High tumor burden
Elevated uric acid
levels at baseline
Elevated WBC count
Renal disease or renal
involvement by tumor
This is not a comprehensive list of all potential risk factors.
Patients with normal uric acid levels may be at significant risk4
Relationship between uric acid level and development of TLS in patients with hematologic malignancies4*
*Results from a retrospective analysis conducted to determine the relationship between uric acid levels and TLS in 1198 patients with a hematologic malignancy who were admitted for inpatient chemotherapy.
Certain anticancer agents have been associated with elevated uric acid or TLS6-19
Agents treating hematologic malignancies associated with risk of increasing uric acid or TLS6-19†
§There is an increased risk of severe skin toxicity when bendamustine HCl is used concomitantly with allopurinol.
Venetoclax therapy and TLS
The National Comprehensive Cancer Network (NCCN®) has specifically developed a set of supportive care recommendations for TLS in patients with CLL or SLL who have been prescribed venetoclax therapy1
- Venetoclax can cause a rapid reduction of the tumor, thus increasing risk for TLS6
- In patients with CLL who followed the current (5 week) dose ramp-up and the TLS prophylaxis and monitoring measures, the rate of TLS was 2% in the venetoclax CLL monotherapy studies. With a 2 to 3 week dose ramp-up and higher starting dose in patients with CLL/SLL, the TLS rate was 13% and included deaths and renal failure6
- The risk of TLS is a continuum based on multiple factors, including tumor burden and comorbidities. Patients should be assessed for risk and should receive appropriate prophylaxis for TLS, including hydration and antihyperuricemics. Monitor blood chemistries and manage abnormalities promptly. Interrupt dosing if needed. Employ more intensive measures (intravenous hydration, frequent monitoring, hospitalization) as overall risk increases6
- Please refer to venetoclax package insert for additional management considerations
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend TLS prophylaxis and monitoring based on tumor burden in patients with CLL/SLL receiving venetoclax1:
- Management of patients with CrCl <80 mL/min and medium tumor burden (any lymph node 5 cm to <10 cm or ALC ≥25 x 109/L) as high risk for TLS
- Consider rasburicase for patients with both high tumor burden and elevated baseline uric acid‖
‖In patients receiving venetoclax therapy, high tumor burden is defined as any lymph node ≥10 cm or ALC ≥25 x109/L and any lymph node ≥5 cm.
Certain malignancies are associated with increased risk for TLS
Patients with (but not limited to) these hematologic malignancies may be at risk for TLS2:
- Acute Iymphoblastic leukemia (ALL)
- Acute myeloid leukemia (AML)
- Chronic myeloid leukemia (CML)
- Burkitt lymphoma (BL)
- Diffuse large B-cell lymphoma (DLBCL)
- Multiple myeloma (MM)
- Chronic lymphocytic leukemia (CLL)
References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma. V.1.2021. ©National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed September 28, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. Wilson FP, Berns JS. Onco-nephrology: tumor lysis syndrome. Clin J Am Soc Nephrol. 2012;7(10):1730-1739. 3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas. V.4.2020. ©National Comprehensive Cancer Network, Inc. 2020. All rights reserved. Accessed August 26, 2020. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 4. Cairo MS. Prevention and treatment of hyperuricemia in hematological malignancies. Clin Lymphoma. 2002;3(S1):S26-S31. 5. Edeani A, Shirali A. Chapter 4: Tumor Lysis Syndrome. Onco-Nephrology Curriculum. American Society of Nephrology. 2016. https://www.asnonline.org/education/distancelearning/curricula/onco/Chapter4.pdf. Accessed August 26, 2020. 6. Venclexta [prescribing information]. East Windsor, NJ: Acrotech Biopharma LLC; 2020. 7. Sprycel [prescribing information]. Princeton, NJ: Bristol-Myers Squibb Company; 2018. 8. Imbruvica [prescribing information]. Sunnyvale, CA: Pharmacyclics LLC; 2020. 9. Marqibo [prescribing information]. South San Francisco, CA: Talon Therapeutics; 2020. 10. Gazyva [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2020. 11. Blincyto [prescribing information]. Thousand Oaks, CA: Amgen Inc.; 2020. 12. Velcade [prescribing information]. Cambridge, MA: Millennium Pharmaceuticals, Inc; 2019. 13. Adriamycin [prescribing information]. Bedford, OH: Bedford Laboratories; 2013. 14. Kyprolis [prescribing information]. Thousand Oaks, CA: Onyx Pharmaceuticals, Inc.; 2020. 15. Revlimid [prescribing information]. Summit, NJ: Celgene Corporation; 2019. 16. Rituxan [prescribing information]. South San Francisco, CA: Genentech, Inc.; 2020. 17. Bendeka [prescribing information]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; 2019. 18. Belay Y, Yirdaw K, Enawgaw B. Tumor lysis syndrome in patients with hematological malignancies. J Oncol. 2017. doi.org/10.1155/2017/9684909. 19. Bose P, Qubaiah O. A review of tumour lysis syndrome with targeted therapies and the role of rasburicase. J Clin Pharm Ther. 2011;36(3):299-326.