Real-world outcomes upon second-line treatment in patients with chronic lymphocytic leukaemia.

For chronic lymphocytic leukaemia (CLL), targeted drugs have become the standard of care, in particular for second-line treatment. In this study, overall survival (OS), treatment-free survival (TFS) and adverse events (AE) were registered retrospectively in a Danish population-based cohort upon second-line treatment for CLL. Data were collected from medical records and the Danish National CLL register. For 286 patients receiving second-line treatment, three-year TFS was higher upon targeted treatment (ibrutinib/venetoclax/idelalisib) [63%, 95% confidence interval (CI) 50%-76%] compared with fludarabine, cyclophosphamide and rituximab or bendamustine and rituximab (FCR/BR) (37%, CI: 26%-48%) and chlorambucil+/-CD20-antibody (CD20Clb/Clb) (22%, CI: 10%-33%). Upon targeted treatment, three-year OS estimates were higher for targeted treatment (79%, CI: 68%-91%) compared with FCR/BR (70%, CI: 60%-81%) or CD20Clb/Clb (60%, CI: 47%-74%). The most common AEs were infections and haematological AEs; 92% of patients treated with targeted drugs had AEs, 53% of which were severe. Upon FCR/BR and CD20Clb/Clb, AEs were present for 75% and 53% respectively, of which 63% and 31% were severe. These real-world data demonstrate higher TFS and a tendency towards higher OS following targeted second-line treatment for CLL compared to chemoimmunotherapy, also for patients who may be frailer and more comorbid.

The CLL comorbidity index in a population-based cohort: a tool for clinical care and research.

The chronic lymphocytic leukemia comorbidity index (CLL-CI) is an efficient, CLL-specific tool derived from the Cumulative Illness Rating Scale. The CLL-CI is based on the assessment of the organ systems found to be most strongly associated with event-free survival (EFS) in CLL: vascular, upper gastrointestinal, and endocrine, at the time of initiation of CLL therapy. The CLL-CI categorizes patients into low, intermediate, and high risk groups. In the present study, we have employed the CLL-CI in a population-based cohort comprising 4975 patients with CLL. We demonstrate that CLL-CI retains prognostic significance in this large cohort and is associated with overall survival (OS) and EFS from time of first therapy. Furthermore, CLL-CI associates with OS, EFS, and time to first treatment from diagnosis independently of the CLL International Prognostic Index. These findings support the use of the CLL-CI both in research and in clinical practice.

Risk of new malignancies among patients with CLL treated with chemotherapy: results of a Danish population-based study.

Patients with chronic lymphocytic leukaemia (CLL) have an increased risk of new malignancies. However, limited data have been published about the impact of CLL treatment on this risk. Here we followed a Danish population-based cohort of CLL patients for risks of new malignancies. Patients in the Danish CLL registry (2008-2017) were included. Up to 50 CLL-free matched comparators were identified. First-line treatment was categorized into four groups; bendamustine, chlorambucil, fludarabine or other. Patients were followed from CLL diagnosis for individual types of malignancy. Adjusted hazard ratios (HR) for new malignancies and 95% confidence intervals (95% CI) were calculated. Overall, 4286 CLL patients and 214 150 controls developed 594 and 20 565 new malignancies respectively. Risk of new malignancies was increased for CLL patients. Chemotherapy treatment was registered for 1064 (25%) patients with CLL. Chemotherapy was associated with increased HR (1·51, 95% CI: 1·3-1·8) of any new malignancy. Specifically, fludarabine was associated with an increased risk of myelodysplastic syndrome (MDS) (HR 4·93, 95% CI: 1·2-19·8). Patients with CLL are at increased risk of other haematological and solid malignancies compared to the general population. Chemotherapy exposure is associated with increased risk of second malignancies and fludarabine is associated with increased risk of MDS.

Healthcare Utilization and Comorbidity in Chronic Lymphocytic Leukemia.

PURPOSE: Age-related comorbidity is highly prevalent in chronic lymphocytic leukemia (CLL). The purpose of this study was to provide information on current patterns of healthcare utilization in CLL. PATIENTS AND METHODS: We used data from Danish nation-wide registers to study healthcare utilization the year before and the year after CLL diagnosis and in relation to first-line treatment. Patients diagnosed with CLL between 1997 and 2018 were included and stratified on number of comorbidities, presence of specific comorbidities, and fitness status, respectively. Healthcare utilization was studied in terms of hospital admissions, in-hospital bed days, out-patient visits, emergency room visits, and prescription drugs. Odds ratios with 95% confidence intervals were calculated using multivariable logistic regression analyses adjusting for age, sex, and calendar year. RESULTS: The study comprised 9170 patients with CLL with a median age of 71 years, of whom 35% had ≥1 comorbidity. Healthcare utilization increased markedly upon CLL diagnosis both in patients with and without comorbidities. During the year after CLL diagnosis, 39% were hospitalized, 16% visited an emergency room, 88% visited an out-patient clinic, and 93% received prescription drugs. Both individual comorbidities and the total number of comorbidities were associated with increased healthcare utilization of all types, except for contacts to hematological departments. CONCLUSION: Our results suggest that CLL diagnosis may unveil incipient diseases and aggravate comorbidities and thereby have considerably wider health implications than those directly related to CLL. These findings may be used by clinicians and decisions makers to guide planning of multidisciplinary care for cancer patients.