1106 - Clinical Relevance of the Recommended Intensive Laboratory Monitoring during the Standard Ramp-up at Time of Venetoclax Initiation for CLL: A Real-World Experience

Introduction:
Venetoclax-based treatments are standard of care for treatment of CLL . The requirements for intensive monitoring , which require frequent patient visits, is a limiting factor that has contributed to the relatively low utilization of this effective drug. The clinical relevance of such intensive monitoring strategy in clinical practice, especially in patients with low or medium risk for tumor lysis syndrome (TLS), is unknown. We hypothesized that most of the monitoring labs and visits beyond the first week of the standard 5-week ramp-up (Stilgenbauer S, et al. Lancet Oncol. 2016;17(6):768-778.) do not result in significant clinical findings or interventions.

The aim of this study was to determine the clinical significance of laboratory monitoring for TLS during the standard ramp-up period as indicated by the approved prescription information. The primary endpoint was the incidence of laboratory and clinical TLS and clinical interventions that were done based on the laboratory findings during the ramp-up.

Methods:
We included patients who started venetoclax in the outpatient setting for patients with CLL/SLL from 2016 to 2022. Laboratory and clinical information were reviewed for each dosing during the 5-week ramp-up. Patients with non-standard (escalated) ramp-up, those on clinical trials, or those on concurrent BTK inhibitors were excluded. TLS was defined by Cairo-Bishop criteria (Cairo MS, et al. Br J Haematol. 2004;127(1):3-11.); laboratory abnormalities were documented based on absolute threshold. Clinical interventions based on the laboratory or clinical findings were documented. The study was approved by the institutional IRB.


Results:
A total of 56 patients (25% female) with median age 64 years old (range 39-81) met study criteria. TLS risk categories included 42 low-risk (75%), 13 medium-risk (23%), and 1 high-risk (2%). The majority (59%) received venetoclax in the first-line setting. Forty-six patients (82%) received prior debulking with an anti-CD20 antibody (obinutuzumab 46%, rituximab 54%). At venetoclax initiation, all patients received either allopurinol (98%) or febuxostat (2%). Throughout the ramp-up process, patients received preemptive intravenous fluids (73% week 1, 55% week 2, 34% week 3, and 20% weeks 4 and 5). Overall, no incidence of clinical TLS (neurotoxicity, cardiotoxicity, or renal toxicity) was noted. Criteria for laboratory TLS were met with 1 patient (1.8%) overall. A patient who met laboratory TLS criteria with hyperphosphatemia and hypocalcemia in week 5 was excluded; the patient was on dialysis throughout ramp-up, and there was concern with compliance with nephrologist-directed sevelamer therapy. Three patients exhibited laboratory deviations from normal limits that did not meet Cairo-Bishop criteria [patient 1: day 1 (after venetoclax initiation), week 3, and week 4; patient 2: week 2; and patient 3: week 2]. No patient required anti-hyperuricemic therapy (e.g., rasburicase) nor hospitalization. Only 2 patients (3.6%) received interventions for hyperphosphatemia (weeks 1-3) or hypocalcemia (week 2). Only 1.8% of patients required addition of intravenous fluids during ramp-up for serum creatinine elevation (one during week 4).

Conclusion:
Intensive laboratory monitoring during the 5-week ramp-up in CLL/SLL patients with low or medium-risk TLS resulted in very low rates of laboratory and clinical TLS or clinical interventions. Strategies to modify such requirements need to be considered and can potentially increase the utilization of venetoclax.