Systematic Review Determines the Incidence of Tumor Lysis Syndrome With Tyrosine Kinase Inhibitors in Hematologic Malignancies

Tumor lysis syndrome (TLS) consists of a group of metabolic abnormalities that may occur spontaneously in patients with a hematologic malignancy or as a result of cytotoxic therapy in patients with cancer. The syndrome results from the rapid release of cytokines, electrolytes, and nucleic acids that occurs with the destruction of malignant cells. The movement of electrolytes from the inside to the outside of cells then overwhelms normal homeostatic mechanisms and results in hyperkalemia, hyperphosphatemia, hyperuricemia, and hypercalcemia. 

As a result, untreated TLS can cause life-threatening arrhythmias, acute kidney injury, and neurologic complications. Treatment of TLS requires correction of electrolyte imbalances, fluid resuscitation, renal replacement therapy, careful monitoring, and the use of uric-acid–lowering agents such as allopurinol and rasburicase. 

Because TLS has a mortality rate as high as 79% during induction therapy in patients with some malignancies, the syndrome constitutes a medical emergency. Moreover, the risk of TLS is greatest in patients who are being treated for hematologic malignancies rather than solid tumors. Some studies have indicated that the syndrome affects as many as 40% of adult patients with hematologic malignancies. 

“Unfortunately, the true incidence of TLS is unknown,” wrote Brittany Salter, MD, PhD, McMaster University, Hamilton, Ontario, Canada, and colleagues, adding, “The key to TLS prevention is to identify intermediate-to-high risk patients and apply appropriate prophylaxis and monitoring”. Dr Salter and colleagues continued, “However, the management of hematologic malignancy has evolved rapidly, and there has been the advent of many novel targeted therapies; it is not known if these agents contribute to TLS, and as such these agents are yet to be incorporated into the TLS risk stratification process.”

To determine the incidence of TLS during the treatment of hematologic malignancy with one such class of therapies, the tyrosine kinase inhibitors (TKIs), Dr Salter and team conducted a systematic review of the medical literature by searching the EMBASE, MEDLINE, and Web of Science electronic databases (Eur J Haematol. 2022; doi:10.1111/ejh.13786). They supplemented this search by doing a manual search of the American Society of Hematology and American Society of Clinical Oncology abstract databases. Keywords searched included: tumor lysis syndrome, tyrosine kinase inhibitors, lymphoma, and leukemia.

Using these methods, the researchers identified 57 publications that mentioned the incidence of TLS when TKIs were used to treat hematologic malignancy and found that 39 of those publications reported TLS as an adverse event. Moreover, “TLS was described as an adverse event among essentially all the sub-classes of TKIs that are used to manage hematologic malignancies,” Dr Salter and team noted.

“The overall number of articles commenting on TLS as an adverse event is sparse, and there needs to be more transparency regarding the incidence of TLS when employing newer targeted therapies,” they concluded, adding, “Physicians should consider the risk of TLS on an individual basis and the added risk of TLS when using TKIs to treat hematologic malignancy.”