A retrospective observational study to evaluate the clinical outcomes and routine management of patients with chronic lymphocytic leukaemia treated with idelalisib and rituximab in the UK and Ireland (RETRO-idel)

Idelalisib (IDL) is an oral first-in-class phosphatidylinositol 3-kinase delta (PI3K delta) inhibitor approved for chronic lymphocytic leukaemia (CLL) alongside rituximab (R) since 2014. However, little data exist on routine practice. The RETRO-idel was a protocol-led, retrospective study of 110 patients [n = 27 front-line (1L)] who received IDL-R. The primary end-point was clinical overall response rate (ORR). The median (range) follow-up of the whole cohort was 30 center dot 2 (0 center dot 1-51 center dot 9) months. The median (range) age was 72 (48-89) years. Tumour protein p53-disruption was common [100% 1L, 32 center dot 5% relapsed/refractory (R/R)]. The best ORR (intention-to-treat) was 88 center dot 2% (1L 96 center dot 3%, R/R 85 center dot 5%). Overall, the median event-free survival (mEFS) was 20 center dot 3 months and time-to-next treatment was 29 center dot 2 months. The mEFS for 1L patients was 18 center dot 7 months and R/R patients was 21 center dot 7 months. The 3-year overall survival was 56 center dot 1% (95% confidence interval 45 center dot 7-65 center dot 3). IDL was discontinued in 87 center dot 3% (n = 96). More patients discontinued due to adverse events in the front-line setting (1L 63 center dot 0% vs. R/R 44 center dot 6%) and due to progressive disease in R/R patients (20 center dot 5% vs. 3 center dot 7% in 1L). Lower respiratory tract infection/pneumonia were reported in 34 center dot 5% (Grade >= 3, 19 center dot 1%), diarrhoea in 30 center dot 9% (Grade >= 3, 6 center dot 4%), and colitis in 9 center dot 1% (Grade >= 3, 5 center dot 5%). Overall, these data describe clear efficacy for IDL-R in routine practice. No new safety signals were identified, although careful management of known toxicities is required.