Real-world patterns and sequences of targeted therapy use in chronic lymphocytic leukemia and small lymphocytic lymphoma in the United States: a longitudinal study.

With increasing focus on novel targeted therapies for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), this longitudinal claims-based study evaluated real-world CLL/SLL treatment sequences, particularly sequential targeted therapy. Among patients with first-line (1 L) treatment in 2014-2017 (N = 2,612; median follow-up = 3 years), the most common 1 L treatment was chemoimmunotherapy (CIT; 44.6%), followed by CD20 (25.2%) and Bruton's tyrosine kinase inhibitors (BTKi; 21.7%). Among those with 1 L in 2018-2021 (N = 4,534; median follow-up = 1 year), these were BTKi (45.5%), CD20 (20.4%), CIT (17.5%), and B-cell lymphoma 2 inhibitor (8.3%). In 2014-2017, the proportion of patients receiving sequential targeted therapy in the first 2 LOTs was 11.2% (80.2% was BTKi→BTKi); in 2018-2021, this proportion was 34.3% (66.4% was BTKi→BTKi). Over time, there was a substantial increase in targeted therapy use in 1 L and sequential targeted therapy, particularly with BTKi→BTKi. Future studies should assess clinical outcomes to determine optimal sequences for CLL/SLL and reasons for restarting BTKi.

Real-world analysis of adverse event rates after initiation of ibrutinib among Medicare beneficiaries with chronic lymphocytic leukemia.

BACKGROUND: The first-generation BTK inhibitor ibrutinib is a standard-of-care therapy in the treatment of chronic lymphocytic leukemia (CLL) despite potential side effects that often lead to discontinuation. METHODS: This study used 2013-2019 claims data to describe the incidence rate of adverse events (AEs) among elderly Medicare beneficiaries newly initiating ibrutinib for CLL. RESULTS: The final sample contained 11,870 Medicare beneficiaries with CLL (mean age 77.2) newly initiating ibrutinib, of whom 65.2% discontinued over mean follow-up of 2.3 years. The overall incidence rate of AEs was 62.5 per 1000 patient-months for all discontinuers and 32.9 per 1000 patient-months for non-discontinuers. Discontinuers had a higher incidence rate of AEs per 1000 patient-months compared with non-discontinuers for all AEs examined, including infection (22.8 vs. 14.5), atrial fibrillation (15.1 vs. 7.0), anemia (21.9 vs. 14.5), and arthralgia/myalgia (19.5 vs. 13.6). CONCLUSION: In this first real-world study of a national sample of elderly US patients treated with ibrutinib, we found a clear unmet need for improved management of ibrutinib-related AEs and/or new treatments to improve real-world outcomes in patients with CLL.

Treatment Patterns, Healthcare Resource Utilization, and Costs of Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in the US.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia among US adults and has experienced a rapidly evolving treatment landscape; yet current data on treatment patterns in clinical practice and economic burden are limited. This study aimed to provide an up-to-date description of real-world characteristics, treatments, and costs of patients with CLL or small lymphocytic lymphoma (SLL). MATERIALS AND METHODS: Using retrospective data from the Optum Clinformatics DataMart database (January 2013 to December 2021), adults with diagnosis codes for CLL/SLL on two different dates were selected. An adapted algorithm identified lines of therapy (LOT). Treatment patterns were stratified by the index year pre- and post-2018. Healthcare resource utilization and costs were evaluated per patient-years. RESULTS: A total of 18 418 patients with CLL/SLL were identified, 5226 patients (28%) were treated with ≥1 LOT and 1728 (9%) with ≥2 LOT. Among patients diagnosed with CLL in 2014-2017 and ≥1 LOT (N = 2585), 42% used targeted therapy and 30% used chemoimmunotherapy in first line (1L). The corresponding proportions of patients diagnosed with CLL in 2018-2021 (N = 2641) were 54% and 16%, respectively. Total costs were numerically 3.5 times higher and 4.9 times higher compared with baseline costs among patients treated with 1L+ and 3L+, respectively. CONCLUSION: This study documented the real-world change in CLL treatment landscape and the substantial economic burden of patients with CLL/SLL. Specifically, targeted therapies were increasingly used as 1L treatments and they were part of more than half of 1L regimens in recent years (2018-2021).

Ibrutinib discontinuation and associated factors in a real-world national sample of elderly Medicare beneficiaries with chronic lymphocytic leukemia.

Prior studies evaluating ibrutinib discontinuation are limited to clinical trials and selected medical centers and hence may not reflect real-world practice. This study used Medicare claims (2013-2019) to examine ibrutinib discontinuation and associated factors among elderly patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Over a median follow-up of 2.1 years, two-thirds (65.2%) of the 11,870 new ibrutinib initiators were discontinued, with half (45.1%) of patients discontinuing within 12 months of initiation. Factors such as advanced age, lack of Part D low-income subsidy, evidence of prior CLL/SLL treatment, and cardiovascular comorbidities (e.g. atrial fibrillation) were associated with higher risk of discontinuation. Over a median of 1.2 years from discontinuation, 40% of discontinuers initiated another CLL/SLL treatment after ibrutinib discontinuation; 25% of patients restarted ibrutinib treatment at some point over follow-up. Our findings point to a large unmet need with the widely used BTKi ibrutinib and underscore the importance of ongoing development of efficacious and well-tolerated CLL/SLL therapies.

Cost-effectiveness of varenicline compared with nicotine patches for smoking cessation--results from four European countries.

BACKGROUND: The aim of this study was to evaluate and compare the cost-effectiveness of varenicline with nicotine replacement therapy (NRT) for smoking cessation in four European countries (Belgium, France, Sweden and the UK). METHODS: Markov simulations, using the Benefits of Smoking Cessation on Outcomes (BENESCO) model, were performed. We simulated the incidence of four smoking-related morbidities: lung cancer, chronic obstructive pulmonary disease, coronary heart disease and stroke. The model computes quality-adjusted life-years gained and incremental cost-effectiveness ratios. Incremental cost-utility ratios were calculated, adopting a lifetime perspective. Efficacy data were obtained from a randomized open-label trial: Week 52 continuous abstinence rates were 26.1% for varenicline and 20.3% for NRT. RESULTS: The analyses imply that for countries analysed, smoking cessation using varenicline versus NRT was associated with reduced smoking-related morbidity and mortality. The number of morbidities avoided, per 1000 smokers attempting to quit, ranged from 9.7 in Belgium to 6.5 in the UK. The number of quality-adjusted life-years gained, per 1000 smokers, was 23 (Belgium); 19.5 (France); 29.9 (Sweden); and 23.7 (UK). In all base-case simulations (except France), varenicline dominated (more effective and cost saving) NRT regarding costs per quality-adjusted life-year gained; for France the incremental cost-effectiveness ratio was 2803. CONCLUSION: This cost-effectiveness analysis demonstrated that since varenicline treatment was more effective, the result was increased healthcare cost savings in Belgium, Sweden and the UK. Our results suggest that funding varenicline as a smoking cessation aid is justifiable from a healthcare resource allocation perspective.