Preventing Tumor Lysis Syndrome in Patients Receiving Venetoclax

What precautions should be taken to prevent tumor lysis syndrome (TLS) in patients receiving venetoclax (Venclexta)? —Name withheld on request

Venetoclax is an oral medication used to treat chronic lymphocytic leukemia (CLL). The drug inhibits the BCL2 protein, which results in apoptosis of the CLL cells. Due to its rapid effects, treatment management at initiation of venetoclax should include hydration, monitoring, and ramp-up dosing based on the patient’s risk for developing TLS.

Ramp-up dosing was used when high rates of TLS were seen in patients on a clinical trial after receiving venetoclax.¹ Use of ramp-up dosing and other strategies described below dramatically reduced the risk of TLS in subsequent patients.

The ramp-up titration is as follows. This can be adjusted on the basis of patient tolerance of therapy.

• 20 mg daily for the first week
• 50 mg daily for the second week
• 100 mg daily for the third week
• 200 mg daily for the fourth week
• 400 mg daily thereafter.

Risk stratification for TLS is based on tumor volume.

• Low risk All lymph nodes less than 5 cm in size and absolute lymphocyte count (ALC) less than 25 × 10⁹.
• Medium risk Any lymph node 5 to 10 cm or ALC 25 × 10⁹ or greater.
• High risk Any lymph node 10 cm or larger or any lymph node 5 cm or larger and ALC 25 × 10⁹ or greater.

All patients should receive hydration at each dose increase based on their TLS risk level. Patients at low risk should receive 1.5 to 2 L orally; patients at medium risk, at least 1.5 to 2 L orally, and may require additional IV hydration; patients at high risk, 1.5 to 2 L orally with additional IV hydration at 150 to 200 mL/hour as tolerated. 

All patients should be started on allopurinol 2 to 3 days prior to initiating venetoclax, and this should be continued until at least 3 to 7 days after the ramp-up titration has been completed. Rasburicase may be required in patients at high risk of TLS with elevated uric acid levels at baseline.

All patients receiving venetoclax require monitoring with each dose increase via laboratory tests, including potassium, uric acid, phosphorus, calcium and creatinine, conducted at the following intervals.

• Low risk Predose at each dose increase; 6 to 8 hours and 24 hours after the first 20 mg and 50 mg doses
• Medium risk If the patient has good renal function, use the same schedule as for low risk. Patients with impaired renal function (CrCl <80 mL/min) may require hospitalization and additional monitoring.
• High risk Patients should be hospitalized for the initial 20 mg and 50 mg doses. Laboratory monitoring should be conducted predose, 4 hours, 8 hours, 12 hours, and 24 hours after the initial 20 mg and 50 mg doses. If clinically appropriate, these patients may be managed as outpatients for subsequent increases and undergo monitoring predose, 6 to 8 hours, and 24 hours after doses.

If TLS occurs despite these measures, standard TLS management strategies (eg, increased hydration) should be employed and the next day’s venetoclax dose should be held. If TLS-associated laboratory changes resolve within 48 hours, continue at the current dose level. If TLS laboratory changes take more than 48 hours to resolve or if clinical symptoms are experienced, resume venetoclax at a reduced dose after TLS resolution.