Venetoclax produces durable effects in relapsed/refractory CLL
EXPERT ANALYSIS AT THE NCCN ANNUAL CONFERENCE
Mitigating tumor lysis syndrome risk
General measures for mitigating the risk of tumor lysis syndrome include identification of patients at increased risk, initiation of prophylaxis with hydration and a uric acid reducing agent, and initiation of venetoclax at a 20 mg dose for 1 week, with gradual step-wise ramp-up over 5 weeks to the target dose, Dr. Zelenetz noted.
As reported by Stilgenbauer, et al., patients with a nodal mass less than 5 cm and absolute lymphocyte count (ALC) of 25,000 or less are considered at low risk for tumor lysis syndrome, those with a nodal mass of 5 cm to less than 10 cm or ALC greater than 25,000 are at medium risk, and those with a nodal mass of 10 cm or greater or nodal mass of 5 cm or greater and ALC of greater than 25,000 are considered to be at high risk.
High-risk patients in the study received inpatient venetoclax dosing and monitoring at 4, 8, 12, and 24 hours with 20 mg and 50 mg dosing, as well as outpatient intravenous hydration at 100 mg if there was no indication to hospitalize, and post-dose 8-24 hour laboratory monitoring at 100 mg and above.
Medium-risk patients received IV hydration at 20 and 50 mg dosing, inpatient care if creatinine clearance was less than 80 mL/min or if there was a high tumor burden, and postdose 8- and 24-hour laboratory monitoring after the initial dose and at dose escalations. Low-risk patients received outpatient dosing at all dose levels in the absence of an indication to hospitalize, and postdose 8- and 24-hour laboratory monitoring after the initial dose and at dose increases.
“Unfortunately, the dose-limiting toxicity of venetoclax is fatal tumor lysis,” Dr. Zelenetz said, adding that by increasing the dose slowly over time according to current treatment recommendations – from 20 mg, to 50, 100, 200, and 400 mg at weekly intervals, this complication can be avoided.
Dr. Zelenetz reported receiving consulting fees, honoraria, and/or grant/research support from Genentech, the maker of venetoclax (Venclexta), and a wide variety of other drug companies.
