Costs and health care resource utilization among Medicare beneficiaries diagnosed with chronic lymphocytic leukemia.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common type of leukemia. However, published studies of CLL have either only focused on costs among individuals diagnosed with CLL without a non-CLL comparator group or focused on costs associated with specific CLL treatments. An examination of utilization and costs across different care settings provides a holistic view of utilization associated with CLL. OBJECTIVE: To quantify the health care costs and resource utilization types attributable to CLL among Medicare beneficiaries and identify predictors associated with each of the economic outcomes among beneficiaries diagnosed with CLL. METHODS: This retrospective study used a random 20% sample of the Medicare Chronic Conditions Data Warehouse (CCW) database covering the 2017-2019 period. The study population consisted of individuals with and without CLL. The CLL cohort and non-CLL cohort were matched using a 1:5 hard match based on baseline categorical variables. We characterized economic outcomes over 360 days across cost categories and places of services. We estimated average marginal effects using multivariable generalized linear regression models of total costs and across type of services. Total cost was compared between CLL and non-CLL cohorts using the matched sample. We used generalized linear models appropriate for the count or binary outcome to identify factors associated with various categories of health care resource utilization, such as inpatient admissions, emergency department (ED) visits, and oncologist/hematologist visits. RESULTS: A total of 2,736 beneficiaries in the CLL cohort and 13,571 beneficiaries in the non-CLL matched cohort were identified. Compared with the non-CLL cohort, the annual cost for the CLL cohort was higher (CLL vs non-CLL, mean [SD]: $22,781 [$37,592] vs $13,901 [$24,725]), mainly driven by health care provider costs ($6,535 vs $3,915) and Part D prescription drug costs ($5,916 vs $2,556). The main categories of health care resource utilization were physician evaluation/management visits, oncologist/hematologist visits, and laboratory services. Compared with beneficiaries aged 65-74 years, beneficiaries aged 85 years or older had lower use and cost in maintenance services (ie, oncologist visits, hospital outpatient costs, and prescription drug cost) but higher use and cost in acute services (ie, ED). Compared with residency in a metropolitan area, living in a nonmetropolitan area was associated with fewer physician visits but higher ED visits and hospitalizations. CONCLUSIONS: The cooccurrence of lower utilization of routine care services, along with higher utilization of acute care services among some individuals, has implications for patient burden and warrants further study.

Disparity in treatment patterns among Medicare beneficiaries diagnosed with chronic lymphocytic leukemia: an analysis of patient and contextual factors.

This study characterizes the patterns and timing of CLL treatment and, to our knowledge, is the first to identify social vulnerability factors associated with CLL treatment receipt in the Medicare population. A total of 3508 Medicare beneficiaries diagnosed with CLL from 2017 to 2019 were identified. We reported the proportion of individuals who received CLL treatment and the time until the first CLL treatment receipt after the first observed claim with a CLL diagnosis. Logistic regression and time-to-event models provided adjusted odds ratios and hazard ratios associated with baseline individual-level and county-level factors. Sixteen percent of individuals received CLL treatment, and the median follow-up time was 540 d. The median time to receipt of CLL treatment was 61 d. Older age and residence in a county ranked high in social vulnerability (as defined by minority status and language) were negatively associated with treatment receipt and time to treatment receipt.

Health-related quality-of-life in treatment-naive CLL/SLL patients treated with zanubrutinib versus bendamustine plus rituximab.

OBJECTIVE: Zanubrutinib is a highly selective, next-generation Bruton's tyrosine kinase inhibitor. In the phase 3 SEQUOIA trial (NCT03336333), treatment with zanubrutinib resulted in significantly improved progression-free survival compared to bendamustine plus rituximab (BR) in adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) without del(17p). The current analysis compared the effects of zanubrutinib versus BR on patients' health-related quality-of-life (HRQoL). METHODS: In the SEQUOIA trial, patient-reported outcomes (PROs) were assessed at baseline and every 12 weeks (3 cycles) using the EORTC QLQ-C30 and EQ-5D-5L. Descriptive analyses were performed on all the questionnaires' scales and a mixed model for repeated measures was performed using the key QLQ-C30 endpoints of global health status/QoL (GHS/QoL), physical and role functioning, and symptoms of fatigue, pain, diarrhea, and nausea/vomiting at weeks 12 and 24. RESULTS: Compared with BR-treated patients, those in the zanubrutinib arm experienced greater improvements in HRQoL outcomes at both weeks 12 and 24. By week 24, mean change differences (95% confidence interval) between the arms were significant for GHS/QoL (4.9 [0.9, 9.0]), physical functioning (3.8 [0.8, 6.7]), diarrhea (-6.2 [-10.0, -2.5]), fatigue (-4.5 [-8.9, -0.1]), and nausea/vomiting (-4.5 [-8.9, -0.1]); role functioning (4.8 [-0.2, 9.7]) was marginally better in the zanubrutinib arm and there were no differences in pain symptoms (-0.4 [-4.3, 5.1]) between the arms. CONCLUSIONS: During the first 24 weeks of treatment, zanubrutinib was associated with better HRQoL outcomes in patients with treatment-naive CLL/SLL without del(17p) compared to BR. TRIAL REGISTRATION: The SEQUOIA trial is registered on clinicaltrials.gov as SEQUOIA trial (NCT03336333).

Health-related quality of life outcomes associated with zanubrutinib versus ibrutinib monotherapy in patients with relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma: results from the ALPINE Trial.

OBJECTIVE: The purpose of this analysis was to assess health-related quality of life (HRQoL) in patients treated with zanubrutinib and ibrutinib in the ALPINE trial (NCT03734016). METHODS: HRQoL was measured by the EORTC QLQ-C30 and EQ-5D-5L at baseline, cycle 1, and every third cycle until the end of treatment. Key patient-reported outcome (PRO) endpoints included global health status (GHS), physical and role functioning, as well as symptoms of fatigue, pain, diarrhea, and nausea/vomiting. A mixed model repeated-measure analysis using key PRO endpoints at key clinical cycles (cycles 7 and 13) was performed. RESULTS: 652 patients were randomized to receive zanubrutinib (n = 327) or ibrutinib (n = 325). By cycle 7, GHS scores improved with zanubrutinib versus ibrutinib, and in cycle 13, GHS scores remained higher in the zanubrutinib arm. The zanubrutinib arm experienced clinically meaningful improvements in physical and role functioning, as well as pain and fatigue symptoms at both cycles. Patients in the zanubrutinib arm reported lower diarrhea scores. Nausea/vomiting scores maintained in both arms. EQ-VAS scores showed greater improvement from baseline at both cycle 7 (7.92 versus 3.44) and cycle 13 (7.75 versus 3.92) of treatment with zanubrutinib compared to ibrutinib, respectively. CONCLUSIONS: Patients with R/R CLL/SLL treated with zanubrutinib demonstrated improvement versus ibrutinib in the GHS scale at cycle 7. Other endpoints continued to improve, suggesting treatment with zanubrutinib positively affected HRQoL over time. Given the generally good HRQoL at baseline in both arms, the differences between the arms were not significant.

Impact of atrial fibrillation in onco-hematological patients in Europe: a targeted literature review.

INTRODUCTION: Atrial fibrillation (AF) is a common complication in cancer patients, and the increased risk associated with certain therapies poses a major challenge. The objective was to determine the clinical and economic burden of AF in onco-hematological patients in Europe. AREAS COVERED: A targeted literature review was completed for observational, retrospective and case studies, and reviews on AF in onco-hematology published between January 2010 and 2022 in PubMed, Science Direct, Medes and IBECS. The search was based on epidemiology, cost, health-related quality of life (HRQoL), disease burden and management, and patient journey. Thirty-one studies fulfilled eligibility criteria. Annual incidence of AF during treatment varies up to 25%, and increased with first-generation Bruton tyrosine kinase inhibitors (BTKi). Risk factors include age ≥65, prior AF or hypertension, hyperlipidemia and ibrutinib use. Complications are managed with anticoagulants and/or antiarrhythmics, and regular monitoring. When AF is no longer controllable, dose reduction or discontinuation is recommended. No data on costs, HRQoL and patient journey were identified. EXPERT OPINION: There is scarce and heterogeneous information on AF in onco-hematology in Europe. Available evidence reports a higher risk of AF associated with first-generation BTKi. Further studies are needed to understand the burden of AF in these patients.

A real-world study to assess the association of cardiovascular adverse events (CVAEs) with ibrutinib as first-line (1L) treatment for patients with chronic lymphocytic leukaemia (CLL) in the United States.

Ibrutinib, a Bruton's tyrosine kinase inhibitor, is often used as first-line (1L) treatment of chronic lymphocytic leukaemia (CLL); however, it is associated with an increased risk for cardiovascular adverse events (CVAEs). This real-world study adds to existing literature by simultaneously investigating the correlation between pre-existing CV risk factors and the relative cardiotoxicity of ibrutinib vs other therapies in CLL/small lymphocytic lymphoma (SLL). Using a real-world database, the risk of subsequent CVAEs (any CVAE, atrial fibrillation [AF], or hypertension) were compared among patients who received 1L ibrutinib monotherapy or another type of non-ibrutinib therapy, grouped as intensive (IT) or non-intensive therapy (NIT). Each patient's baseline CV risk was estimated using the Framingham risk score. Inverse probability treatment weighting was incorporated into a logistic regression model to reduce baseline imbalance. Results showed ibrutinib was significantly associated with higher risk of CVAEs regardless of baseline CV risk. Compared with IT, odds ratios of any CVAE, hypertension, or AF were 2.61, 3.66, and 3.02, respectively vs 1.88, 2.13, and 2.46, respectively, with NIT. Sensitivity analyses confirmed the findings were robust. These results suggest clinical caution should be taken when selecting ibrutinib for patients with CLL/SLL, especially in those with high baseline CV risk.

A clinical practice comparison of patients with chronic lymphocytic leukemia with and without deletion 17p receiving first-line treatment with ibrutinib.

Among patients with chronic lymphocytic leukemia (CLL) with deletion 17p (del[17p]), evidence from clinical trials for the effectiveness of single-agent ibrutinib as first-line therapy is limited. This retrospective analysis compared real-world clinical outcomes among patients with CLL, with and without del(17p), treated with first-line ibrutinib monotherapy. Overall survival, time to next treatment, time to treatment discontinuation, and reasons for ibrutinib discontinuation were evaluated. Using data from a real-world database, patients included were aged ≥18 years, had been diagnosed with CLL between January 1, 2011 and December 31, 2019, had undergone cytogenetic testing, and had received first-line ibrutinib monotherapy. A total of 1,069 patients were included in the analysis (62.7% male; median age 69 years); 23.8% (n=254) had del(17p). The median overall survival was significantly shorter in patients with del(17p) than in patients without (57.7 months vs. not reached; P=0.0006). Similar results were observed for median time to next treatment (49.4 months vs. not reached, P=0.0330). The median time to treatment discontinuation was non-significantly shorter in the group of patients with del(17p) (32.5 months vs. 42.9 months, P=0.3370). Results of an adjusted Cox proportional hazards model showed that the group with del(17p) was at significantly higher risk of death than was the group without del(17p) (hazard ratio=1.70, P=0.0031). Event rates for switching to new treatment and discontinuation were higher but not statistically significantly so. The most common reason for discontinuing ibrutinib treatment in both groups was toxicity, but discontinuation due to progression was significantly more frequent among patients with del(17p) (20% vs. 6%; P<0.0001). This study identifies an unmet need for more effective first-line therapeutic options in patients with CLL/small lymphocytic lymphoma and del(17p), despite the advent of ibrutinib.

Use of PD-1 and PD-L1 inhibitors after first-line therapy in esophageal cancer patients in the US.

INTRODUCTION: Esophageal cancer (EC) makes up 3.2% of all cancers but ranks sixth among cancer-related deaths worldwide. This real-world analysis determined the use of PD-1/PD-L1 (PD[L]1) inhibitors in EC patients after receiving first-line therapy. METHODS: Newly diagnosed EC patients initiating first-line treatment were identified in the IBM MarketScan administrative claims databases during the study period (1 May 2015 to 31 October 2020) using ICD-9/ICD-10 codes. Patients were assigned to either the chemotherapy only, radiation only, chemotherapy plus radiation (chemoradiation), or esophageal transhiatal/transthoracic surgery cohorts. RESULTS: 7276 EC patients started first-line therapy (chemotherapy only = 2502, radiation only = 3355, chemoradiation = 1180, surgery = 239). The average age at diagnosis was 62 years and 23% were female. The median time from start of first-line therapy to utilization of a PD(L)1 inhibitor was 259 days. Pembrolizumab (72%) was the most frequently used PD(L)1 inhibitor across the three cohorts, followed by nivolumab (25%). Furthermore, the number of patients receiving a PD(L)1 inhibitor increased each year with the majority (73%) of use occurring between 2018 and 2020. DISCUSSION: Findings from this real-world study suggest that PD(L)1 inhibitors are increasingly used after first-line therapies in EC, especially among patients initially receiving chemotherapy only. New immunological therapies such as PD(L)1 inhibitors hold great promise for patients with solid tumors. A clearer understanding of their real-world utilization is critical.