Tumor Lysis Syndrome: Unmet Needs and Future Directions in Care


Closing out their discussion on tumor lysis syndrome management, James Short, MD, and John Reagan, MD, highlight unmet needs and future evolutions in the treatment landscape.


John L. Reagan, MD: This is where we are in terms of treatment. One is initial recognition of who’s at risk. Two would be doing prophylaxis for patients who are intermediate or high risk for tumor lysis syndrome [TLS]. Where do you see the field going? What are the future directions for patients with cancer? [Comment on] prophylaxis for them against tumor lysis identification of who’s at risk or treating tumor lysis syndrome. Where do you see that headed?

Nicholas James Short, MD: It’s hard to say. There’s a lot of room for more data because this is a data-free landscape. You covered almost all the publications and abstracts on this topic. We don’t have a lot of data about the right strategy. We have limited data that help guide a lot of our clinical decision-making in terms of what uric acid level might be appropriate to give rasburicase. But we don’t have much. A lot of the recommendations for managing tumor lysis syndrome, or preventing it, are guided by expert opinion or clinical algorithms based largely on expert opinion.

What information might be helpful to have to make this less of an issue or concern for our patients? If we had good biomarkers, that could help. A lot of times, if you see a lot of patients with hematologic malignancies, you get much better at identifying if this is real TLS, is this a patient that’s high risk. Of course, there are some guidelines to help you risk stratify, but a lot of it comes with clinical experience.

Sometimes patients have hyperuricemia from their chronic renal dysfunction, and some have hyperuricemia that’s causing renal dysfunction, and that hyperuricemia is from TLS. When you have similar laboratory studies between 1 group and the other, how do we distinguish what’s TLS and what’s not? A biomarker could help us distinguish [when to] think that this is tumor lysis syndrome vs this is just hyperuricemia that’s not going to have any clinical consequence. That could be helpful.

In many ways, LDH [lactate dehydrogenase] is helpful for that. It’s not perfect, but an LDH gives you a marker of cell turnover. If that’s very high, then this looks like a patient who’s more likely to be high risk or to experience TLS as opposed to baseline renal dysfunction with some hyperuricemia. LDH is very imperfect, but a biomarker like it that was a little more specific for TLS, or at least for the underlying pathology, would certainly be helpful.

When we’re thinking about the future of monitoring and preventing TLS, there’s a link between the type of therapies that we have and the tumor type. Both of those impact the risk of TLS. If you don’t have any effective therapies for a particular malignancy, then you’re not going to see treatment-induced TLS. You might see spontaneous TLS, but you’re not going to see treatment induced.

As we get new therapies, depending on what the mechanism of actions are for those, theoretically we can get TLS across a wider number of entities. I treat hematologic malignancies only, but I’m sure many solid tumor doctors would be happy if they heard that there was some new drug for pancreatic cancer that caused tumor lysis syndrome, because that [would be] a sign that it’s working. Ultimately, we have to think about this as we develop these new drugs. Every time we’re developing a new drug in a clinical trial, we have to be aware of the underlying mechanism of action. In those clinical trials, we often add a lot of TLS monitoring because sometimes with a new drug, we don’t know if it’s going to increase the risk of TLS. For example, in the development of venetoclax, it was initially surprising that it was causing rapid tumor lysis syndrome. I’m sure there could be other drugs in the future developed for all different types of malignancies where the same thing can happen.

Ultimately, better preventive strategies will be helpful. It’s difficult to give adequate hydration to all patients. We try to, along with [giving] diuretics. But if patients have bad underlying cardiomyopathy or other cardiac issues, that can be challenging. Even though we have good antihyperuricemic drugs, such as allopurinol and rasburicase, this isn’t enough to prevent all the complications of tumor lysis syndrome. This doesn’t address the hyperkalemia, which can lead to arrhythmias. It doesn’t necessarily address the calcium phosphate deposition that can lead to renal dysfunction independent of the uric acid levels.

There are many ways we can get more information about the appropriate prevention for patients, better treatments, and better biomarkers. As we develop new drugs, we have to be cognizant that [the patients] who might be high risk for TLS might change, and it may be linked to the therapies we have.

We’ve covered a lot. Do you have any final words? Is there something in particular you want people to take away from all this?

John L. Reagan, MD: There have been many changes in terms of how we do things. It’s true with the assessment: what’s the diagnosis, what are the features of that patient, do they have baseline renal dysfunction, do they have gout? We know we can have hyperuricemia with gout, and that could be why the uric acid is high. Is there an alternative explanation for 1 of these lab values being [abnormal]? In CLL [chronic lymphocytic leukemia], is it because all the cells died off in the tube, and that’s why the potassium level is through the roof? That’s spurious hyperkalemia.

[We have] the diagnosis and the patient specifics, and then it’s imperative which treatment you’re going to give. For a lot of our patients, that’s why they’re admitted to the hospital, because they’re not sure [what’s going on]. They’re in for monitoring to make sure there’s no TLS, no CRS [cytokine release syndrome], or other things that can happen. It’s important to screen these things out and acknowledge them, and to acknowledge that things change over time. The patient condition will change over time.

In the recent Howard modification of the Cairo-Bishop [criteria], it’s important when you see creatinine [increase] a little, if someone has a baseline creatinine of 0.6 mg/dL and the next day it’s 0.9 mg/dL, then that’s something we should probably look at. Try to make sure patients are getting adequately hydrated, they’re on allopurinol, [and on] all the things that they need to be. Use that full-team approach: pharmacists, PAs [physician assistants], NPs [nurse practitioners]. Everyone is recognizing these things. Even internal medicine doctors might [see a patient] coming in with an auto tumor lysis. All of that’s so important in terms of that team approach of making sure we’re able to get them over the hump of this initial presentation.

Nicholas James Short, MD: We covered a lot, John. It was a great discussion. Thank you for joining me. I’m glad we could do it together, and I hope the audience found it helpful.

Transcript edited for clarity.

Related Videos
Jorge J. Castillo, MD,
Video 4 - "Challenges in Adopting Targeted Therapies for BRAF Alterations"
Video 3 - "BRAF V600E Mutant Ganglioglioma"
Catherine C. Coombs, MD, associate clinical professor, medicine, University of California, Irvine School of Medicine
Michael Leung, PharmD, an expert on colorectal cancer
A panel of 4 experts on colorectal cancer
Video 4 - "The Evolving Treatment Landscape with CDK4/6 Inhibitors in Early HR+/HER2- Breast Cancer"
Richard Finn, MD, and David James Pinato, MD, MRCP, PhD, experts on hepatocellular carcinoma
Richard Finn, MD, and David James Pinato, MD, MRCP, PhD, experts on hepatocellular carcinoma
Alessandra Ferrajoli, MD