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Acute kidney injury (AKI) occurs in 30% of patients infused with chimeric antigen receptor (CAR) T-cells. The purpose of this study was to identify risk factors and long-term outcomes after AKI in patients who received CAR T-cell therapy.
Medical records of 115 adult patients with R/R hematological malignancies treated with CD19-targeted CAR T-cells at Vall d'Hebron University Hospital between July 2018 and May 2021 were reviewed. Laboratory parameters including serum creatinine and blood hemoglobin were reviewed and values were gathered for days +1, +7, +14, +21, and +28 post-infusion.
A total of 24/115 patients developed AKI related to CAR T-cell therapy (Table 1); 6/24 with AKI over chronic kidney disease (CKD). Two patients had AKI in the context of lymphodepleting chemotherapy and the other 22 after CAR T-cell infusion, starting at day+1 in 3 patients, day+7 in 13 patients, day +14 in 1 patient, day+21 in 2 patients, and day+28 in 3 patients. Renal function was recovered in 79% patients within the first month after infusion. Male gender, CKD, cytokine release syndrome (CRS), and immune effector cell-associated neurotoxicity syndrome (ICANS) were associated with AKI. Male gender, CKD, ICANS grade≥3 and CRS grade ≥2 were identified as independent risk factors for AKI on multivariable analysis (Table 2). The most frequent CAR T-cell related complications, CRS developed in 95 (82%) patients and ICANS in 33 (29%). Steroids were required in 34 (30%) patients and tocilizumab in 37 (32%). Six (5%) patients were admitted to the intensive care unit (1 septic shock, 4 CRS grade ≥2 associated to ICANS grade ≥2, and 1 CRS grade ≥3). A total of 5/36 patients died in the first 30 days after CAR T-cell infusion for reasons other than disease progression, including 4 cases of infectious complications and 1 of heart failure.
The peak cumulative incidence in the full patient population of hyponatremia reached 15%, hypophosphatemia in 22% and hypocalcemia in 43% by day +7, hypopotassemia in 21% and hypomagnesemia in 74% by day +21. In comparison between the AKI and non-AKI groups, hypophosphatemia and hypocalcemia by day +1 (p=0.002 and p=0.01, respectively), hyponatremia and hypocalcemia by day + 7 (p=0.001 and p=0.03, respectively), hypocalcemia by day + 14 (p=0.03), and hyponatremia by day + 21 (p=0.04) showed significant differences in the univariable analysis. However, these differences were not seen in the adjusted multivariable analysis.
At a median follow-up of 296 days, the mean progression-free survival (PFS) was 198 days [95% CI, 100 to 297 days] in AKI patients vs 161 days [95% CI, 115 to 208 days] in non-AKI patients (p=0.72). The mean overall survival (OS) was 281 days [95% CI, 27 to 227 days] in AKI patients versus 300 days [95% CI, 278 to 323 days] in non-AKI patients (p=0.77). The median PFS was 41 days [95% CI, 25 to 57 days] in CKD patients vs 132 days [95% CI, 81 to 182 days] in normal kidney function patients (p=0.94). The OS was 305 days [95% CI, 230 to 380 days] in CKD patients versus 295 days [95% CI, 273 to 317 days] in normal kidney function patients (p=0.33).
Our results suggest that AKI is a frequent but mild adverse event, with fast recovery after CART-cell therapy infusion.