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 (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.

A unique presentation of destructive shoulder arthropathy in the chronic phase of chronic myeloid leukaemia.

We present a previously unreported case of rapidly progressing, destructive shoulder arthropathy as an initial presentation of chronic phase chronic myeloid leukaemia. This patient initially presented to clinic for consideration of an arthroplasty for symptom relief; however, her loss to follow-up yielded a rapid progression of her symptoms. Bone marrow aspirate and targeted biopsy of the humeral head excluded blast cell crisis, in contrast to previously reported cases. She was treated conservatively with medical management of her underlying disease. Although leukaemic arthritis is a recognized phenomenon, chronic myeloid leukaemia is not known to cause bone destruction of this kind, particularly in the absence of blast crisis. Medical treatment with a tyrosine kinase inhibitor provided a dramatic improvement in our patient's pain, without the risk of attempted arthroplasty in unknown bone quality. We describe a unique presentation of severe bone destruction as a manifestation of chronic myeloid leukaemia in the absence of blast crisis. This should be considered as a rare differential diagnosis in joint arthropathy and may be appropriately managed initially with medical therapy, whereas future arthroplasty comprises uncharted territory in unknown bone quality.