Incidence of Laboratory Tumor Lysis Syndrome in CAR T-Cell Recipients

• Published in: Transplantation and cellular therapy Vol. 30; no. 2; p. S451
• Main Authors: Sicre, David, Shah, Shreya A, Shalhoub, Sila D, Piedra, Katrina M, Spiegel, Jay
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 01-02-2024
• ISSN: 2666-6367; 2666-6367
• DOI: 10.1016/j.jtct.2023.12.653

Tumor lysis syndrome (TLS) is a complication commonly seen in hematological malignancies after patients receive antineoplastics due to the rapid release of cell contents including potassium, phosphorus, and the breakdown of nucleic acids to produce high levels of uric acid. Despite landmark chimeric antigen receptor (CAR) T-cell trials reporting TLS to be an uncommon adverse event, there is a lack of consensus on utilizing prophylactic allopurinol as a preventative strategy. Currently, there are no randomized trials that have assessed TLS as a primary endpoint with CAR T-cell recipients. At our institution, allopurinol is provided to all recipients 24-48 hours in advance of lymphodepletion (LD) and continued for a few days after the CAR T-cell infusion.
Determine the incidence of TLS in CAR T-cell recipients in order to assess if prophylaxis is warranted.
This was a single center, retrospective review performed in adult CAR T-cell recipients from January 2021 to March 2023 that received either axicabtagene ciloleucel or brexucabtagene autoleucel. TLS was defined as at least two metabolic abnormalities within 3 days before or 7 days after initiation of chemotherapy including uric acid level ≥ 8 mg/dL, potassium level ≥ 6.0 mEq/L, phosphate level ≥ 4.5 mg/dL or any change greater than 25% from baseline, plus acute kidney injury (AKI) characterized by an increase in serum creatinine (SCr) levels ≥ 1.5x the upper limit of normal (ULN). Descriptive statistics were used.
Out of the 77 patients included the incidence of metabolic abnormalities greater than the ULN in uric acid, potassium, and phosphorus was 3%, 1%, and 14%, respectively. For clinical manifestations of TLS, median baseline (day -5) SCr levels were 0.89 mg/dL with only two patients meeting criteria for stage 1 AKI and one patient for stage 3 AKI. The TLS incidence overall was 3% (2 patients). One patient met criteria with lab abnormalities on day -1 including uric acid, phosphorus, and SCr peaking at 7.4 mg/dL, 7.4 mmol/L, and 1.71 mg/dL, respectively, which is possible TLS. The other patient met criteria late on day +7 with lab abnormalities including uric acid, phosphorus, and SCr peaking at 3.6 mg/dL, 5.3 mmol/L, and 1.15 mg/dL, respectively, which was likely not related to TLS.
Out of the two patients with protocol defined TLS, only one had possible TLS with stage 3 AKI, a SCr peak at 1.7 mg/dL from a baseline of 0.5 mg/dL, with extensive disease (mediastinal mass >10 cm) and a complicated course. A risk-stratified approach may be warranted to identify high risk patients with certain characteristics (i.e., bulky tumor with progressive disease) who would benefit from prophylactic allopurinol for TLS prevention.