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)

Abstract

Summary Idelalisib (IDL) is an oral first‐in‐class phosphatidylinositol 3‐kinase delta (PI3Kδ) 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 30·2 (0·1–51·9) months. The median (range) age was 72 (48–89) years. Tumour protein p53‐disruption was common [100% 1L, 32·5% relapsed/refractory (R/R)]. The best ORR (intention‐to‐treat) was 88·2% (1L 96·3%, R/R 85·5%). Overall, the median event‐free survival (mEFS) was 20·3 months and time‐to‐next treatment was 29·2 months. The mEFS for 1L patients was 18·7 months and R/R patients was 21·7 months. The 3‐year overall survival was 56·1% (95% confidence interval 45·7–65·3). IDL was discontinued in 87·3% (n = 96). More patients discontinued due to adverse events in the front‐line setting (1L 63·0% vs. R/R 44·6%) and due to progressive disease in R/R patients (20·5% vs. 3·7% in 1L). Lower respiratory tract infection/pneumonia were reported in 34·5% (Grade ≥3, 19·1%), diarrhoea in 30·9% (Grade ≥3, 6·4%), and colitis in 9·1% (Grade ≥3, 5·5%). 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.

Searching for a home: phosphoinositide 3‐kinase inhibitors for chronic lymphocytic leukaemia in modern clinical practice

“…While Eyre et al 1 report an EFS of 17Á3 months in this combined front-line and relapsed population, importantly only a small minority of patients in this series had prior Bruton tyrosine kinase inhibitor (BTKi) exposure (6%) and none had prior venetoclax exposure. This raises the important question of whether the results from this study (and the prior studies which led to the approvals of idelalisib and duvelisib) are generalisable to current clinical practice, where most patients will be treated with two prior targeted therapies before consideration of a PI3K inhibitor.…”

“…While Eyre et al 1 . report an EFS of 17·3 months in this combined front‐line and relapsed population, importantly only a small minority of patients in this series had prior Bruton tyrosine kinase inhibitor (BTKi) exposure (6%) and none had prior venetoclax exposure.…”

“…In this issue of British Journal of Haematology , Eyre et al 1 . present retrospective data on 110 patients with chronic lymphocytic leukaemia (CLL) treated with idelalisib and rituximab in the UK and Ireland.…”

“…In this issue of British Journal of Haematology, Eyre et al 1 present retrospective data on 110 patients with chronic lymphocytic leukaemia (CLL) treated with idelalisib and rituximab in the UK and Ireland. We commend the authors for this valuable addition to the growing real-world literature on use of phosphoinositide 3-kinase (PI3K) inhibitors in CLL.…”

“…While PI3K inhibition results in effective targeting of CLL cells, toxicities limit widespread use of currently approved agents. 2,3 Eyre et al 1 have demonstrated a discontinuation rate of 87% (49% due to toxicity) with median follow up of 30 months and a median event-free survival (EFS) of 20 months. However, despite this high discontinuation rate, the median time-to-next treatment (TTNT) is notable at 29 months.…”