Venetoclax is a potent targeted therapy for the treatment of chronic lymphocytic leukemia (CLL), which acts by inhibiting the B‐cell lymphoma‐2 (BCL2) protein. While venetoclax has revolutionized the treatment of CLL, tumor lysis syndrome remains a significant risk with its use. Tumor lysis syndrome (TLS) is a cluster of metabolic abnormalities that result from rapid tumor destruction. Venetoclax kills cancer cells so effectively and quickly that the body doesn’t have time to clear out all the debris released from the cancer cells breaking open. This rapid uncontrolled release of intracellular contents, such as electrolytes and uric acid, can cause cardiovascular dysfunction, renal dysfunction, and neurological dysfunction.
At the International Workshop on CLL (iwCLL) 2019, our own Dr. Brian Koffman interviewed Dr. Anthony Mato, Director of the CLL Program at Memorial Sloan Kettering Cancer Center. They discussed recent research on risk factors that may help predict which patients develop tumor lysis syndrome.
Takeaways:
- The current TLS risk stratification model is based on information from the manufacturer’s drug label and the FDA.
- Patients are categorized as low, medium, or high risk based primarily on lymphocyte count and lymph node size. Based on the risk level, healthcare professionals can make decisions on whether the patient needs to receive treatment as an outpatient procedure or in the hospital, how much fluid they need, and if they need any other agents to minimize risk.
- However, in the clinical practice, doctors have seen some patients who are categorized as low or medium risk and still go on to develop electrolyte abnormalities
- Researchers were interested in whether there were other factors that could help with predicting the likelihood of developing TLS.
- They performed modeling with data from 339 patients from academic and community practice sites. The risk factor that stood out the most was creatinine clearance, which is a measure of kidney function.
- Researchers chose a cutoff of creatinine clearance = 80 ml/min. The current venetoclax drug label states that patients with reduced creatinine clearance (<80 ml/min) are at increased risk of TLS.
- Creatine clearance appeared to be a risk factor independent of the recommended risk stratification.
- Creatinine clearance is regularly measured in healthcare settings and the information should be readily available to use in clinical decision making.
- Creatinine clearance shouldn’t necessarily influence whether to start venetoclax, but it should inform how venetoclax is administered (ie, in an office or hospital, amount of fluids needed, etc.).
Conclusions:
While venetoclax is a very effective therapy for CLL, clinicians need to assess each patient’s risk for TLS prior to initiating treatment. In addition to those standard assessments of lymphocyte count and lymph node size, new research provides support for the use of creatine clearance as an independent risk factor when assessing risk level. This information can help clinicians make important decisions about how venetoclax should be administered in their practices.
Please enjoy this interview with Dr. Mato from September 2019 at iwCLL in Edinburgh, Scotland.
Take care of yourself first.
Ann Liu, PhD
