Venetoclax + obinutuzumab for chronic lymphocytic leukaemia: Is stringent TLS monitoring proportional to risk?

Background: Venetoclax + obinutuzumab (VenO) has been available as a first line treatment option for CLL in England since 2021. Although well tolerated, stringent tumour lysis syndrome (TLS) monitoring during venetoclax dose escalation, and risk of obinutuzumab-associated infusion related reactions (IRRs) can make treatment initiation onerous. We aimed to review adverse events and TLS monitoring frequency during the first two cycles of VenO for patients treated at a single NHS site. Methods: In this retrospective study we collected data on consecutive patients treated with VenO at Gloucestershire Hospitals between May 2021 and October 2023. The primary outcome was the rate of venetoclax induced biochemical and clinical TLS. Secondary outcomes included the rate of obinutuzumab IRRS requiring unplanned hospital admission and/or treatment delay. Results: In total, 28 patients initiated VenO. At baseline, median age was 69 years (range 35–80), Eastern Cooperative Oncology Group (ECOG) performance status was ≥2 in 4 patients (14%), median lymphocyte count was 145 × 109/L (range 6–675), 10 patients (36%) had maximum lymph node diameter >5 cm and 21 patients (75%) had estimated glomerular filtration rates (eGFR) <80 mL/min. Post obinutuzumab pre-phase and pre-first dose venetoclax, median lymphocyte count dropped to 1.7 × 109/L (range 0.34–12.2). Seven patients (25%) commenced venetoclax as an inpatient for additional monitoring. All patients received allopurinol or rasburicase prophylaxis and had TLS monitoring bloods, as minimum, at 6 and 24 h post venetoclax 50 and 100 mg dose initiation. Twelve patients (43%) continued TLS monitoring for 200 mg, and 6 patients (21%) for 400 mg dose initiation. In total, there was one case of biochemical TLS following 50 mg dose initiation in a high-risk patient which resolved by 24 h following IV hydration. There were no episodes of clinical TLS. In 21 patients receiving first obinutuzumab as an outpatient, 4 (19%) required unplanned admission due to IRRs. Of seven electively admitted for their first dose, three experienced adverse effects that delayed subsequent therapy (IRR = 2; TLS = 1). Conclusion: The low frequency of venetoclax related TLS observed in this study illustrates the success of obinutuzumab loading and venetoclax dose escalation in mitigating against TLS. It suggests that current TLS monitoring recommendations are excessive relative to actual risk. Results suggest that first dose obinutuzumab poses a significantly higher risk to patients and encourages judicious elective admissions. A large scale, multi-site retrospective study is recommended to consolidate the findings of this study.

Citation

Mayo T., Bond A., Wheeler M., Lush R. & McCulloch R. (2024). Venetoclax + obinutuzumab for chronic lymphocytic leukaemia: Is stringent TLS monitoring proportional to risk?. British Journal of Haematology, 204(Supplement 1), 201-202. https://doi.org/10.1111/bjh.19399

DOI

10.1111/bjh.19399

URI

https://hdl.handle.net/20.500.14709/1242

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