Background and importanceIn managing chronic lymphocytic leukaemia (CLL), it is recommended that patients with TP53 deletion/mutation (TP53mut), who have a poor prognosis, are treated with ibrutinib as frontline therapy. Because of severe infectious complications, idelalisib combined with rituximab is only recommended for frontline therapy in patients not suitable for ibrutinib, if measures to prevent infection are followed. Patients unsuitable for ibrutinib/idelalisib may otherwise be treated with venetoclax.Aim and objectivesTo evaluate the prescriptions and clinical outcomes of ibrutinib, idelalisib and venetoclax in a third level hospital.Material and methodsAn observational, retrospective study was conducted including any prescriptions of ibrutinib, idelalisib and venetoclax for CLL from November 2015 to June 2019. We focused on TP53 mutation status, drug exposure, survival outcomes and reasons for drug switching or dose reduction, if applicable. Data were collected from electronic medical records.ResultsThirty patients receiving ibrutinib (n=23), idelalisib (n=13) and/or venetoclax (n=5) were recruited. Seventeen patients (56.7%) showed TP53mut. In the ibrutinib cohort, median drug exposure was 10.5 months and most patients (65.2%) had received it after conventional chemotherapy regimens (eg, FCR, R-CHOP, R-bendamustine). Only 5 patients (21.7%) showing TP53mut had taken ibrutinib as firstline therapy and 4 (17.4%) had received it after idelalisib; 2 of these patients because of disease progression and the other 2 because of adverse events (severe infections and colitis with weight loss). In the idelalisib cohort, median drug exposure was 4.45 months. Venetoclax was used for a median of 0.74 months and on ibrutinib failure in 4 patients (the remaining patient received prior idelalisib due to concomitant anticoagulant therapy). Dose reductions were needed in 11 patients on ibrutinib (causes: bruising, respiratory tract infections and neutropenia); in 4 receiving idelalisib due to severe diarrhoea (n=3) and pneumonia (n=1); and in 1 patient on venetoclax due to severe neutropenia. Neither median progression free survival nor median overall survival were reached at the data cut-off date. In fact, 59.5% of patients were still alive.Conclusion and relevanceMost patients received secondline ibrutinib and showed a long term response duration even when TP53mut was absent. Adverse effects resulted in frequent dose reductions/drug switching. However, venetoclax represents an appropriate option for patients whose CLL has failed to respond to ibrutinib/idelalisib.References and/or acknowledgementsNo conflict of interest.