Accreditation/Credit Designation

Physicians’ Education Resource®, LLC, is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.

Physicians’ Education Resource®, LLC, designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from Sanofi Genzyme.

Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis Syndrome


Release Date: June 30, 2018
Expiration Date: June 30, 2019
Media: Internet - based
 

Activity Overview

This activity, Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis Syndrome, developed in Physicians’ Education Resource, LLC, (PER®) established Oncology Briefings™ legacy format, is an online interactive monograph that provides an overview of recent data regarding the management of tumor lysis syndrome (TLS). This presentation features a national thought leader, Mitchell S. Cairo, MD, who provides key insights.

Acknowledgment of Commercial Support

This activity is supported by an educational grant from Sanofi Genzyme.

 

Instructions for This Activity and Receiving Credit

  • You will need to login to participate in the activity.
  • Each presentation may contain an interactive question(s). You may move forward through the presentation; however, you may not go back to change answers or review videos/content until you finish the presentation.
  • At the end of the activity, “educational content/video files” will be available for your reference.
  • In order to receive a CME certificate, participants must complete the activity.
  • Complete the posttest and pass with a score of 70% or higher, complete the evaluation and then click on request for credit. Participants may immediately download a CME certificate upon completion of these steps.


Target Audience

This educational initiative is directed toward medical oncologists and hematologists who treat patients with TLS. Nephrologists, nurse practitioners, nurses, physician assistants, pharmacists, researchers, fellows, and other healthcare professionals interested in the treatment and prevention of TLS are also invited to participate.

Educational Objectives

Upon completion of this activity, you should be better prepared to:

  • Describe risk factors and appropriate stratification of pediatric and adult patients who could potentially develop tumor lysis syndrome (TLS)
  • Compare and contrast optimal TLS preventive and treatment strategies for low- and high-risk patients with cancer
  • Apply clinical evidence and expert guidance in TLS prophylaxis and treatment
Faculty
Mitchell S. Cairo
Mitchell S. Cairo, MD
Chief, Pediatric Hematology, Oncology and Stem Cell Transplantation
Director, Children and Adolescent Cancer and Blood Diseases Center
Medical and Scientific Director, WMC Cellular and Tissue Engineering Laboratory
Medical Director, Westchester Medical Center Hematotherapy Program
Associate Chairman, Department of Pediatrics
Professor of Pediatrics, Medicine, Pathology, Microbiology & Immunology and Cell Biology & Anatomy
Maria Fareri Children’s Hospital
Westchester Medical Center
New York Medical College
New York, NY

Disclosure: Dr. Cairo has no relevant financial relationships with commercial interests to disclose.

The staff of Physicians' Education Resource®, LLC have no relevant financial relationships with commercial interests to disclose.

Disclosure Policy and Resolution of Conflicts of Interest (COI)

As a sponsor accredited by the ACCME, it is the policy of PER® to ensure fair balance, independence, objectivity, and scientific rigor in all of its CME activities. In compliance with ACCME guidelines, PER® requires everyone who is in a position to control the content of a CME activity to disclose all relevant financial relationships with commercial interests. The ACCME defines “relevant financial relationships” as financial relationships in any amount occurring within the past 12 months that creates a COI.
 
Additionally, PER® is required by ACCME to resolve all COI. PER® has identified and resolved all COI prior to the start of this activity by using a multistep process.

Off-Label Disclosure and Disclaimer

This CME activity may or may not discuss investigational, unapproved, or off-label use of drugs. Participants are advised to consult prescribing information for any products discussed. The information provided in this CME activity is for continuing medical and nursing education purposes only, and is not meant to substitute for the independent clinical judgment of a physician or nurse relative to diagnostic, treatment, or management options for a specific patient’s medical condition.

The opinions expressed in the content are solely those of the individual faculty members and do not reflect those of PER®.

PER Pulse™ Recaps

1 of 3
Insight from Mitchell S. Cairo, MD—PER Pulse™ Recap:
Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis Syndrome

The online continuing medical education activity Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis Syndrome assesses recent data in tumor lysis syndrome (TLS) for adult and pediatric patients. You will consider preventive and treatment strategies in both the high-risk and low-risk patient populations to provide optimal care to your patients. Clinical perspective and key insights are provided by national thought leader Mitchell S. Cairo, MD.

This first of 3 PER Pulse™ Recaps for the activity will focus on clinical evidence for the treatment of TLS in adult and pediatric patients. Below are some highlights from the activity featuring Dr. Cairo:

TLS is a life-threatening oncologic emergency that can occur spontaneously or in response to anticancer chemotherapy or biotherapy.1,2

“Newer agents such as fludarabine, antibody-related new drugs blinatumomab, inotuzumab, rituximab, and the BCL2 inhibitor venetoclax—all those new agents that have come into the treatment armamentarium in the past couple of years have increased the incidence of tumor lysis.”
—Mitchell S. Cairo, MD

In combating TLS-associated hyperuricemia, allopurinol may be used to block the conversion of xanthine and hypoxanthine to uric acid. In a retrospective analysis of 1172 patients with elevated uric acid levels, intravenous allopurinol reduced uric acid levels in 57% of adult patients (mean time to response, 5 days) and stabilized levels in an additional 30% (mean time to response, 2 days).3 In pediatric patients, uric acid levels improved in 88% of patients and stabilized in 7% (mean time to response, 1 day in both cases). When used prophylactically in patients at risk of developing TLS, it prevented an increase in serum uric acid levels in 93% of adults and 92% of children.3 Although allopurinol has demonstrated efficacy in preventing and treating hyperuricemia, it is ineffective in reducing levels of uric acid developed before treatment, and it can lead to a buildup and precipitation of xanthine crystals in the renal tubules, potentially leading to acute obstructive uropathy.

However, rasburicase, a recombinant urate oxidase, has proved to be more effective than allopurinol for the prevention and treatment of TLS by directly degrading uric acid into allantoin and preventing xanthine accumulation.4 In a clinical study by Cortes and colleagues,5 in which adults with hematologic malignancies at risk of hyperuricemia and TLS were randomly assigned to rasburicase (0.20 mg/kg/day intravenously, days 1-5), rasburicase plus allopurinol (rasburicase 0.20 mg/kg/day, days 1-3, followed by oral allopurinol 300 mg/day, days 3-5), or allopurinol (300 mg/day, days 1-5), the plasma uric acid response rate was 87% with rasburicase, 78% with rasburicase plus allopurinol, and 66% with allopurinol. Rasburicase provided more control over the plasma uric acid and did so more rapidly than allopurinol. To enhance the agent’s safe usage, clinicians should screen patients for pregnancy and glucose-6-phosphate dehydrogenase deficiency, given the contraindication for rasburicase in these populations.

Rasburicase continues to be evaluated for its safety and effectiveness. A recent study of 67 patients with lymphoid malignancies at high risk of TLS who were treated with a single dose of rasburicase as prophylaxis found the agent to be highly effective in preventing the progression of TLS (incidence of 3%), irrespective of any risk factors, including increased creatinine clearance.6 In terms of its cost-effectiveness, compared particularly with that of other therapies, results of a recent study revealed that patients with TLS who received rasburicase versus allopurinol (n = 26 and n = 104, respectively) experienced less hyperuricemia, and the treatment was associated with significantly shorter intensive care unit and overall hospital stays; it also was linked to decreased inpatient costs.4 A recent meta-analysis found rasburicase 6 mg to be effective and cost-efficient for adults and the 1.5-mg and 0.15-mg/kg single doses to be appropriate for children.7

References

  1. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359-E386. doi: 10.1002/ijc.29210.
  2. Mirrakhimov AE, Voore P, Khan M, Ali AM. Tumor lysis syndrome: a clinical review. World J Crit Care Med. 2015;4(2):130-138. doi: 10.5492/wjccm.v4.i2.130.
  3. Smalley RV, Guaspari A, Haase-Statz S, Anderson SA, Cederberg D, Hohneker JA. Allopurinol: intravenous use for prevention and treatment of hyperuricemia [erratum in J Clin Oncol. 2000;18(10):2188]. J Clin Oncol. 2000;18(8):1758-1763. doi: 10.1200/JCO.2000.18.8.1758.
  4. Cairo MS, Thompson S, Tangirala K, Eaddy MT. A clinical and economic comparison of rasburicase and allopurinol in the treatment of patients with clinical or laboratory tumor lysis syndrome. Clin Lymphoma Myeloma Leuk. 2017;17(3):173-178. doi: 10.1016/j.clml.2016.11.003.
  5. Cortes J, Moore JO, Maziarz RT, et al. Control of plasma uric acid in adults at risk for tumor lysis syndrome: efficacy and safety of rasburicase alone and rasburicase followed by allopurinol compared with allopurinol alone—results of a multicenter phase III study. J Clin Oncol. 2010;28(27):4207-4213. doi: 10.1200/JCO.2009.26.8896.
  6. Jeon YW, Kwak DH, Park SS, et al. Effectiveness of single-dose rasburicase in patients with lymphoid malignancies at a high risk for tumor lysis syndrome. Clin Lymphoma Myeloma Leuk. 2017;17(9):595-603. doi: 10.1016/j.clml.2017.06.027.
  7. Yu X, Liu L, Nie X, et al. The optimal single-dose regimen of rasburicase for management of tumour lysis syndrome in children and adults: a systematic review and meta-analysis. J Clin Pharm Ther. 2017;42(1):18-26. doi: 10.1111/jcpt.12479.

2 of 3
Insight from Mitchell S. Cairo, MD—PER Pulse™ Recap:
Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis Syndrome

As a follow-up to the online continuing medical education activity Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis Syndrome, this second of 3 PER Pulse™ Recaps for the activity will focus on risk stratification for patients who could develop tumor lysis syndrome (TLS) and the benefit of a multidisciplinary approach for treatment and management. Below are some highlights from the meeting featuring Dr. Cairo:

Because TLS is potentially fatal, close monitoring of patients at risk before, during, and after their course of chemotherapy is crucial.1

“[Although] the oncologist is usually the one who is the primary manager in prevention and treatment, it’s always important to involve the nephrologist as early as possible in a partnership. I can’t emphasize enough the multidisciplinary approach that should be taken.”
—Mitchell S. Cairo, MD

Many patients with TLS will develop acute kidney injury and require either hemodialysis or venous filtration, so it is important to familiarize the nephrologist with your patients as early as possible.

Because of the rapid progression and potential severity of common clinical consequences associated with TLS, risk stratification is an imperative component of directing prevention methods. An international TLS expert consensus panel of pediatric and adult oncologists, experts in TLS pathophysiology, and experts in TLS prophylaxis and management developed a model of TLS classification for low-, intermediate-, and high-risk categories.1 Patients were first assessed for the presence of laboratory TLS: ≥2 increased abnormalities of uric acid, potassium, or phosphate, followed by the classification of hematologic malignancies or solid tumors as low-risk, intermediate-risk, or high-risk disease.1 Patients were stratified by age and stage, bulk disease, white blood cell count, and lactate dehydrogenase level; final adjustments were made based on renal function and involvement to classify risk of developing TLS.1

Prompt identification of at-risk patients and appropriate prophylactic treatment are essential in minimizing clinical consequences. Low-risk patients are typically treated with hydration and allopurinol. Febuxostat can be used in patients intolerant of allopurinol, whereas high-risk patients are usually given hydration and rasburicase in an inpatient setting. Clinicians must be aware of the importance of initiating TLS treatment immediately to correct all issues before starting cancer therapy. They must know to begin with assessing individual patient risk level for TLS and then to follow through with choosing the best treatment option based on that particular risk level.

Reference

  1. Cairo MS, Coiffier B, Reiter A, Younes A; TLS Expert Panel. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010;149(4):578-586. doi: 10.1111/j.1365-2141.2010.08143.x.

3 of 3
Insight from Mitchell S. Cairo, MD—PER Pulse™ Recap:
Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis Syndrome

As a follow-up to the online continuing medical education activity Oncology Briefings™: Current Perspectives on Preventing and Managing Tumor Lysis Syndrome, this third of 3 PER Pulse™ Recaps for the activity will focus on at-risk patient populations and monitoring of symptoms of tumor lysis syndrome (TLS). Below are some highlights from the meeting featuring Dr. Cairo:

Patients with tumors that have the most rapid proliferation rates are those at highest risk of developing TLS.1 The predominant group of tumors that fall into that category is a subgroup of hematologic malignancies, including high-grade B-cell lymphomas such as Burkitt lymphoma, very high-grade diffuse large B-cell lymphoma, acute lymphocytic leukemia, acute myeloid leukemia, and other forms of non-Hodgkin lymphoma, including lymphoblastic lymphoma.

The second major risk factor is the actual tumor burden, which can be reflected by the white blood count or the lactate dehydrogenase level. The third major risk factor is preexisting renal dysfunction that developed prior to the cancer. The fourth major risk factor is the medications that the patient is taking.

Monitoring of patients with TLS includes laboratory testing. Testing methodologies can affect the laboratory values in patients treated with rasburicase.

“In patients who receive rasburicase—because there is continuing, ongoing enzymatic degradation of the uric acid—when the sample is drawn, it should be immediately put on ice and stay on ice until it is tested in the chemistry laboratory. Otherwise, it will falsely continue lowering the uric acid concentration.”
—Mitchell S. Cairo, MD

Monitoring of patients should continue for the entire duration of risk. For patients at risk of TLS and in whom the syndrome has developed, urine output is the key monitoring factor.2 High-risk patients should also receive nursing care with cardiac monitoring and measurement of electrolytes, creatinine, and uric acid every 4 to 6 hours after the start of therapy; intermediate-risk patients should undergo laboratory testing every 8 to 12 hours; and low-risk patients should undergo monitoring daily.2

References

  1. Cairo MS, Coiffier B, Reiter A, Younes A; TLS Expert Panel. Recommendations for the evaluation of risk and prophylaxis of tumour lysis syndrome (TLS) in adults and children with malignant diseases: an expert TLS panel consensus. Br J Haematol. 2010;149(4):578-586. doi: 10.1111/j.1365-2141.2010.08143.x.
  2. Howard SC, Jones DP, Pui C-H. The tumor lysis syndrome [erratum in N Engl J Med. 2018;379(11):1094]. N Engl J Med. 2011;364(19):1844-1854. doi: 10.1056/NEJMra0904569.

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