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Antihyperuricemic Therapy in TLS

Insights From: Michael R. Bishop, MD, University of Chicago; Anthony R. Mato, MD, MSCE, Memorial Sloan Kettering Cancer Center
Published: Friday, May 15, 2020



Transcript:

Michael R. Bishop, MD: Agents that lower hyperuricemia play an extremely important role in TLS [tumor lysis syndrome].  The use of these agents is dependent upon the identification of the patient’s risk of developing TLS. There are some patients who you consider at low risk for TLS, and that includes individuals who have a lot of solid tumors with low tumor bulk where perhaps you don’t need an agent to prevent or lower hyperuricemia. It’s in the intermediate- and high-risk patients where the role and the 2 major agents of this would be allopurinol and rasburicase.

In patients who are at extreme high risk or already have established hyperuricemia, that’s where you’re going to use rasburicase. In those intermediate-risk patients, that’s where it becomes more difficult to choose what specific agent you may select. You're going to feel quite comfortable with just hydration and allopurinol. In the high-intermediate group, you’re going to be thinking more of rasburicase as a preventive measure in trying to help those patients.

What is the risk of a patient with developing TLS in the setting of a normal uric acid level? That’s actually a more complicated question than you think because there are relative normal uric acid levels. A large amount of studies have actually looked at this. For a patient who has a low normal—generally, we would put this at a value of 0 mg/dL to 4 mg/dL—the incidence of TLS with those levels of uric acid is actually very low, less than 5%. For mostly normal values that you see at any hospital between 4 mg/dL and 8 mg/dL, the incidence of TLS in a patient, would be somewhere between 25% to 30%. When you get over a level of the incidence of TLS, it is greater than 75%.

Various factors put patients at risk for TLS. Again, this is a disease that is highly sensitive chemotherapy and is known to have a high degree of activity against that disease. A good example of that would be the use of the monoclonal antibody rituximab in the setting of lymphoma. This would be for patients with large tumor bulk and patients who come in with pre-existing diseases, particularly renal insufficiency or some degree of renal failure. Then, there is an entity known as spontaneous tumor lysis where the patients will already present with either laboratory or clinical manifestations of TLS before they can receive therapy. It’s because their tumor is proliferating and breaking down so rapidly that they already have TLS at presentation.

Anthony R. Mato, MD, MSCE: For most of the tumor types that I have mentioned, a standard measure will be to provide allopurinol, for example, to all patients. It does not work if you’re starting it on the day of therapy, and so it’s good to plan ahead. If you’re planning to give somebody therapy 48 hours or 72 hours from now, start the allopurinol as early as possible. The earlier you start, the more efficacious it will be in preventing uric acid production.
             
In terms of managing hyperuricemia, there is not a tremendous role in the acute setting for using uric acid lowering agents, like allopurinol or febuxostat. You should also think about recombinant urate oxidase or rasburicase, where that drug can lower uric acid from quite elevated levels to normal or below-normal levels within several hours.

Transcript Edited for Clarity
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Transcript:

Michael R. Bishop, MD: Agents that lower hyperuricemia play an extremely important role in TLS [tumor lysis syndrome].  The use of these agents is dependent upon the identification of the patient’s risk of developing TLS. There are some patients who you consider at low risk for TLS, and that includes individuals who have a lot of solid tumors with low tumor bulk where perhaps you don’t need an agent to prevent or lower hyperuricemia. It’s in the intermediate- and high-risk patients where the role and the 2 major agents of this would be allopurinol and rasburicase.

In patients who are at extreme high risk or already have established hyperuricemia, that’s where you’re going to use rasburicase. In those intermediate-risk patients, that’s where it becomes more difficult to choose what specific agent you may select. You're going to feel quite comfortable with just hydration and allopurinol. In the high-intermediate group, you’re going to be thinking more of rasburicase as a preventive measure in trying to help those patients.

What is the risk of a patient with developing TLS in the setting of a normal uric acid level? That’s actually a more complicated question than you think because there are relative normal uric acid levels. A large amount of studies have actually looked at this. For a patient who has a low normal—generally, we would put this at a value of 0 mg/dL to 4 mg/dL—the incidence of TLS with those levels of uric acid is actually very low, less than 5%. For mostly normal values that you see at any hospital between 4 mg/dL and 8 mg/dL, the incidence of TLS in a patient, would be somewhere between 25% to 30%. When you get over a level of the incidence of TLS, it is greater than 75%.

Various factors put patients at risk for TLS. Again, this is a disease that is highly sensitive chemotherapy and is known to have a high degree of activity against that disease. A good example of that would be the use of the monoclonal antibody rituximab in the setting of lymphoma. This would be for patients with large tumor bulk and patients who come in with pre-existing diseases, particularly renal insufficiency or some degree of renal failure. Then, there is an entity known as spontaneous tumor lysis where the patients will already present with either laboratory or clinical manifestations of TLS before they can receive therapy. It’s because their tumor is proliferating and breaking down so rapidly that they already have TLS at presentation.

Anthony R. Mato, MD, MSCE: For most of the tumor types that I have mentioned, a standard measure will be to provide allopurinol, for example, to all patients. It does not work if you’re starting it on the day of therapy, and so it’s good to plan ahead. If you’re planning to give somebody therapy 48 hours or 72 hours from now, start the allopurinol as early as possible. The earlier you start, the more efficacious it will be in preventing uric acid production.
             
In terms of managing hyperuricemia, there is not a tremendous role in the acute setting for using uric acid lowering agents, like allopurinol or febuxostat. You should also think about recombinant urate oxidase or rasburicase, where that drug can lower uric acid from quite elevated levels to normal or below-normal levels within several hours.

Transcript Edited for Clarity
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