Tumor Lysis Syndrome in Venetoclax-Treated CLL in Clinical Trial, Real-World Patients

Venetoclax (Ven) has helped patients with chronic lymphocytic leukemia (CLL) achieve improved long-term outcomes with well-tolerated fixed-duration regimens; however, Ven also comes with the risk of tumor lysis syndrome (TLS) because of its pro-apoptotic impact on CLL cells. If left unmanaged, laboratory TLS can turn into clinical TLS and cause renal insufficiency, cardiac arrhythmias, seizures, and death. Strategies for mitigating Ven TLS include TLS risk assessment, five-week dose ramp-up, prophylaxis with hydration and oral uric acid reducers, and closely monitoring blood chemistry depending on risk levels. TLS risk may also be reduced before Ven therapy with debulking techniques. A study assessing rates of TLS and outcomes in CLL in the clinical trial and post-marketing settings was presented at the 62nd ASH Annual Meeting & Exposition.

Eight studies were queried to collect trial data on 1,138 patients treated with current TLS mitigation measures (treatment naïve, n=304; relapsed/refractory [R/R], n=834). Post-marketing data were collected from AbbVie Global Safety Database (GSD; n=236) and five publications of real-world usage (n=817).

In the pooled clinical studies data, the incidence of TLS adverse events (AEs) was 1.8% (n=20), of which 15 were laboratory TLS AEs and five were clinical TLS AEs. In all cases, TLS was transient, and patients returned to therapy with no permanent sequelae. No deaths from TLS were recorded.

Per commercial tracking, between 2016 and 2019, an estimated 20,000 patients with CLL started Ven outside of clinical trials. A total of 236 reports of TLS were identified in the GSD; 17 had severe consequences—all in R/R patients—that were deemed caused by TLS, including 13 that were fatal and four necessitating dialysis. The median age of these patients was 69 years, and they had multiple comorbidities. More than half of these patients (n=10; 59%) were hospitalized before initiating Ven. Where data were available, it was found that TLS presented in patients with high (n=3), medium (n=6), and low (n=1) TLS risk. TLS was most likely to present after a Ven 20 mg dose (n=8) but was also witnessed in six cases after a Ven 100 mg dose and once each after Ven 50 mg and 400 mg doses.

There were five real-world studies on TLS incidence, and they largely focused on patients with R/R CLL. In these studies, TLS incidence was anywhere from 6% to 13%.

“For clinical TLS in the post-marketing setting, it is important for healthcare professionals to follow recommended preventive measures, particularly applying appropriate risk assessment, prophylaxis and dose ramp-up, blood chemistry monitoring and early intervention, and dose modifications for drug interactions,” the researchers concluded.