TLS is characterized by the abrupt release of cellular components into the bloodstream following the lysis of malignant cells. There are different classification systems, including the Cairo-Bishop and Howard criteria. TLS has more recently been associated with venetoclax use, and different therapies may be linked to varying risk of TLS, owing to tumor sensitivity to different mechanisms of action. TLS may occur with any anti-CLL regimen, but whenever you are using agents such as venetoclax, rituximab, obinutuzumab, or fludarabine, there is a significant risk of TLS.

The monitoring and treatment of TLS is clinically challenging and depends on the patient’s risk assessment. This individual level of risk dictates how frequently labs are performed, where the monitoring takes place, and what constitutes appropriate prophylaxis. Risk for TLS is influenced by a number of variables, including tumor burden, taking into consideration both white blood cell count and tumor bulk by lymphadenopathy. Impaired renal function at baseline also increases the risk.

Low- and intermediate-risk patients can generally be monitored in the outpatient setting, but intermediate-risk patients may be monitored and may receive intravenous fluids in the inpatient setting in some circumstances. High-risk patients are always monitored for at least the first 2 doses of venetoclax therapy in the inpatient setting. Uric acid–lowering agents such as allopurinol may be used, and intravenous fluids, particularly for intermediate- and high-risk patients, are given to reduce the risk of TLS and to provide appropriate intravascular volume for renal perfusion; recombinant urate oxidase is used in some cases to help clear uric acid from the blood and to avoid precipitation in the renal tubules. With venetoclax, there is no dose adjustment for those at risk for TLS, and all patients receive the same 5-week ramp-up. The labeling for venetoclax is particular for how TLS monitoring and prophylaxis should occur; there are no shortcuts, and the label must be followed. When these guidelines are adhered to, there may be a low rate of laboratory TLS, but the risk of serious complications is very low. Laboratory TLS consists of electrolyte abnormalities that might presage clinical TLS but are not, themselves, clinically significant or associated with manifestations of clinical TLS (eg, cardiac arrhythmia, death, seizure, acute renal injury with serum creatinine >1.5 times the upper limit of normal). We provide patients with reassurance that, when this guidance is followed, they have a low risk of TLS, as evidenced by the very low reports of these events in the more recent clinical trials, specifically with venetoclax.