Incidence and risk of tumor lysis syndrome in patients with relapsed chronic lymphocytic leukemia (CLL) treated with venetoclax in routine clinical practice

Abstract

The risk of TLS in patients with relapsed CLL treated outside of clinical trials is not well described. Using the Mayo Clinic CLL Database, 48 patients treated with venetoclax for relapsed CLL in routine practice were identified; chart review determined baseline risk for TLS and laboratory abnormalities during venetoclax ramp-up. Overall, 6 (13%) patients developed laboratory TLS, 3 of whom demonstrated clinical TLS. The majority of patients who developed TLS were stratified as low or medium risk by the package insert. Of the 42 patients who did not meet Howard criteria for TLS, isolated hyperphosphatemia occurred in 19 patients (45%), hyperkalemia in 13 patients (31%), hyperuricemia in 2 patients (5%), and hypocalcemia in 1 patient (2%). In routine practice, the incidence of TLS appears higher than reported in clinical trials (3–6%). Half of patients who did not meet criteria for TLS developed clinically significant electrolyte abnormalities that required medical intervention.

Keywords:

• Chronic Lymphocytic Leukemia (CLL)
• venetoclax
• Tumor Lysis Syndrome (TLS)

Acknowledgments

The authors would like to thank the participating patients treated at Mayo Clinic. The results of this study were presented as a poster at the International Workshop on Chronic Lymphocytic Leukemia in Edinburgh, Scotland in September 2019. The conduct of this research was supported in part by the Henry J Predolin Foundation. This project was supported in part by a grant from the Mayo Clinic K2R Career Development Program awarded to Sameer A. Parikh.

Author Contributions

ABK and SAP designed the research, collected, analyzed and interpreted data, and wrote the manuscript.

NL, TGC, WD, SSK, JFL, YW, EM, SRH, and NEK cared for the patients and critically reviewed the manuscript.

KGR, SJA, SMS, and SLS collected and analyzed data, conducted statistical analysis, and critically reviewed the manuscript.

All authors approved the manuscript in its final format.

Disclosure statement

SAP: Research funding has been provided to the institution from Pharmacyclics, MorphoSys, Janssen, AstraZeneca, TG Therapeutics, Celgene, AbbVie, and Ascentage Pharma for clinical studies in which Sameer A. Parikh is a principal investigator. Sameer A. Parikh has also participated in Advisory Board meetings of Pharmacyclics, AstraZeneca, Genentech, Gilead, GlaxoSmithKline, Verastem Oncology, and AbbVie (he was not personally compensated for his participation).

NEK: Research funding has been provided to the institution from Pharmacyclics, Acerta, Tolero & MEI Pharma for which Neil E. Kay is a principal investigator. Dr. Kay has also participated as a member of the Data and Safety Monitoring Board for Cytomx Therapeutics, Infinity Pharm, Agios Pharm, Celgene, and MorphoSys. He has also participated in Advisory Board meetings of Pharmacyclics and Janssen.

WD: Research funding has been provided to the institution from Merck for which Wei Ding is a principal investigator.

SSK: Sponsored Research Funding provided to the laboratory from Novartis, Kite, Actinium, Morphosys, Lentigen, Humanigen and Tolero. SSK is inventor on patents licensed to Novartis and Humanigen. SSK is a co-founder of LeahLabs and SensImmune and he has participated as a consultant to Leahlabs and Kiniska.

All other authors have no conflict of interest to report.