Background and Importance Venetoclax acts as an inhibitor of the anti-apoptotic protein Bcl-2, which is increased in Chronic Lymphocytic Leukemia (CLL) and Acute Myeloid Leukemia (AML). It is described on its label the frequent occurrence of haematological toxicity, among other adverse events (AE).
Aim and Objectives 1) To evaluate the haematological toxicity of venetoclax during dose escalation and; 2) To describe AE associated with venetoclax during treatment.
Material and Methods Multicentre, observational, retrospective study in patients who initiated venetoclax until 01/06/2022 with a treatment period ≥ 3 months. Variables collected: sex, age, diagnosis, treatment schedule, hemoglobin, neutrophil and platelet levels at baseline and after dose escalation and; AE developed during treatment appearance as well as its gravity according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Hematologic toxicity during escalation was analysed using Student’s t-test (SPSS Statistics 25.0).
Results 41 patients initiated venetoclax, of whom 33 maintained treatment ≥ 3 months (63.6% male, mean 68.7 ± 9.7 years). Diagnosis (CLL: 20, AML: 10, myelodysplastic syndrome: 3), treatment schedule [monotherapy: 2; bitherapy (rituximab: 16, azacitidine: 13, decitabine: 1, obinutuzumab: 1)]. 5 patients required dose adjustment due to concomitant use of azoles (posaconazole: 2, voriconazole: 2, fluconazole: 1).
Mean hemoglobin at baseline and after dose escalation (10.6 ± 1.9 vs 10.8 ± 2.1g/dL; p=0.282), mean neutrophils at baseline and after dose escalation (1,667.6 ± 1,064.9 vs 1,237.3 ± 1,011.5/µL; p=0.001), mean platelets at baseline and after dose escalation (120,060.0 ± 77,662.3 vs 116,121 ± 77,012.0/mm3; p=0.697). AE developed during treatment: anaemia (G2:3, G3:4), neutropenia (G1:1, G2:6; G3:6, G4:4), thrombocytopenia (G2:1, G3:4), asthenia (G1:2, G3:1), bradycardia (G2:1), diarrhoea (G1:1), fever (G1:1), hypertransaminemia (G2:1), mucositis (G1:1), pneumonia (G2:2, G3:3), tumour lysis syndrome (G3:2). During treatment, 15 patients required discontinuation of treatment (restarts: 7) and 5 required dose reduction.
Conclusion and Relevance During dose escalation, the main haematological toxicity of venetoclax was neutropenia. This adverse effect also occurred more frequently during maintenance treatment. We consider it relevant to carry out serial haematological controls in patients treated with venetoclax.
Limitations of the study: retrospective study with a small sample size; therefore, it is considered necessary to perform more studies to confirm the results presented.
References and/or Acknowledgements 1. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. 27 November 2017.
Conflict of Interest No conflict of interest