In 2014, idelalisib, an oral PI3Kδ (phosphoinositide 3-kinase delta) inhibitor, was approved in combination with rituximab for refractory/relapsed (RR) Chronic Lymphocytic Leukaemia (CLL). Idelalisib has significant activity in the treatment naïve and RR setting, including those with poor prognostics (17p-/TP53 mutated). In published trials idelalisib has a manageable adverse event profile. However, there have been subsequent safety concerns pertaining to infection-related mortality, Cytomegalovirus (CMV) reactivation, Pneumocystis jiroveci pneumonia (PJP), hepatitis, pneumonitis, intestinal perforation and colitis. There is a paucity of real life data.


To present "real world" data, detailing Event Free Survival (EFS) and treatment-related toxicities, in patients receiving idelalisib based therapy.


Data was collected retrospectively via a standardised data capture form. All prescribing centres (n=112) within the United Kingdom (UK) and Republic of Ireland (ROS) were contacted by email. Trial patients were included. Poor prognostic disease was defined as 17p-, TP53 mutated, 11q- or ATM deleted. It was not possible to document IWCLL response due to selective re-staging. Minimum duration of treatment for inclusion was 3 months.


Sixty-eight patients were analysed, treated between April 2013 to July 2017. Median age was 77 years (range: 50 - 91), 46/68 being male. Median number of prior therapies was 2 (range: 0-7; 9 first line), including rituximab, fludarabine, alemtuzumab and bendamustine. The majority (51/68) had good performance status (Eastern Cooperative Oncology Group 0/1). TP53 mutated/17p- disease accounted for 26/68 (38%), and 11q-/ATM mutated 9/68 (13%; 3 additional TP53 mutations).

Median duration of treatment was 12 months (range 3-49), of which 24% (16/68) completed ≥24 months of treatment. Three patients (4%) had no response.

Disease-related cytopenias, irrespective of a persisting lymphocytosis, resolved in 78% (51/65), 82% (51/62) and 88% (42/48) at 3, 6 and 12 months. Radiological CR/PR was reported in 71% (PR 10/21; CR 5/21), 70% (11/27 PR; 8/27 CR) and 69% (4/16 PR; 7/16 CR) at 3, 6 and 12 months respectively. Only 1 patient progressed radiologically within the first 6 months. Bone marrow CR/PR was reported in 64% (7/14 PR; 2/14 CR), 69 % (6/17 PR; 5/16 CR) and 75% (3/8 PR; 3/8 CR) at 3, 6 and 12 months.

Median EFS (defined as progression, death [including post-Idelalisib discontinuation] or treatment discontinuation) was 15 months (low risk 14 months; high risk 16 months; p=0.3). Sixty-five percent (44/68) of the cohort remained on therapy at 12 months, 22% (15/68) ≥24 months.

Diarrhoea/colitis was the commonest toxicity, 22/68 patients (32%), of which half were grade ≥3. Toxicities include haematological 28% (5/19 grade≥3), rash 19% (3/13 grade≥3), hepatotoxicity 19% (4/13 grade≥3), pneumonitis 14% (n=10), PCP infection 7% (n=5, prophylaxis regime unclear) and CMV reactivation 4% (n=3; no CMV infection pre-Idelalisib).

Treatment interruption due to drug toxicity was reported in 32/68 patients (diarrhoea/colitis n=10; infections n=11). The median number of drug interruptions was 1 (range: 1-4), median duration off therapy 30 days (range: 7 - 180). In 37/68 patients (54%) idelalisib was discontinued (n=12 progression; n=13 diarrhoea/colitis; n=6 recurrent infection; pneumonitis n=4; hepatotoxicity n=2). Twenty deaths (29%) were recorded but only 3 occurred on Idelalisib (1 therapy-related). Nine of 12 patients that had progressed died at time of analysis.


We report one of the first "real-world" cohorts treated with idelalisib. This was a relatively elderly multiply treated population, although with good performance status, 51% had poor prognostics which did not confer an inferior outcome. Median number of cycles was 12 (admixed - first line/relapsed) with an EFS of 15 months. Median treatment duration has been reported up to 22.4 months in the up-front setting (O'Brien et al. 2015; Blood). Thirty seven percent of patients discontinued therapy due to toxicity, mostly due to diarrhoea/colitis, comparable to other publications (Thompson et al. 2016; Cancer). Risk profile can be reduced with PCP prophylaxis, CMV surveillance and following consensus guidelines on toxicity management. Idelalisib remains an efficacious treatment for CLL, with 22% of the cohort continuing on therapy at 24 months.


Patten: Gilead Inc: Honoraria, Research Funding; Roche: Honoraria; Abbvie: Honoraria. Gohil: UCL Business: Patents & Royalties. Iyengar: Gilead Inc: Honoraria; Janssen: Honoraria. Nathwani: UCL Business: Patents & Royalties. Heath: Gilead Inc: Honoraria. Ayto: Gilead Inc: Honoraria.

Author notes


Asterisk with author names denotes non-ASH members.