Renal Effects and Recovery in Patients Receiving Chimeric Antigen Receptor T Cell Therapy

Abstract

Introduction Chimeric Antigen Receptor T cell (CAR T) therapy has shown significant therapeutic potential but carries risk of treatment related toxicity. There is limited data describing risk of acute kidney injury (AKI) related to CAR T therapy. Objectives To identify the incidence of AKI and recovery of renal function in patients undergoing CAR T therapy. Methods We analyzed adult patients given FDA approved CAR T cell therapy February 2018 to 2019 for Non-Hodgkin Lymphoma (NHL) at our center. Patients received axicabtagene ciloleucel (Yescarta®) (34/46, 74%) or tisagenlecleucel (Kymriah®) (12/46, 26%). All creatinine's prior to and following CAR T infusion until last follow up were collected. Maximum (max) grade AKI [grade 1 (creatinine 1.5 - 3-fold baseline)] was calculated based on KDIGO criteria. Renal recovery was assessed using creatinine 30 days post max grade AKI. Results Forty six patients, median age 63 years (range 19-85) of whom 33 (72%) were men underwent CAR T therapy for relapsed/ refractory NHL. Patients had a median of 4 lines of chemotherapy (range 2-10) prior to CAR T, including autoSCT (n=9, 20%), alloHCT (n=3, 7%), and both auto and alloHCT (n=1). Lymphodepletion regimens were either cyclophosphamide/fludarabine (n=43, 93%) or bendamustine (n=3, 7%). Baseline co-morbidities were hypertension 13/46 (28%) and diabetes mellitus 1/46 (2%). Median baseline creatinine was 0.8 (range 0.5 – 2) mg/dL, and median glomerular filtration rate (GFR) was 88 [(range 36-160) mL/min/1.73m2, GFR ≤ 60 in 4 patients]. No patient was on dialysis prior to infusion. Five of 14 patients with baseline urinalysis had ≥30 mg/dL protein. Median overall follow up was 8.3 (95%CI: 6.8 - 11.4) months. Renal injury Fourteen patients (30%) had any grade AKI during available follow-up. Of these, 10/14 (71%) had grade 1, 2/14 (14%) had grade 2, and 1/14 (7%) had grade 3. Median day onset for max grade AKI was 48 (range 6 to 100) days. Nephrotoxic medication exposures prior to AKI included acyclovir in 10 (71%), vancomycin in 11 (79%) and ibuprofen in 1 (7%). Of the 14 patients who developed AKI, 11 (79%) also had cytokine release syndrome (CRS). For these patients, median peak C reactive protein level was 12 (range 0.4 to 34) mg/L and median interleukin-6 level was 179 (range 14 to 23,752) pg/ml. After removing competing events (relapse, progression or death), cumulative incidence of grade 1 AKI was 15.2% (95% CI 4.7-25.7) and grade 2 AKI was 2.2% (95% CI 0-6.5) by day +100. Incidence of AKI shown in Figure 1. Creatinine returned to baseline in 11/12 (92%) patients alive at 30 days post AKI. Conclusions Our study shows that the incidence of AKI is low in patients receiving CAR T therapy. Majority of AKI was grade 1 and returned to baseline within 30 days. A larger study sample will likely help elucidate risk factors associated with development of AKI in these patients.