | NLG-CRS without HLH-LT, n = 141 . | P value . |
|---|---|---|---|---|
| Age, median (IQR), y | 11.5 (4.5-16.75), n = 26 | 13 (10-18), n = 17 | 12 (8-18), n = 141 | .45 |
| Male, n (%) | 13/26 (50.0) | 10/17 (58.8) | 87/141 (61.6) | .53 |
| Race/ethnicity, n (%) | ||||
| Hispanic | 10/26 (38.5) | 7/17 (41.2) | 53/141 (37.6) | .93 |
| Non-Hispanic White | 14/26 (53.8) | 8/17 (47.1) | 67/141 (47.5) | |
| Other | 2/26 (7.7) | 2/17 (11.8) | 21/141 (14.9) | |
| Initial cytogenetic risk category, n (%) | ||||
| Favorable | 2/18 (11.1) | 3/13 (23.1) | 19/108 (17.6) | .55 |
| Intermediate | 7/18 (38.9) | 2/13 (15.4) | 40/108 (37.0) | |
| Unfavorable | 9/18 (50.0) | 8/13 (61.5) | 49/108 (45.4) | |
| Risk stratification at end of induction, n (%) | ||||
| Low risk | 0/23 (0.0) | 0/16 (0.0) | 6/116 (5.2) | .09 |
| Standard risk | 0/23 (0.0) | 1/16 (6.3) | 20/116 (17.2) | |
| High risk | 8/23 (34.8) | 5/16 (31.3) | 19/116 (16.4) | |
| Very high risk | 15/23 (65.2) | 10/16 (62.5) | 71/116 (61.2) | |
| Timing of initial B-ALL relapse, n (%) | ||||
| On therapy relapse | 17/26 (65.4) | 6/17 (35.3) | 39/142 (27.5) | .0008∗∗∗ |
| Early relapse | 8/26 (30.8) | 6/17 (35.3) | 32/142 (22.5) | .39 |
| Late relapse | 5/26 (19.2) | 5/17 (29.4) | 44/142 (30.9) | .48 |
| Lines of therapy before CAR, median (IQR) | 2 (1.25-4), n = 26 | 2 (1-3), n = 17 | 2 (1-3), n = 141 | .35 |
| Prior CD19-directed therapy, n (%) | 8/26 (30.8) | 4/17 (23.5) | 25/141 (17.7) | .28 |
| Optimal† lymphodepleting chemotherapy, n (%) | 11/20 (55) | 8/15 (53.3) | 82/116 (70.7) | .18 |
| BM disease burden %, median (IQR) | 66.0 (26.2-84.0), n = 25 | 8.0 (3.7-36.0), n = 13 | 5.0 (0.24-28.7), n = 80 | <.0001∗∗∗∗ |
| B-ALL disease burden, n (%) | ||||
| Low | 0 (0.0) | 6 (37.5) | 76 (55.1) | <.0001∗∗∗∗ |
| High∗ | 26 (100.0) | 10 (62.5) | 62 (44.9) | |
| Total (n) | 26 | 16 | 138 | |
| Timing of pre–CAR T-cell infusion BM assessment, median (IQR), wk | 2.5 (1.0-9.0), n = 26 | 2.0 (1.25-4.63), n = 16 | 2.0 (1.1-7.8), n = 138 | .87 |
| Peripheral blasts, % of white blood cells, median (IQR) | 25 (0-50), n = 22 | 0 (0-0), n = 15 | 0 (0-0), n = 127 | <.0001∗∗∗∗ |
| CNS disease pre–CAR T-cell infusion (CNS 2 + 3), n (%) | 2/19 (10.5) | 0/12 (0.0) | 10/118 (8.5) | .63 |
| Extramedullary disease pre–CAR T-cell infusion, n (%) | 3/26 (11.5) | 2/17 (11.8) | 10/141 (7.1) | .50 |
| Pre–CAR T-cell infusion ALC (cells per μL), median (IQR) | 30 (0.1-60), n = 21 | 50 (17.5-97.5), n = 16 | 70 (20-157.5), n = 134 | .09 |
| Pre–CAR T-cell infusion ANC (cells per μL), median (IQR) | 10 (0-160), n = 21 | 490 (197.5-1175), n = 16 | 530 (232.5-1040), n = 134 | <.0001∗∗∗∗ |
| Pre–CAR T-cell infusion platelet (×109/L), median (IQR) | 35.5 (20.25-92), n = 26 | 110.0 (46-148), n = 17 | 121.5 (56-206), n = 138 | <.0001∗∗∗∗ |
| Pre–CAR T-cell infusion ferritin (ng/mL), median (IQR) | 3745 (1291.8-6194.6), n = 25 | 831 (663.0-2174.5), n = 15 | 1364 (603.5-2660.4), n = 115 | .002∗∗ |
| Pre–CAR T-cell infusion CRP (mg/dL), median (IQR) | 3.165 (1.01-7.29), n = 22 | 0.559 (0.390-2.30), n = 14 | 0.600 (0.300-2.51), n = 111 | .006∗∗ |
| CAR viability (%), median (IQR) | 88.6 (87.6-93.3), n = 25 | 87.0 (85.3-95.5), n = 17 | 87.6 (83.2-92.2), n = 140 | .13 |
| CAR dose infused (CAR T cells × 106/kg), median (IQR) | 1.585 (1.23-2.48), n = 26 | 1.630 (1.28-2.00), n = 16 | 1.80 (1.33-2.45), n = 139 | .60 |
| Transduction efficiency (no. of copies per cell), median (IQR) | 0.315 (0.26-0.40), n = 24 | 0.400 (0.27-0.55), n = 16 | 0.34 (0.21-0.51), n = 130 | .32 |
| CAR expression by flow (% CAR+ viable cells), median (IQR) | 14.50 (10.50-18.80), n = 25 | 14.10 (12.20-16.30), n = 17 | 14.05 (9.80-19.10), n = 136 | .97 |
| . | CRS + HLH-LT, n = 26 . | HG-CRS without HLH-LT, n = 17 . | NLG-CRS without HLH-LT, n = 141 . | P value . |
|---|---|---|---|---|
| Age, median (IQR), y | 11.5 (4.5-16.75), n = 26 | 13 (10-18), n = 17 | 12 (8-18), n = 141 | .45 |
| Male, n (%) | 13/26 (50.0) | 10/17 (58.8) | 87/141 (61.6) | .53 |
| Race/ethnicity, n (%) | ||||
| Hispanic | 10/26 (38.5) | 7/17 (41.2) | 53/141 (37.6) | .93 |
| Non-Hispanic White | 14/26 (53.8) | 8/17 (47.1) | 67/141 (47.5) | |
| Other | 2/26 (7.7) | 2/17 (11.8) | 21/141 (14.9) | |
| Initial cytogenetic risk category, n (%) | ||||
| Favorable | 2/18 (11.1) | 3/13 (23.1) | 19/108 (17.6) | .55 |
| Intermediate | 7/18 (38.9) | 2/13 (15.4) | 40/108 (37.0) | |
| Unfavorable | 9/18 (50.0) | 8/13 (61.5) | 49/108 (45.4) | |
| Risk stratification at end of induction, n (%) | ||||
| Low risk | 0/23 (0.0) | 0/16 (0.0) | 6/116 (5.2) | .09 |
| Standard risk | 0/23 (0.0) | 1/16 (6.3) | 20/116 (17.2) | |
| High risk | 8/23 (34.8) | 5/16 (31.3) | 19/116 (16.4) | |
| Very high risk | 15/23 (65.2) | 10/16 (62.5) | 71/116 (61.2) | |
| Timing of initial B-ALL relapse, n (%) | ||||
| On therapy relapse | 17/26 (65.4) | 6/17 (35.3) | 39/142 (27.5) | .0008∗∗∗ |
| Early relapse | 8/26 (30.8) | 6/17 (35.3) | 32/142 (22.5) | .39 |
| Late relapse | 5/26 (19.2) | 5/17 (29.4) | 44/142 (30.9) | .48 |
| Lines of therapy before CAR, median (IQR) | 2 (1.25-4), n = 26 | 2 (1-3), n = 17 | 2 (1-3), n = 141 | .35 |
| Prior CD19-directed therapy, n (%) | 8/26 (30.8) | 4/17 (23.5) | 25/141 (17.7) | .28 |
| Optimal† lymphodepleting chemotherapy, n (%) | 11/20 (55) | 8/15 (53.3) | 82/116 (70.7) | .18 |
| BM disease burden %, median (IQR) | 66.0 (26.2-84.0), n = 25 | 8.0 (3.7-36.0), n = 13 | 5.0 (0.24-28.7), n = 80 | <.0001∗∗∗∗ |
| B-ALL disease burden, n (%) | ||||
| Low | 0 (0.0) | 6 (37.5) | 76 (55.1) | <.0001∗∗∗∗ |
| High∗ | 26 (100.0) | 10 (62.5) | 62 (44.9) | |
| Total (n) | 26 | 16 | 138 | |
| Timing of pre–CAR T-cell infusion BM assessment, median (IQR), wk | 2.5 (1.0-9.0), n = 26 | 2.0 (1.25-4.63), n = 16 | 2.0 (1.1-7.8), n = 138 | .87 |
| Peripheral blasts, % of white blood cells, median (IQR) | 25 (0-50), n = 22 | 0 (0-0), n = 15 | 0 (0-0), n = 127 | <.0001∗∗∗∗ |
| CNS disease pre–CAR T-cell infusion (CNS 2 + 3), n (%) | 2/19 (10.5) | 0/12 (0.0) | 10/118 (8.5) | .63 |
| Extramedullary disease pre–CAR T-cell infusion, n (%) | 3/26 (11.5) | 2/17 (11.8) | 10/141 (7.1) | .50 |
| Pre–CAR T-cell infusion ALC (cells per μL), median (IQR) | 30 (0.1-60), n = 21 | 50 (17.5-97.5), n = 16 | 70 (20-157.5), n = 134 | .09 |
| Pre–CAR T-cell infusion ANC (cells per μL), median (IQR) | 10 (0-160), n = 21 | 490 (197.5-1175), n = 16 | 530 (232.5-1040), n = 134 | <.0001∗∗∗∗ |
| Pre–CAR T-cell infusion platelet (×109/L), median (IQR) | 35.5 (20.25-92), n = 26 | 110.0 (46-148), n = 17 | 121.5 (56-206), n = 138 | <.0001∗∗∗∗ |
| Pre–CAR T-cell infusion ferritin (ng/mL), median (IQR) | 3745 (1291.8-6194.6), n = 25 | 831 (663.0-2174.5), n = 15 | 1364 (603.5-2660.4), n = 115 | .002∗∗ |
| Pre–CAR T-cell infusion CRP (mg/dL), median (IQR) | 3.165 (1.01-7.29), n = 22 | 0.559 (0.390-2.30), n = 14 | 0.600 (0.300-2.51), n = 111 | .006∗∗ |
| CAR viability (%), median (IQR) | 88.6 (87.6-93.3), n = 25 | 87.0 (85.3-95.5), n = 17 | 87.6 (83.2-92.2), n = 140 | .13 |
| CAR dose infused (CAR T cells × 106/kg), median (IQR) | 1.585 (1.23-2.48), n = 26 | 1.630 (1.28-2.00), n = 16 | 1.80 (1.33-2.45), n = 139 | .60 |
| Transduction efficiency (no. of copies per cell), median (IQR) | 0.315 (0.26-0.40), n = 24 | 0.400 (0.27-0.55), n = 16 | 0.34 (0.21-0.51), n = 130 | .32 |
| CAR expression by flow (% CAR+ viable cells), median (IQR) | 14.50 (10.50-18.80), n = 25 | 14.10 (12.20-16.30), n = 17 | 14.05 (9.80-19.10), n = 136 | .97 |
CNS, central nervous system; IQR, interquartile range.
∗High BM disease burden is defined as ≥5% lymphoblasts, the presence of peripheral blasts, and/or extramedullary disease.
Optimal lymphodepleting chemotherapy: fludarabine area under the curve of ≥13.8 mg × hr/L using a pharmacokinetic model. CNS indicates central nervous system; IQR, 25th to 75th percentile interquartile range; lactate dehydrogenase. P values: Kruskal-Wallis tests for comparison of continuous variables and Fisher exact tests for comparison of categorical variables with a 2-tailed significance level of .05.