Acute Kidney Injury after Chimeric Antigen Receptor T-Cell Therapy for Pediatric Acute Lymphoblastic Leukemia.

Background CD19-targeted chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable clinical efficacy in treating relapsed/refractory B-cell acute lymphoblastic leukemia (ALL). However, there are potential treatment-related toxicities, which may be severe. Acute kidney injury (AKI) has been reported after CD19 CAR T cells, but not systematically evaluated. We sought to describe AKI incidence, severity, outcome, and risk factors in the first 30 days after CTL019, a CD19 CAR T cell therapy, for ALL in pediatric patients. Methods We studied patients treated with CTL019 through two clinical trials (NCT01626495 and NCT02906371) at Children's Hospital of Philadelphia between April 2012 and April 2018. Demographic, laboratory and pharmacy data were automatically extracted from the electronic medical record using an EPIC data query tool. The primary outcome was AKI within 30 days after CTL019 infusion. AKI was defined using the Kidney Disease: Improving Global Outcomes criteria. Stage 1 (serum creatinine (SCr) >= 1.5 times the baseline) was classified as mild AKI. Stage 2 or 3 (SCr >=2 times the baseline) were classified as severe AKI. Renal recovery was defined as improvement in SCr to within 1.5 times the baseline by day +30. Log-binomial regression was used to estimate risk ratios for the association of cytokine release syndrome (CRS) and other patient characteristics with the development of AKI. Results A total of 125 patients and 3231 creatinine values were analyzed. Median patient age was 11.2 (range: 1.4-29.1) years at CTL019 infusion; 57.6% were male, 72% were Caucasian, and 82.4% were non-Hispanic. AKI developed in 26 patients (21.0%; 95% CI, 14.5 to 28.9), severe AKI developed in 15 patients (12%; 95% CI 7.3 to 19.1), and 3 patients (2.4%; 95% CI 0.7 to 7.3) required renal-replacement therapy. Among patients who developed AKI, 22 (88%: 95% CI 66.7 to 96.4) recovered renal function by day +30. Patients with Grade 3/4 CRS had a 4.9 times greater risk of developing AKI (95% CI, 2.4 to 9.9; p<.001) and a 10.3 times greater risk of developing severe AKI (95% CI 3.1 to 34.3; p<.001) than patients with no or Grade 1/2 CRS (Figure 1). The median time to CRS start, AKI onset, and maximum SCr level was 2, 7 and 9 days after infusion, respectively. History of hematopoietic cell transplant prior to CTL019 was not significantly associated with AKI, nor were age, sex, race, and ethnicity. Conclusion In the first 30 days after CTL019 infusion, 21% of patients developed AKI, but most recovered renal function by day +30. AKI was strongly associated with Grades 3 and 4 CRS and developed at a median of 5 days after the start of CRS. Additional analyses will compare the trajectories of CRS biomarkers and tumor lysis labs with the trajectory of AKI in order to better elucidate mechanisms of renal injury and identify opportunities for intervention. [ABSTRACT FROM AUTHOR]