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.

Evaluating population-level outcomes in Chronic Lymphocytic leukemia in the era of novel therapies using the SEER registry.

In the last decade, novel agents such as BTK and BCL-2 inhibitors have revolutionized treatment of CLL/SLL, with clinical trials showing improved overall survival compared to chemotherapeutic agents. However, studies examining whether they have improved overall survival at the population level are lacking. We evaluated this by conducting a retrospective analysis of CLL/SLL patients registered in the National Cancer Institute's surveillance epidemiology and end results (SEER) database, analyzing overall survival (OS) in periods pre- and post-availability of novel agents, along with demographic information. Our results showed that median OS significantly improved over time [7.8 years (2000-2005), 9.1 years (2006-2013), and not reached (2014-2018) (p < 0.001)]. Compared to diagnosis in 2014-2018, diagnosis in earlier periods was associated with higher mortality risk (2000-2005-HR 1.32, 95 % CI 1.28-1.37, p < 0.001: 2006-2013-HR 1.09, 95 % CI 1.06-1.13, p < 0.001). Lower mortality risk was seen in patients age < 85 years whereas median household income of <$75000 was associated with higher mortality. Our study provides real-world data suggesting a possible multifactorial contribution to improvement in survival, including availability of novel agents, better monitoring, and supportive care. They also show discrepancies in overall survival for CLL/SLL patients due to socioeconomic status and demographic factors.

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.

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).

Assessment of second primary malignancies among treated and untreated patients with chronic lymphocytic leukemia using real-world data from the USA.

Aim: Improved management of chronic lymphocytic leukemia (CLL) has resulted in a growing population of CLL survivors; these patients have a higher risk of developing second primary malignancies (SPMs) versus the general population. This retrospective cohort study aims to assess the timing, frequency, incidence and types of SPMs in treated and untreated patients with CLL in the USA, using the Surveillance, Epidemiology, and End Results (SEER) Medicare database, which links a nationally representative cancer registry with Medicare claims data. Patients & methods: Patients aged ≥66 years with newly diagnosed CLL between 1 January 2010 and 31 December 2016, who were enrolled in Parts A and B of Medicare for ≥12 months pre-diagnosis of CLL were selected from the database. Patients were assessed for ≥36 months until the end of continuous enrollment in Medicare Parts A, B and D, a switch to a health maintenance organization, death, or end of the study period (December 2019). Results: Of 3053 patients included in the analyses, 620 (20.3%) were treated and 2433 (79.7%) were untreated within 36 months of diagnosis. Overall, 638 (20.9%) patients developed a SPM, 26.8% of patients in the treated cohort and 19.4% of patients in the untreated cohort. The most common SPMs for both cohorts were squamous cell carcinoma and acute myeloid leukemia. Among the 166 treated patients who developed a SPM, a greater proportion developed their first SPM after treatment initiation versus those who developed their first SPM prior to treatment initiation (p < 0.001). A significantly lower percentage of patients who received targeted therapy developed a SPM (p < 0.05) versus patients treated with anti-CD20 + chemotherapy. Conclusion: Findings indicate that treatment type and timing can affect SPM development in patients with CLL. Combined with previous findings, this can help inform best practices in monitoring for SPM in patients with CLL.

Prognosis of older adults with chronic lymphocytic leukemia: A Surveillance, Epidemiology, and End Results-Medicare cohort study.

INTRODUCTION: While prognosis for patients with chronic lymphocytic leukemia (CLL) has improved over time in younger adults, only modest improvements have occurred in older adults. We conducted a descriptive study of prognosis in older adults with CLL. MATERIALS AND METHODS: We used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database from 2003 to 2016. We identified older adults (≥66 years) diagnosed with primary CLL between 2004 and 2015 (Overall Cohort). A subset who initiated CLL-directed therapy during the year following diagnosis was also identified (Treated Cohort). Both cohorts were matched to Medicare beneficiaries without cancer based on age, sex, and region. For each year from 2004 to 2013, three-year survival for patients with CLL and non-cancer comparators was described using Kaplan-Meier analysis. Inverse probability weighted Cox regression models were used to compare survival in the CLL and non-cancer comparator cohorts, accounting for demographic information and comorbidity and frailty indices. Among older adults with CLL, ten-year cause-specific cumulative mortality was estimated using Aalen-Johansen estimators that accounted for competing risks. Predictors of cause-specific mortality, including comorbidity and frailty burden, were assessed using sub-distribution hazards models. RESULTS: In the Overall Cohort, three-year survival increased non-monotonically from 71.4% in 2004 to 73.4% in 2013, with a peak of 74.4% in 2011, and was lower than survival in non-cancer comparators (78.3% in 2004 to 83.2% in 2013). In the Treated Cohort, three-year survival was 56.3% in 2004 and 56.5% in 2013, with a peak of 64.2% in 2011. Cox models suggested that survival in the Treated Cohort was approaching survival in non-cancer comparators after 2011 (hazard ratio = 1.04, 95% confidence interval, 0.93-1.17). Ten-year cumulative mortality was 68.6% in the Overall Cohort and 81.7% in the Treated Cohort, with most deaths attributed to non-CLL causes. In the sub-distribution hazards models, age, year of diagnosis, frailty, and comorbidities were all associated with prognosis. DISCUSSION: Prognosis in older adults has been stable over time and most patients with CLL die from non-CLL causes. CLL-directed treatment decision-making in older adults should consider age-related factors, such as comorbidity and frailty.

Elevated expression of interleukin 16 in chronic lymphocytic leukemia is associated with disease burden and abnormal immune microenvironment.

Interleukin-16 (IL-16) is a novel biomarker that has been implicated in many cancers as well as inflammatory diseases. In this study, we examined plasma levels of 30 cytokines and chemokines in chronic lymphocytic leukemia (CLL) and monoclonal B cell lymphocytosis (MBL) patients, and examined their association with disease stage, CLL biomarkers and T cell subsets. Interleukin 16 (IL-16) was identified as a relatively uncharacterized cytokine significantly elevated in CLL patients compared to healthy controls and MBL patients. Plasma levels of IL-16 were significantly elevated by Rai stage 0, increased by Rai stage 3-4, correlated strongly with lymphocyte count and were decreased after Ibrutinib treatment. CLL cells expressed IL-16 mRNA and spontaneously secreted IL-16 in vitro. CLL cells express IL-16 mRNA at significantly higher levels in lymphoid tissues than blood, and we observed that IL-16 release was increased in co-cultures of CLL and autologous CD4 + T cells. Elevated plasma IL-16 levels were associated with abnormalities in the immune microenvironment including multiple inflammatory cytokines and chemokines and expansion of type 1 follicular helper T cells. Taken together, our results identify IL-16 as a novel biomarker in CLL with potential functional roles in cellular interactions between CLL cells and T cells.

Systematic Literature Review of Economic Evaluations of Treatment Alternatives in Chronic Lymphocytic Leukemia.

BACKGROUND: Economic evaluations are widely used to predict the economic impact of new treatment alternatives. Comprehensive economic reviews in the field of chronic lymphocytic leukemia (CLL) are warranted to supplement the existing analyses focused on specific therapeutic areas. METHODS: A systematic literature review was conducted based on literature searches in Medline and EMBASE to summarize the published health economics models related to all types of CLL therapies. Narrative synthesis of relevant studies was performed focusing on compared treatments, patient populations, modelling approaches and key findings. RESULTS: We included 29 studies, the majority of which were published between 2016 and 2018, when data from large clinical trials in CLL became available. Treatment regimens were compared in 25 cases, while the remaining four studies considered treatment strategies with more complex patient pathways. Based on the review results, Markov modelling with a simple structure of three health states (progression-free, progressed, death) can be considered as the traditional basis to simulate cost effectiveness. However, more recent studies added further complexity, including additional health states for different therapies (e.g. best supportive care or stem cell transplantation), for progression-free state (e.g. by differentiating between with or without treatment), or for response status (i.e. partial response and complete response). CONCLUSIONS: As personalized medicine is increasingly gaining recognition, we expect that future economic evaluations will also incorporate new solutions, which are necessary to capture a larger number of genetic and molecular markers and more complex patient pathways with individual patient-level allocation of treatment options and thus economic assessments.

Dynamic Bayesian networks for prediction of health status and treatment effect in patients with chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is the most common blood cancer in adults. The course of CLL and patients' response to treatment are varied. This variability makes it difficult to select the most appropriate treatment regimen and predict the progression of the disease. This work was aimed at developing and validating dynamic Bayesian networks (DBNs) to predict changes of the health status of patients with CLL and progression of the disease over time. Two DBNs were developed and implemented i.e. Health Status Network (HSN) and Treatment Effect Network (TEN). Based on the literature data and expert knowledge we identified relationships linking the most important factors influencing the health status and treatment effects in patients with CLL. The developed networks, and in particular TEN, were able to predict probability of survival in patients with CLL, which was in line with the survival data collected in large medical registries. The networks can be used to personalize the predictions, taking into account a priori knowledge concerning a particular patient with CLL. The proposed approach can serve as a basis for the development of artificial intelligence systems that facilitate the choice of treatment that maximizes the chances of survival in patients with CLL.

Prognostic value of high-sensitivity measurable residual disease assessment after front-line chemoimmunotherapy in chronic lymphocytic leukemia.

Measurable residual disease (MRD) status is widely adopted in clinical trials in patients with chronic lymphocytic leukemia (CLL). Findings from FILO group trials (CLL2007FMP, CLL2007SA, CLL2010FMP) enabled investigation of the prognostic value of high-sensitivity (0.7 × 10-5) MRD assessment using flow cytometry, in blood (N = 401) and bone marrow (N = 339), after fludarabine, cyclophosphamide, and rituximab (FCR)-based chemoimmunotherapy in a homogeneous population with long follow-up (median 49.5 months). Addition of low-level positive MRD < 0.01% to MRD ≥ 0.01% increased the proportion of cases with positive MRD in blood by 39% and in bone marrow by 27%. Compared to low-level positive MRD < 0.01%, undetectable MRD was associated with significantly longer progression-free survival (PFS) when using blood (72.2 versus 42.7 months; hazard ratio 0.40, p = 0.0003), but not when using bone marrow. Upon further stratification, positive blood MRD at any level, compared to undetectable blood MRD, was associated with shorter PFS irrespective of clinical complete or partial remission, and a lower 5-year PFS rate irrespective of IGHV-mutated or -unmutated status (all p < 0.05). In conclusion, high-sensitivity (0.0007%) MRD assessment in blood yielded additional prognostic information beyond the current standard sensitivity (0.01%). Our approach provides a model for future determination of the optimal MRD investigative strategy for any regimen.

Healthcare resource utilization and costs associated with first-line ibrutinib compared to chemoimmunotherapy treatment among Medicare beneficiaries with chronic lymphocytic leukemia.

OBJECTIVE: This retrospective observational study aimed to compare healthcare resource utilization and costs of Medicare beneficiaries with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who received ibrutinib versus chemoimmunotherapy (CIT) in first line (1 L). METHODS: Fee-for-service (FFS) and Medicare Advantage (MA) claims data were used to identify adults with a CLL/SLL diagnosis initiating 1 L ibrutinib single agent or CIT between 4 March 2016 and 30 September 2017 (index date). HRU and costs (Medicare spending) were evaluated during 1 L Oncology Care Model (1 L OCM) episodes (the first six months post-index) and over the observed 1 L duration. Patients' baseline characteristics were balanced using inverse probability of treatment weighting. Mean monthly cost differences (MMCDs) obtained from ordinary least square regressions were used to compare costs between ibrutinib and CIT cohorts. RESULTS: In the Medicare FFS dataset (ibrutinib: n = 2014; CIT: n = 2050), ibrutinib patients incurred significantly higher monthly pharmacy costs (1 L OCM: MMCD = $4878, p < .0001; 1 L duration: MMCD= $4892, p < .0001) that were fully offset by lower monthly medical costs (1 L OCM: MMCD= -$8289, p < .0001; 1 L duration: MMCD=-$5888, p < .0001), yielding a monthly total healthcare cost reduction (1 L OCM: MMCD=-$3411, p < .0001; 1 L duration: MMCD=-$996, p < .0001) relative to CIT patients. In the MA dataset (ibrutinib: n = 293; CIT: n = 303), ibrutinib was also associated with a monthly total healthcare cost reduction (1 L OCM: MMCD=-$10,459; 1 L duration: MMCD=-$5492). CONCLUSIONS: In Medicare patients with CLL/SLL, 1 L ibrutinib single agent was associated with total monthly cost savings relative to 1 L CIT, driven by lower monthly medical costs that fully offset higher monthly pharmacy costs.

The evolving use of minimal residual disease (MRD) assessment in chronic lymphocytic leukemia.

The treatment of chronic lymphocytic leukemia (CLL) has changed remarkably throughout the past decade, with patients achieving deeper and more durable responses. Importantly, this clinical activity has been found to translate to prolonged survival. With some treatments, these responses are now allowing patients to stop therapy after 1 or 2 years, a concept referred to as "fixed duration." However, not all patients experience these outcomes. How to determine which patients can safely stop treatment remains unclear. Minimal residual disease (MRD) is emerging as a prognostic biomarker. In CLL, undetectable MRD has been shown to correlate with prolonged progression-free survival and, in some cases, overall survival. The incorporation of MRD status into clinical decision-making is not yet widely done, primarily based on the lack of prospective clinical trial data. As the endpoint of MRD status becomes more common in clinical trials of CLL, the role in the clinical setting will become more clear. Furthermore, prognostic models will help to determine the utility of MRD as a surrogate endpoint in clinical studies. This monograph examines clinical trial data regarding the role of MRD in CLL, and provides recommendations on how to incorporate MRD assessment into clinical management.

Comparison of Time to Next Treatment, Health Care Resource Utilization, and Costs in Patients with Chronic Lymphocytic Leukemia Initiated on Front-line Ibrutinib or Chemoimmunotherapy.

BACKGROUND: Studies assessing ibrutinib's economic burden versus chemoimmunotherapy (CIT) focused on pharmacy costs but not medical costs. This study compared time to next treatment (TTNT), health care resource utilization (HRU), and total direct costs among patients with chronic lymphocytic leukemia (CLL) initiating front-line ibrutinib single agent (Ibr) or CIT. MATERIALS AND METHODS: Optum Clinformatics Extended DataMart De-Identified Databases were used to identify adults with ≥ 2 claims with a CLL diagnosis initiating front-line Ibr or CIT from February 12, 2014 to June 30, 2017. Inverse probability of treatment weighting was used to control for potential differences in baseline characteristics between the Ibr and CIT cohorts. Two periods were considered: entire front-line therapy (until initiation of second-line therapy) and first 6 months of front-line therapy. Comparisons with a subgroup of CIT patients initiating bendamustine/rituximab (BR) were also conducted. RESULTS: TTNT was significantly longer for Ibr (N = 322) relative to CIT (N = 839; hazard ratio, 0.54; P = .0163; Kaplan-Meier rates [24 months]: Ibr = 88.6%, CIT = 75.9%) and the subset of CIT patients treated with BR (N = 455; hazard ratio, 0.54; P = .0208; Kaplan-Meier rates [24 months]: Ibr = 89.0%, BR = 79.0%). During the entire front-line therapy, Ibr patients had significantly fewer monthly days with outpatient visits (rate ratio = 0.75; P = .0200). Ibrutinib's higher pharmacy costs (mean monthly cost difference [MMCD] = $6,849; P < .0001) were offset by lower medical costs (MMCD = -$10,615; P < .0001), yielding net savings (MMCD = -$3,766; P < .0001) versus CIT. Ibr was associated with net savings (MMCD = -$5,569; P < .0001) versus BR. Cost savings and reductions in HRU were more pronounced during the first 6 months of front-line therapy. CONCLUSION: During front-line CLL treatment, Ibr was associated with longer TTNT, fewer monthly days with outpatient visits, and net monthly total cost reduction versus CIT and BR.

Treatment patterns, adverse events, and economic burden in a privately insured population of patients with chronic lymphocytic leukemia in the United States.

INTRODUCTION: Contemporary data describing treatment patterns, adverse events (AEs), and outcomes in patients with chronic lymphocytic leukemia (CLL) in clinical practice are lacking. We conducted a retrospective cohort study and assessed treatment patterns, AEs, health-care resource use (HCRU), and costs in patients with diagnosis of CLL. METHODS: Using a nationally representative population of privately insured patients in the US, adult patients with CLL diagnosis (July 2012-June 2015) were selected if they had continuous health plan enrollment for ≥12 months before the first CLL diagnosis without any evidence of any CLL-directed treatment. Treatment patterns up to four lines of therapy (LOT) and occurrence of AEs during CLL therapies were assessed. Mean per-patient monthly HCRU and costs were assessed overall and by number of unique AEs. RESULTS: Of all patients meeting the selection criteria (n = 7,639; median age, 66 years), 18% (n = 1,379) received a systemic therapy during study follow-up. Of these, bendamustine/rituximab (BR) was the most common first observed regimen (28.1%), while ibrutinib was the most common therapy in the second (20.8%) and third (25.5%) observed regimens. The mean monthly all-cause and CLL-related costs, among patients treated with a systemic therapy, were $7,943 (SD = $15,757) and $5,185 (SD = $9,935), respectively. Mean monthly all-cause costs increased by the number of AEs (from $905 [SD = $1,865] among those with no AEs to $6,032 [SD = $13,290] among those with ≥6 AEs). CONCLUSIONS: Chemoimmunotherapy, particularly BR, was the most common first observed therapy for CLL, whereas ibrutinib was most preferred in the second and third observed lines of therapy during the study period. Findings demonstrate that the economic burden of AEs in CLL is substantial.

Comparative assessment of prognostic models in chronic lymphocytic leukemia: evaluation in Indian cohort.

Prognostic indices combining several clinical and laboratory parameters have been proposed for prognostication in chronic lymphocytic leukemia (CLL). Recently, international consortium on CLL proposed an international prognostic index (CLL-IPI) integrating clinical, molecular, and genetic parameters. The present study was designed to evaluate the reproducibility of CLL-IPI in Indian CLL cohort. The prognostic ability of CLL-IPI in terms of overall survival (OS) and time to first treatment (TTFT) was investigated in treatment-naive CLL patients and also compared with other existing prognostic scores. For assigning scores, clinical and laboratory details were obtained from medical records, and IGHV gene mutation status, ß2-microglobulin levels, and copy number variations were determined using c-DNA, ELISA, and multiplex ligation-dependent probe amplification (MLPA), respectively. The scores were generated as per the weighted grades assigned to each variable involved in score categorization. The predictive value of prognostic models was assessed and compared using Harrell's C-index and Akaike's information criterion (AIC). Stratification of patients according to CLL-IPI yielded significant differences in terms of OS and TTFT (p < 0.001). Comparative assessment of scores for OS suggested better performance of CLL-IPI (C = 0.64, AIC = 740) followed by Barcelona-Brno (C = 0.61, AIC = 754) and MDACC score (C = 0.59, AIC = 759). Comparison of predictive value of prognostic scores for TTFT illustrated better performance of CLL-IPI (C = 0.72, AIC = 726) followed by Barcelona-Brno (C = 0.68, AIC = 743), modified GCLLSG (C = 0.66, AIC = 744), and O-CLL1 index (C = 0.55, AIC = 773). The results suggest better performance of CLL-IPI in terms of both OS and TTFT as compared to other available scores in our cohort.

[Evaluation of management disparity in patients with chronic lymphocytic leukemia in France]. / Évaluation de la disparité de prise en charge des patients avec une leucémie lymphoïde chronique en France.

Environmental factors have an impact on the effectiveness of treatments for chronic lymphocytic leukemia: vulnerability, organization of the supply of care and proximity of the patient to health professionals. The disparity of care was assessed; vulnerability by the European index of deprivation, the provision of care by values of localized potential accessibility to general practitioners, nurses and pharmacists and hospital supply by the density of hematologists and time access to the center. The data, extracted from the public databases for each grouped island for statistical information, were cross-referenced to apply a principal component analysis and group them into 4 clusters. Cluster 1 has an average EDI, easy access to city professionals, remote access to the referral center, and a good density of hematologists. Cluster 2 has low EDI, satisfactory access to professionals, satisfactory proximity to the referral center and average density of hematologists. Cluster 3 has good EDI, access to professionals is difficult, access to the reference center is long, and the density of hematologists remains average. Cluster 4 has a good EDI, with access to professionals easier than in Cluster 3 but still difficult. The access time to the reference center is better than that of cluster 3 but remains elongated, the density of hematologists remaining average. Mapping is a tool for hospitals and institutions to evaluate care and compare it to other territories.

Economic burden of treatment failure in chronic lymphocytic leukemia patients.

OBJECTIVE: This study assessed healthcare costs of first-line treatment failure (TF) in patients with chronic lymphocytic leukemia (CLL), a subtype of non-Hodgkin's lymphoma. METHODS: Pre-diagnosis treatment-naïve adults with ≥2 CLL diagnoses initiated on an antineoplastic agent (index date) after their first CLL diagnosis with ≥12 and ≥6 months of continuous observation pre- and post-index, respectively, were selected from the Truven Health MarketScan Research Databases. Patients had no solid malignancies in the pre-index period nor selected blood malignancies at any time. Initial therapy included antineoplastic agents initiated in the first 30 days post-index. TF occurred at the earliest of: initiation of a new antineoplastic agent, treatment resumption following a ≥3 month break, non-chemotherapy intervention (stem cell transplant or radiotherapy), hospice care or hospital mortality. The cost of TF was evaluated as the healthcare cost difference between patients with and without first-line TF using ordinary least square regressions adjusted for baseline characteristics. Non-parametric bootstrap was used to evaluate statistical significance. RESULTS: Among 2226 patients identified (mean age: 68 years; female: 41%), 46% experienced first-line TF. The average TF cost was $3011 per patient per month (p < .001). When stratifying patients by event indicating TF and by most common therapies, non-chemotherapy intervention ($7582 per patient per month; p < .0001) and fludarabine/cyclophosphamide/rituximab ($4758; p < .001) were associated with the highest TF cost, respectively. CONCLUSIONS: The cost of first-line TF is high and varies across first-line therapies. This should be considered when selecting the initial therapy in these patients.

iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL.

The previous edition of the consensus guidelines of the International Workshop on Chronic Lymphocytic Leukemia (iwCLL), published in 2008, has found broad acceptance by physicians and investigators caring for patients with CLL. Recent advances including the discovery of the genomic landscape of the disease, the development of genetic tests with prognostic relevance, and the detection of minimal residual disease (MRD), coupled with the increased availability of novel targeted agents with impressive efficacy, prompted an international panel to provide updated evidence- and expert opinion-based recommendations. These recommendations include a revised version of the iwCLL response criteria, an update on the use of MRD status for clinical evaluation, and recommendations regarding the assessment and prophylaxis of viral diseases during management of CLL.