Table 1.
Main characteristics of studies included in this meta-analysis of AKI incidence and mortality among patients treated with CAR-T cell therapy
| Study | Year | Age | Indications for CAR-T therapy | Total number of patients (n) | AKI definition | AKI incidence/ severe AKI | Cause of AKI/biopsy | CRS grading | Baseline GFR | CRS with AKI vs. CRS without AKI | Mortality |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Sauter et al.S2 | 2014 | 61 yr (34−68 yr) | DLBCL B-NHL |
6 | Not defined | Overall AKI, 1/6 = 16.6% | NA | Non-severe CRS, 1/2 = 50% Severe (grade 4 CRS), 1/2 = 50% |
NA | Overall CRS, 2/6 = 33.3% No AKI mortality defined |
NA No AKI mortality defined |
| Lee et al.S3 | 2014 | 5−27 yr (range) | Refectory B-ALL, NHL | 21 | Not defined | Overall AKI, 1/21 = 5% | NA | CRS grade 1, 8/16 = 50% CRS grade 2, 2/16 = 12.5% CRS grade 3, 3/16 = 18.75% CRS grade 4, 3/16 = 18.75% |
NA | Overall CRS, 16/21 = 76%, No AKI CRS defined |
NA |
| Kochenderfer et al.S4 | 2015 | 49 yr (range 30−68 yr) | DLBCL, CLL, B CELL lymphoma |
15 | Not defined | Overall AKI, 1/15 = 7% | NA | NA | NA | NA | Overall, 30- day mortality, 1/15 = 7% No AKI mortality defined |
| Ali et al.S5 | 2016 | 50 yr (range not reported) | MM | 12 | Not defined | Overall AKI, 2/12 = 16.6% | NA | CRS grade 3 and 4, 2/4 = 50% | NA | Overall CRS, 4/12 = 33.3% | NA |
| Fitzgerald et al.S1 | 2017 | Median 11 yr (range 5−22 yr) | B-ALL | 39 | KDIGO | Overall AKI, 18/39 = 46% Stage 1, 9/39 = 23% Stage 2, 6/39 = 15% Stage 3, 3/39 = 8% None required RRT |
NA | CRS grade 1, 2/36 = 6% Grade 2, 16/36 = 44.4% Grade 3, 7/36 = 19.4% Grade 4, 11/36 = 30.5% |
NA | Overall CRS, 36/39 = 92% | NA |
| Locke et al.S6 | 2017 | 49 yr (range 29−68 yr) | DLBCL | 7 | Needing RRT | AKI needing RRT, 1/7 = 14% | NA | CRS grade 1 and 2, 5/6 = 83% CRS grade 3, 0 CRS grade 4, 1/6 = 17% |
NA | Overall CRS, 6/7 = 86% AKI with CRS, 1/6 = 16% |
9-mo Overall mortality, 4/7=57% No AKI mortality defined |
| Hay et al.S7 | 2017 | 54 y (median 20−73 yr) | ALL CLL NHL |
133 | Not defined | Overall AKI, 3/133 = 2.25% (AKI reported in only grade 4 CRS patients) AKI needing RRT, 1/133 = 0.75% |
NA | CRS grade 1−3,83/93 = 89.3% CRS grade 4−5, 10/93 = 10.7%. |
NA | Overall CRS, 93/133 = 70% AKI with CRS, 3/93 = 3% |
NA |
| Maude et al.S8 | 2018 | 11 yr (3−23 yr) | B- ALL | 75 | Needing RRT | AKI needing RRT, 7/75 = 9% | NA | CRS grade 1 and 2, 23/58 = 40% CRS grade 3, 16/58 = 28% CRS grade 4, 19/58 = 32% |
NA | Overall CRS, 58/75 = 77% AKI with CRS needing RRT, 7/58 = 12% |
Overall 12- mo mortality, 19/75 = 25% |
| Rives et al.S9 | 2018 | Two groups: 1) <18 yr) (median = 10 yr, range 3−17 yr) 2) 18−25 yr (median 20 yr, range 18−25 y) |
B- ALL | <18 yr, n = 84 18−25yr, n = 20 |
Needing RRT Needing RRT |
NA NA |
NA NA |
CRS > grade 3, = 44% CRS >/ grade 3, 45% |
NA | Overall CRS, 66/84 = 79% AKI/RRT with CRS, 7/66 = 11% Overall CRS, 18/20 = 90% AKI/RRT with CRS, 4/18 = 22% |
Overall mortality >30 days, 21/84 = 25% Overall mortality, >30 days 8/20 = 40% |
| Hartsell et al.S10 | 2019 | <25 yr (no range mentioned) | ALL DLDCL AML |
40 | Not defined | Overall AKI, 7/40 = 17.5% | NA | NA | NA | NA | Overall mortality in-hospital, =3/40 = 7.5% |
| Hartsell et al.S11 | 2019 | >18 yr (no range mentioned) | B Cell Lymphoma, MM, Follicular lymphoma, ALL |
735 | Not defined | Overall AKI, 110/735 = 15% |
NA | NA | NA | NA | Overall-in hospital mortality, 30/735 = 4% |
| TalleurS12 | 2019 | <21 yr (no range mentioned) | Refractory ALL | 5 | Grade 3 AKI | Grade 3 AKI, 1/5 = 20% | NA | Grade 1 CRS, 1/1 = 100%. No mention of other grades |
NA | Overall CRS, 1/5 = 20% CRS with AKI, 1/1 = 100% |
NA |
| Myers et al.S13 | 2019 | 11 yr (range 1.4−29.1 yr) | Refractory B ALL | 125 | KDIGO | Overall AKI, = 26/125 (21.0%; 95% CI = 14.5−28.9), Severe AKI (KDIGO stage 2 and 3) 15 patients (12%; 95% CI = 7.3− 19.1), 3 patients (2.4%; 95% CI = 0.7−7.3) required RRT. |
Patients with CRS had a 4.9 times greater risk of developing AKI (95% CI = 2.4− 9.9; P < 0.001) and a 10.3 times greater risk of developing severe AKI (95% CI = 3.1− 4.3; P < 0.001) | NA | NA | Overall CRS, 100/125 = 80% |
NA |
| Metwally et al.S14 | 2019 | Adults (age not defined) | DLBCL | N = 58 | Rise in creatinine >0.3 above baseline | Overall AKI, 19/58 = 33% | NA | NA | NA | NA | AKI mortality at 6 months, 47% compared to 13% in non-AKI patients (P = 0.008) |
| Myers et al.S15 | 2019 | 12 yr (range 1.4− 29.1 yr) | ALL | Total N = 213, ICU admission, n = 49 |
Needing RRT | AKI needing RRT among ICU-admitted patients, 4/213 = 1.9% | NA | NA | NA | NA | Overall 30-day mortality, 2/213 = 1% |
| Harris et al.S16 | 2020 | >18 yr | DLBCL | 1570 | Not defined | Overall AKI, 247/1570 = 15.7% | NA | NA | NA | NA | Overall mortality, 30/1570 = 1.5% (in-hospital mortality) No AKI mortality reported |
| Hiramatsu et al.S17 | 2020 | Range 5−24 yr |
B-ALL | 6 | Needing RRT | AKI needing RRT, 2/6 = 33% | NA | CRS grade 3, 2/5 = 40% CRS grade 4, 3/5 = 60% |
NA | Overall CRS, 5/6 = 83% AKI with CRS, 2/5 = 40% |
Overall 12-mo mortality, 2/6 = 33% No AKI mortality defined |
| Gutgarts et al.S18 | 2020 | 63 yr (range 19−86 yr) | DLBCL, NHL |
46 | KDIGO | Overall AKI, 14/46 = 30% (95% CI = 16.9%− 43.9%) Grade 1 AKI, 10/46 = 22% (95% CI = 9.7%− 33.8%) Grade 2, 2/46 = 4.5% Grade 3, 1/46 = 2.17% Grade 2/3 AKI, 8% (95% CI = 4%− 17%) incidence of grade 2−3 AKI No patients needed RRT |
CRS, 11/14 = 79% | CRS grade 1 and 2, 31/37 = 84% CRS grade 3 and 4, 6/37 = 16% |
Median GFR, 88 ml/min per 1.73 m2 (range, 36−160 ml/min per 1.73 m2) | Overall CRS, 37/46 = 80% (95% CI = 66% to 90.5%) CRS with AKI, 10/14 = 79% |
30-day AKI mortality, 2/14 = 14% |
| Gupta et al.S19 | 2020 | 60 yr (mean age 60 ± 13 yr) |
DLBCL | 78 | KDIGO | Overall AKI, 15/78 = 19% Stage 1, 7/78 = 9% Stage 2, 2/78 = 3% Stage 3, 6/78 = 6% AKI requiring RRT, 3/78 = 4% |
Decreased kidney perfusion, 8 = 8/15 = 53% (CRS = 7/8) ATN, 6 = 6/15 = 40% (CRS = 6/6) Post- obstruction, 11/15 = 7% |
CRS Grade 0, 12/66 = 18%. CRS grade 1, 28/66 = 42.4% CRS grade 2, 28/66 = 42.4% CRS grade 3, 8/66 = 12% CRS grade 4, 2/66 = 3% |
109+/17 ml/min per 1.73 m2 | Overall CRS, 66/78 = 85% CRS with AKI, 13/15 = 86% |
Overall 6-mo mortality, 11/78 = 14% 6-mo AKI mortality, 5/15= 33% |
| Qu et al.S20 | 2020 | 48 yr (range 41−58 yr) | DLBCL | 10 (C-CAR-T, n = 4) (R- CAR-T, n = 6) |
Not defined | Overall AKI, 3/10 = 30 % | NA | CRS grade 3−5 (C-CAR-T), 4/10 = 40% CRS grade 1−2 (R-CAR-T), 6/10 = 60% |
NA | Overall CRS, 10/10 = 100% | NA |
| ValadeS21 | 2020 | 56 yr (median (27−65 yr) | DLBCL ALL |
41 | AKI needing RRT | Overall AKI, 2/41 = 5% | NA | NA | NA | Overall CRS, 39/41 = 95% | NA |
| Lee et al.S22 | 2020 | Mean age 60 yr (SD 18 yr) | DLBCL | 37 | AKI ≥1.5-fold rise in sCr from baseline |
Overall AKI, 2/37 = 5% Stage 3 AKI, 2/37 = 5% AKI requiring RRT, 0/37 = 0% |
NA | CRS grade 1, 15/20 = 75%. Grade 2, 4/20 = 20% Grade 3 and 4, 0 Grade 5, 1/20 = 5% |
Baseline creatinine = 0.54 mg/dl | Overall CRS, 20/37 = 54% | Overall mortality, 5/37 = 14% AKI mortality,= 2/37 = 5% |
AKI, acute kidney injury; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; B-NHL, B-cell non-Hodgkin’s lymphoma; CLL, chronic lymphoblastic leukemia; CRS, cytokine release syndrome; DLBCL, diffuse large B-cell lymphoma; GFR, glomerular filtration rate; ICU, intensive care unit; KDIGO, Kidney Disease: Improving Global Outcomes; NA, not available; NHL, non-Hodgkin's lymphoma; MM, multiple myeloma; RRT, renal replacement therapy; sCr, serum creatinine.