Evidence from clinical practice has shown that an outpatient ramp-up schedule for venetoclax treatment in patients with CLL can safely mitigate the risk of tumour lysis syndrome (TLS).

To address the variability in current practice, haematologists in the UK conducted a multicentre, retrospective, observational study to assess patterns of TLS monitoring as well as the safety of outpatient monitoring practice in CLL patients.

The study, published in the British Journal of Haematology, involved 170 patients with CLL who were treated as per a venetoclax ramp-up schedule at 11 CLL centres. Patients were largely male (60%) with a median age of 69 years, and just over one quarter (27%) of the cohort had baseline renal impairment.

Data revealed TLS events in six patients (3.5%; two clinical and four biochemical), which equated to an incidence of clinical TLS of 1.1%, the researchers noted.

The majority of TLS events occurred in high-risk patients (5; 83%), while 4 (57%) were observed during the first stage of venetoclax ramp-up. Three TLS events were recorded at 6 hours post dose monitoring, while three occurred at 24 hours.

In the group at high risk of TLS, the respective incidence of biochemical TLS and clinical TLS was 7.5% and 5%, and when researchers analysed the risk by inpatient versus outpatient monitoring, TLS was observed in 15% (four of 26) and 8% (one of 13), respectively.

On efficacy, retrospective analysis also showed a complete response rate of 46% and a partial response rate of 39%, with 48% of patients achieving negative MRD during follow-up, according to the paper.

“We provide evidence for a manageable TLS risk with exclusive outpatient ramp-up schedule across all risk groups,” the authors said in their paper.

“This is of particular relevance for patients with a high risk of TLS and suggests that this subgroup can safely be escalated without the need of hospital inpatient bed utilisation.”

The researchers also identified common factors at CLL centres where outpatient ramp-up of venetoclax was feasible, including dedicated CLL/haematology nurse specialists, timely availability of acute hospital admission beds, and a laboratory able to quickly turnaround blood tests during working hours.

They also noted that in the real-world setting an “unexpectedly high” proportion of patients at low risk for TLS were being escalated to ramp-up therapy as inpatients.

Key limitations of the research included a low number of TLS events and potential selection bias.

However, “provided appropriate infrastructure and staffing levels permitting it, we provide evidence of relative safety of the outpatient escalation for venetoclax and validate the effectiveness of the venetoclax ramp-up scheme mitigating TLS risk in this context,” the researchers noted.