Risk Assessment in Tumor Lysis Syndrome

Transcript:

Anthony R. Mato, MD, MSCE: Let’s discuss the risk factors for developing tumor lysis syndrome, or TLS. To begin, you want to think about the tumor type as a very important potential risk factor. Hematologic malignancies are at a higher risk than solid tumor malignancies, for example. Even within hematologic malignancies, you want to think about the more aggressive diseases, such as ALL [acute lymphoblastic leukemia], lymphoblastic lymphoma, diffuse large B-cell lymphoma, Burkitt lymphoma, and acute myelogenous leukemia.

TLS occurs when a tumor responds to a therapy. If you have TLS that’s treatment related, you want to have a therapy that’s active for patients. The more active and fast acting, the faster a therapy will debunk a tumor. Also, you have more risk for destroying cells and for the intracellular content to be spilled into the blood and cause the electrolyte and kidney disturbances that can be associated with TLS. The third thing you want to think about is the bulk of disease. A large cell lymphoma that’s low bulk might be quite different from a patient who has a very bulky disease.

By bulky disease, generally it’s the size of the lymph nodes, the size of the spleen, and how high the white blood cell count is related to the leukemia or the lymphoma. The more tumor, the bulkier the tumor, and the more risk there may be when those cells are killed to develop TLS.

The last thing is regarding the patient themselves—they comorbidities. Something to be considered, for example, is do they have kidney dysfunction? Do they have underlying cardiac disorders or arrhythmias? Those are smaller disturbances in things like uric acid or potassium that may lead to dysfunction, whereas in a younger, healthier patient who doesn’t have comorbidities, they may not have an arrhythmia. They may not have a neurological disturbance or kidney dysfunction. To sum it up, the risk factors include the tumor type—solid tumor vs. hematologic—and then the patient themselves and their underlying medical comorbidities.

How do I assess a patient’s risk of developing tumor lysis syndrome? There are several different models that are used to actually describe TLS when it occurs. One would be the Cairo-Bishop classification. There are also the Howard criteria. There are several. Those describe the TLS event, whether it’s a clinical event or a laboratory event.

The models are used for predicting whether tumor lysis syndrome would occur or not. In AML, or acute myelogenous leukemia, there are several models that are proposed. One that I was involved with had to do with the elevation of the white blood cell count, a patient’s LDH [lactate dehydrogenase], for example, and their renal dysfunction at baseline.

Predicting TLS is different from classifying TLS. Predicting largely has to do with tumor type, bulk of disease, as well as underlying organ dysfunction. When TLS occurs, you can use several models that are generally the same in terms of classifying the event as either a clinical event or a laboratory event. Laboratory means there is an abnormality in a number. The potassium and phosphate levels are elevated. The calcium is decreased, and the creatinine is elevated.

A clinical event means that that change in a number led to a clinical manifestation—arrhythmia, kidney dysfunction, the need for dialysis, perhaps a neurological event like a seizure, and so forth. There are different ways to predict the event and different ways to classify the event. That’s how I would break it down.

Thinking about which malignancies are leading to the higher risk of developing TLS, the breakdown would be solid tumor vs. hematologic malignancies. Hematologic malignancies by far are where there are classic episodes of TLS. If you want to open a textbook, the classic would be Burkitt lymphoma or ALL, which are the 2 that come to mind most frequently in the literature.

But there are also several other aggressive hematologic malignancies one would think about, including lymphoblastic lymphoma, both B-cell and T-cell type; certain types of mantle cell lymphoma; and leukemic B-cell lymphoma. You would rarely think about peripheral T-cell lymphoma, and then chronic lymphocytic leukemia would be the most common hematologic malignancies to lead to a TLS event.

Generally, responsiveness to therapy often predicts the ability to develop TLS. Whatever therapy you give first to a particular cancer is most likely to elicit the best response. In the setting of Burkitt lymphoma, ALL, or AML, this is generally an event for secondary to cytotoxic chemotherapy. This would include combinations of anthracycline-based chemotherapy—7+3 regimen—and some ALL regimens.

In chronic lymphocytic leukemia, this can be secondary to antibody-based therapy, like anti-CD20 antibodies. The drug that’s gotten the most attention more recently has been venetoclax, which is an anti-BCL2 medication or a BH3 mimetic, which has led to some TLS events.

Most events are actually minor. But they have the potential to have major complications in a small proportion of patients. The strategies to address TLS have to do with knowledge of the risk of the event, appropriate prophylaxis with IV [intravenous] fluids with monitoring of the heart rhythm, with uric acid—lowering agents, and then appropriate monitoring for the event.

What you need to think about is tumor type, prophylaxis, and then monitoring to mitigate the risk of a clinically significant event. That being said, there have been drugs developed over time largely focused at the uric acid portion of the equation, where the thought is that if you can metabolize, increase the solubility, or decrease uric acid, you may minimize the risk of renal complications—specifically uric acid crystallization or deposition in the renal tubules.

Drugs like allopurinol or febuxostat are aimed at decreasing the production of uric acid. Drugs like rasburicase, which is a brand name, or recombinant urate oxidase are aimed at metabolizing uric acid to a your insoluble form that can then be excreted from the kidney without that higher risk of crystallization or deposition in the tubule.

Transcript Edited for Clarity