Venetoclax and CLL: How Much TLS Monitoring Is Really Necessary?

As a result of significant efficacy and tolerability compared with chemoimmunotherapy for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL), venetoclax has been a commercially available treatment since 2019.^1,2 However, some patients treated with venetoclax develop tumor lysis syndrome (TLS).³ The standard strategy for TLS mitigation is dose escalation and TLS monitoring during dose ramp-up, and there is an ongoing debate on whether intensive TLS monitoring is needed.

“The key message we are conveying is that the labor-intensive tumor lysis monitoring after initiation of venetoclax ramp up in CLL rarely leads to any interventions in low and medium tumor burden patients with CLL and less intensive tumor lysis monitoring may be safe, although this should be verified in a prospective study,” Nilanjan Ghosh, MD, PhD, FACP of Atrium Health Levine Cancer Institute told Blood Cancers Today.

A real-world, single-institution study evaluated adult patients with CLL who started venetoclax therapy between July 2017 and March 2021 at Levine Cancer Institute.³ The study investigators collected information on the incidence of laboratory and clinical TLS and any interventions conducted to mitigate TLS.

Among 73 patients who initiated treatment with venetoclax, there was a low tumor burden in 49% and a medium tumor burden in 44%. Sixty-six percent of patients had TLS monitoring during venetoclax ramp-up in accordance with the venetoclax package insert. Laboratory TLS was observed in one patient, but no patients developed clinical TLS. Unplanned interventions were carried out for six patients as treatment for TLS. Of those who required interventions, all had high or medium tumor burden. No patients with low tumor burden had unplanned interventions.

The real-world data show that interventions are uncommon, and the overall incidence of TLS is low. The findings mirror a retrospective study of 55 patients treated with venetoclax in combination with or without anti-CD20 antibody therapy in the clinical trial setting.⁴ The majority of the patient population had a low risk for TLS.

Results showed no clinical TLS in the cohort, and laboratory TLS only occurred in 1.8% of patients. Antihyperuricemic therapy was not needed for any patient in the cohort, and only 3.6% of patients required interventions for hyperphosphatemia or hypocalcemia. There was a limited need for intravenous fluids (1.8% of patients). Furthermore, no patients were hospitalized.

During venetoclax ramp-up, collective research revealed that overall, intensive monitoring requirements can be reduced.

References

1. FDA approves venetoclax for CLL and SLL. News release. FDA. May 15, 2019. Accessed December 13, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-venetoclax-cll-and-sll
2. Al-Sawaf O, Zhang C, Tandon M, et al. Venetoclax plus obinutuzumab versus chlorambucil plus obinutuzumab for previously untreated chronic lymphocytic leukaemia (CLL14): follow-up results from a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2020;21(9):1188-1200. doi: 10.1016/S1470-2045(20)30443-5
3. Ghosh N, Matusz-Fisher A, Bose R, et al. Evaluation of the impact of monitoring for tumor lysis during venetoclax ramp-up in chronic lymphocytic leukemia in routine clinical practice. JCO Oncol Pract. Published online ahead of print November 18, 2024. doi: 10.1200/OP.24.00417
4. Huang I, Baek G, Cohen J, et al. Clinical relevance of intensive laboratory monitoring with standard venetoclax ramp-up for chronic lymphocytic leukemia: a real-world experience. JCO Oncol Pract. 2024;Nov 18:OP2400416. Online ahead of print. doi: 10.1200/OP.24.00416