Ibrutinib for Relapsed / Refractory CLL: A UK and Ireland Analysis of Outcomes in 315 patients

In 2014, ibrutinib was made available for relapsed/refractory chronic lymphocytic leukaemia (CLL) patients. The UK CLL Forum collected data from UK/Ireland patients with a minimum of 1 year follow-up with pre-planned primary endpoints; the number of patients still on therapy at 1 year (Discontinuation Free Survival; DFS) and 1 year overall survival (OS). With a median 16 months follow-up, data on 315 patients demonstrated 1 year DFS of 73.7% and 1 year OS of 83.8%. Patients with better pre-treatment performance status (PS 0/1 vs 2+) had superior DFS (77.5% vs 61.3%;p14 days and had OS of 89.7%, while 26% of patients had dose reductions and 13% had temporary treatment breaks >14 days. We could not demonstrate a detrimental effect of dose reductions alone (1 year OS: 91.7%), but patients who had first year treatment breaks > 14 days, particularly permanent cessation of ibrutinib had both reduced 1 year OS (68.5%) and also a statistically significant excess mortality rate beyond one year. Although outcomes appear inferior to the RESONATE trial (1 year OS;90%: PFS;84%), this may partly reflect the inclusion of PS 2+ patients and that 17.5% of patients permanently discontinued ibrutinib due to an event other than disease progression

The Impact of Escitalopram on IL-2-Induced Neuroendocrine, Immune, and Behavioral Changes in Patients with Malignant Melanoma: Preliminary Findings

Interleukin (IL)-2, a T-cell cytokine used to treat malignant melanoma, can induce profound depression. To determine whether pretreatment with the antidepressant escitalopram could reduce IL-2-induced neuroendocrine, immune, and neurobehavioral changes, 20 patients with Stage IV melanoma were randomized to either placebo or the serotonin reuptake inhibitor, escitalopram (ESC) 10–20 mg/day, 2 weeks before, and during IL-2 treatment (720 000 units/kg Q8 h × 5 days (1 cycle) every 3 weeks × 4 cycles). Generalized estimation equations were used to examine HPA axis activity (plasma ACTH and cortisol), immune activation (plasma IL-6), and depressive symptoms (Hamilton Depression Rating Scale (HDRS) score). Tolerance of IL-2 treatment (concomitant medications required) and adherence (number of IL-2 doses received) were also assessed. Both the groups (ESC (n=9), placebo (n=11)) exhibited significant IL-2-induced increases in plasma cortisol, IL-6, and depressive symptoms (p<0.05), as well as a temporal trend for increases in plasma ACTH (p=0.054); the effects of age and treatment were not significant. Higher plasma ACTH concentrations were associated with higher depressive symptoms during cycles 1–3 of IL-2 therapy (p<0.01). Although ESC had no significant effects on ACTH, cortisol, IL-6, tolerance of, or adherence to IL-2, ESC treatment was associated with lower depressive symptoms, ie, a maximal difference of ∼3 points on the HDRS, which, though not statistically significant (in part, due to small sample size), represents a clinically significant difference according to the National Institute for Health and Clinical Excellence guidelines. A larger sample size will establish whether antidepressant pretreatment can prevent IL-2-induced neurobehavioral changes