Tumor lysis syndrome (TLS) has been shown to infrequently occur in treatment of chronic lymphocytic leukemia (CLL) using venetoclax with sufficient dose escalation. Recently, researchers analyzed real-world patterns of TLS and other outcomes with venetoclax for patients with CLL and reported their findings in Clinical Cancer Research.
In this multicenter, retrospective cohort analysis based on chart reviews, treatment patterns and outcomes were examined for 297 patients with CLL given venetoclax in clinical practice in the United States and the United Kingdom. Patients were grouped by baseline TLS risk.
Most patients (96%) had relapsed or refractory CLL. Chromosome 17p deletion was present in 45% of patients, 84% had unmutated IGHV, and 47% showed a creatinine clearance of less than 80 mL/min. TLS risk was considered high for 28% of patients, intermediate for 32%, and low for 40%. Most patients (80%) were treated with venetoclax monotherapy.
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Laboratory TLS was present in 5.7% of patients; 2.7% of patients experienced clinical TLS. Of the 25 instances of TLS observed, 10 occurred in patients in the high-risk category, 10 in intermediate-risk patients, and 5 in low-risk patients. TLS forced permanent discontinuation of venetoclax for 1 patient and was associated with 1 fatality following venetoclax reinitiation without dose escalation.
The researchers found that many patients were misclassified for TLS risk. Both higher TLS risk and low creatinine clearance were significantly associated with development of TLS.
TLS occurred among 14.7% of patients with a creatinine clearance below 80 mL/min and 5.0% of those with a higher creatinine clearance (P =.02).
The most common grade 3 or 4 adverse events reported were neutropenia (39.6%), thrombocytopenia (29.2%), and infection (25%). Toxicity was the reason for 19.3% of discontinuations.
Progression-free survival appeared unaffected by venetoclax dose reductions or interruptions.
The authors noted that TLS was more prevalent in this analysis than in clinical trials, but stated, “with improved attention to accurate risk classification and adherence to recommended TLS prophylaxis strategies, rates of TLS may be further reduced, likely translating to better patient outcomes.”
Disclosures: Some authors have declared affiliations with the pharmaceutical industry. Please refer to the original study for a full list of disclosures.
Reference
- Roeker LE, Fox CP, Eyre TA et al. Tumor lysis, adverse events, and dose adjustments in 297 venetoclax treated CLL in routine clinical practice [published online April 19, 2019]. Clin Cancer Res. doi:10.1158/1078-0432.CCR-19-0361
