Table 1.
Patient Characteristics and Laboratory Data
| All N=27 | carHLH and CRS N=4 | CRS alone N=11 | No CRS N=12 | P-Value | |
|---|---|---|---|---|---|
|
| |||||
| Age (Median; years) | 10.4(1.78–23.6) | 12.6(6.18–20.43) | 7.8(1.78–15.4) | 14.4(3.33–23.6) | 0.051 |
|
| |||||
| Sex N (%) | |||||
| Male | 15 (56.3) | 3 (75) | 5 (45,5) | 7 (58.3) | 0.67 |
| Female | 12 (43.8) | 1 (25) | 6 (54.5) | 5 (41.7) | |
|
| |||||
| Disease Burden^ N(%) | |||||
| PET-avidity | |||||
| Yes | 6 (22.3) | 3 (75) | 1 (9.1) | 2 (16.7) | 0.3 |
| No | 10 (37) | 1 (25) | 5 (45.5) | 4 (33.3) | |
| Not evaluated | 11 (40.7) | 0 (0) | 5 (45.5) | 6 (50) | |
| CNS Status | |||||
| CNS1 | 23 (87.5) | 0 | 11 (100) | 12 (100) | 0.0004* |
| CNS2/3 | 3 (9.4) | 3(75.0) | 0 (0) | 0 (0) | |
| Not evaluated | 1 (3.1) | 1 (25.0) | 0 (0) | 0 (0) | |
| Bone Marrow & | |||||
| <50% | 19 (70.4) | 1 (25) | 6 (54.5) | 12 (100) | 0.002* |
| ≥50% | 8 (29.6) | 3 (75) | 5 (45.5) | 0 | |
| Median (range) | 6.18 (0–100) | 71 (24.6–95.4) | 32.3 (0–100) | 0.92 (0–43.06) | 0.06 |
| Peripheral Blood # & | |||||
| <25% | 12 (44.4) | 0 (0) | 6 (54.5) | 6 (50) | 0.011* |
| ≥25% | 2 (7.4) | 2(50) | 0 (0) | 0 (0) | |
| Median (range) | 0.4 (0–56.2) | 43 (29.9–56.2) | 0.2 (0.05–2.7) | 0.4 (0–0.47) | 0.087 |
| Not evaluated | 13 (50) | 2 (50) | 5 (45.5) | 6 (50) | |
|
| |||||
| Infection** N(%) | |||||
| 14 days prior to infusion | |||||
| Yes | 4 (14.8) | 0 (0) | 2 (18.2) | 2 (16.7) | >0.999 |
| No | 23 (85.2) | 4 (100) | 9 (81.8) | 10 (83.3) | |
| 30 days after infusion | |||||
| Yes | 11(40.7) | 3 (75) | 5 (45.5) | 3 (25) | 0.255 |
| No | 16 (59.3) | 1(25) | 6 (54.5) | 9 (75) | |
| Active infection at CRS diagnosis | |||||
| Yes | 5 (33.3) | 1 (25) | 4 (36.4) | NA | >0.999 |
| No | 10 (66.7) | 3 (75) | 7 (63.6) | NA | |
|
| |||||
| CRS (Max Grade; N(%) | |||||
| 0 | 12 (44.4) | 0 (0) | 0 (0) | NA | 0.09 |
| 1 | 8 (29.6) | 1 (25) | 7 (63.6) | ||
| 2 | 2 (7.4) | 0 (0) | 2 (18.2) | ||
| 3 | 3 (11.1) | 1 (25) | 2 (18.2) | ||
| 4 | 2 (7.4) | 2 (50) | 0 (0) | ||
|
| |||||
| Disease Response N(%) | |||||
| CR | 19 (70.4) | 0 (0) | 10 (90.9) | 9 (75) | 0.018* |
| NR | 7 (25.9) | 3 (75) | 1 (9.1) | 3 (25) | |
| Not Evaluable | 1 (3.7) | 1 (25) | 0 (0) | 0 (0) | |
|
| |||||
| Survival %(CI) | |||||
| 1 month | 75 (12.8–96.1) | 100 | 100 | <0.0001* | |
| 2 months | 25 (0.89–66.5) | 90.9 (53.9–98.8) | 100 | ||
| 6 months | 0 | 91 (53.9–98.8) | 91.7 (63.2–99.1) | ||
| 12 months | 0 | 79.5 (36.1–94.4) | 92 (63.2–99.1) | ||
|
| |||||
| Laboratory Data [median value (range)] | |||||
|
| |||||
| Ferritin (ng/mL) | |||||
| Peak | 1711 (42– >100,000) | >100,000 (max) | 1767 (95–86211) | 1056 (42–6314) | 0.0032* |
| Change | 775 (0–98927) | 98,000 (95667–98927) | 1611 (73–84302) | 275 (0–3525) | 0.0015* |
|
| |||||
| CRP (mg/dL) | |||||
| Baseline | 0.5 (0.05–21.2) | 7.05 (6.1–21.2) | 1 (0.05–12.1) | 0.3 (0.05–1.9) | 0.0056* |
| Peak | 0.51(0.18–3.56) | 2.13(0.34–3.56) | 0.44(0.18–2.38) | 0.58(0.34–1.18) | 0.05 |
| Change | 0.22(0.09–2.97) | 1.82(0.18–2.97) | 0.18(0.09–2.08) | 0.24(0.11–0.4) | 0.035* |
|
| |||||
| Creatinine (mg/dL) | |||||
| Peak | 0.51(0.18–3.56) | 2.13(0.34–3.56) | 0.44(0.18–2.38) | 0.58(0.34–1.18) | 0.05 |
| Change | 0.22(0.09–2.97) | 1.82(0.18–2.97) | 0.18(0.09–2.08) | 0.24(0.11–0.4) | 0.035* |
|
| |||||
| ALT (U/L) | |||||
| Peak | 81(8–2128) | 934(77–2128) | 98(24–584) | 41(8–582) | 0.07 |
| Change | 70(2–2118) | 925(66–2118) | 82(17–572) | 28.5(2–566) | 0.06 |
|
| |||||
| Bilirubin (mg/dL) | |||||
| Peak | 0.7(0.15–8) | 3.35(1.3–8) | 0.6(0.15–1.2) | 0.55(0.2–2.5) | 0.011* |
| Change | 0.5(0–7.6) | 3.13(1–7.6) | 0.45(0–0.8) | 0.33(0.05–1.9) | 0.01* |
|
| |||||
| Fibrinogen (mg/dL) | |||||
| Minimum | 183(53–426) | 116(53–168) | 186(88–426) | 327(257–372) | 0.03* |
| Change | 64(0–506) | 298(64–506) | 67(0–291) | 0 | 0.02* |
| No data | 12 | 0 | 3 | 9 | |
|
| |||||
| INR | |||||
| Peak | 1.24(0.91–2.2) | 1.59(1.22–2.2) | 1.25(0.97–1.73) | 0.93(0.91–1.05) | 0.04* |
| Change | 0.2(0–0.74) | 0.45(0.11–0.74) | 0.21(0–0.54) | 0 (0–0.24) | 0.03* |
Cytokine Release Syndrome (CRS); CAR-mediated Hemophagocytic Lymphohistiocytosis (carHLH); Central Nervous System (CNS); Positron Emission Topography (PET); Minimal Residual Disease (MRD); Complete Response (CR; <5% blasts in bone marrow); No Response (NR; persistent disease post-CAR T-cell therapy at same magnitude as pre-CAR T-cell [MRD-positive pre/post or >5% blasts); C-reactive protein (CRP); Alanine Aminotransferase (ALT); International Normalized Ratio (INR); “Change” refers to the median change in minimum to peak level
statistically significant
unless otherwise noted: disease burden was assessed within 2-weeks of start of CAR T-cell therapy and after completion of any bridging therapy
Disease burden determined using flow-based technique for minimal residual disease (MRD) except for 2 patients without available MRD, and percent morphologic blasts was used for categorization
obtained on day of CAR T-cell infusion using MRD
Includes any viral, fungal or bacterial infections; Statistical significance between groups was compared using exact Chi-square test for categorical variables and the Kruskal-Wallis test for continuous variables. Missing data were excluded from the p-value.