Economic modeling to evaluate the impact of chronic myeloid leukemia therapy management on the oncology care model in the US.

Objective: To develop an economic model to evaluate changes in healthcare costs driven by restricting usage of branded tyrosine kinase inhibitors (TKIs) through substitution with generic imatinib among chronic myeloid leukemia (CML) patients in a typical Oncology Care Model (OCM) practice, and examine the impact on Performance-Based Payment (PBP) eligibility. Methods: An Excel-based economic model of an OCM practice with 1,000 cancer patients during a 6-month episode of care was developed. Cancer types and proportions of patients treated in the practice were estimated from an OCM report. All-cause healthcare costs were obtained from published literature. It was assumed that if a practice restricts usage of branded TKIs for newly-diagnosed CML patients, 80% of the market share of branded imatinib and 50% of the market shares of 2nd-gen TKIs would shift to generic imatinib. Among established TKI-treated patients, it was assumed that 80% of the market share of branded imatinib and no patients treated with 2nd-gen TKIs would shift to the generic. Results: Four CML patients were estimated for a 1,000-cancer patient OCM practice with a total baseline healthcare cost of $51,345,812 during a 6-month episode. If the practice restricts usage of branded TKIs, the shift from 2nd-gen TKIs to generic imatinib would reduce costs by $12,970, while shifting from branded to generic imatinib lowers costs by $25,250 during a 6-month episode. Minimum reductions of $3,013,832 in a one-sided risk model and $2,372,010 in a two-sided risk model are required for PBP eligibility; the shift from 2nd-gen TKIs to generic imatinib would account for 0.4% and 0.5% of the savings required for a PBP, respectively. Conclusions: This analysis indicates that the potential cost reduction associated with restricting branded TKI usage among CML patients in an OCM setting will represent only a small proportion of the cost reduction needed for PBP eligibility.

Impact of earlier versus later monitoring on disease progression and healthcare costs among patients with chronic myeloid leukemia in the United States.

We evaluated the impact of molecular monitoring earlier as compared to later in the course of chronic myeloid leukemia (CML) on disease progression and healthcare costs in the real-world setting in the US. Patients with a diagnosis of CML were identified from the MarketScan claims databases (1 January 2006 to 30 June 2016). Multivariable regression analyses were used to control for differences in patient cohorts with earlier versus later monitoring. Of the 2730 CML patients in the study population, 60% (n = 1633) received earlier monitoring and 40% (n = 1097) received later monitoring only. After adjusting for differences in patient characteristics, patients with earlier monitoring had a lower likelihood of CML progression during the follow-up period (odds ratio: 0.72, confidence interval: 0.53-0.96; p = .03) and lower total healthcare costs ($6794 versus $9782 per-patient-per-month, p < .001) than patients with later monitoring. Patients who are monitored earlier in the course of CML may have better outcomes and lower total costs of care.

Bone marrow core biopsy in 508 consecutive patients with chronic myeloid leukemia: Assessment of potential value.

BACKGROUND: The diagnosis of chronic myeloid leukemia (CML) is based on characteristic clinical and laboratory findings and the presence of BCR/ABL1 in the blood and/or bone marrow (BM). The utility of BM core biopsy in the workup of patients with CML has been questioned. METHODS: The potential added value of BM biopsy versus aspiration in the workup of a single-institution series of 508 patients with CML at their initial presentation was systematically assessed. BM biopsy was considered essential when it was needed to establish the disease phase, often because blast counts derived from aspirate smears were misleading because the biopsy specimen was more representative of the disease. BM biopsy was considered helpful if it was needed for other nonessential reasons. RESULTS: In 127 patients (25%), BM biopsy was either essential (109 patients) or helpful (18 patients). Patients with accelerated-phase (AP) or blast-phase (BP) disease often required a biopsy related to essential reasons. High-grade myelofibrosis (MF) was more frequent in patients with AP/BP disease than patients with chronic-phase disease (P = .0005), and the identification of BP disease required a BM biopsy assessment in 75% of the patients (P = .001). A follow-up BM evaluation more often yielded inadequate aspirates in patients with inadequate BM aspirates at the time of their initial diagnosis. CONCLUSIONS: BM core biopsy remains valuable in the workup of 25% of patients with CML because it facilitates identification of the disease phase or MF. The initial grade of MF is associated with the disease stage and outcome after therapy. BM biopsy is, therefore, indicated for patients with CML who have AP/BP disease or other findings suggestive of progressive disease.

Economic value of regular monitoring of response to treatment among US patients with chronic myeloid leukemia based on an economic model.

BACKGROUND: Regular molecular monitoring with reverse-transcription quantitative PCR (RT-qPCR) analysis of BCR-ABL1 transcripts is associated with reduced disease progression among patients with chronic myeloid leukemia (CML). Molecular monitoring assists in the timely detection of primary or secondary resistance to tyrosine kinase inhibitor (TKI) therapy and is a recommended practice by the National Comprehensive Cancer Network guidelines. An economic model was developed to estimate the potential impact of CML monitoring vs lack of monitoring on patient healthcare costs. METHODS: An Excel-based decision-analytic economic model was developed from a US payer perspective. The model was used to estimate the expected healthcare cost differences between regular molecular monitoring of CML patients and lack of monitoring. CML progression rates among patients with vs without monitoring, the annual cost of CML progression, the average number of monitoring tests per year, and the average cost per RT-qPCR monitoring test were incorporated into the model. Univariate and multivariable sensitivity analyses were conducted. RESULTS: Based on estimates in published literature, disease progression to the accelerated/blast phase occurs among 0.35% of patients with monitoring and 5.12% of patients without monitoring, and the annual cost of CML progression is $136,308 per patient year. The analysis found that total healthcare costs, including the costs associated with CML progression and RT-qPCR monitoring tests (three tests per year), were $1,142 for patients with monitoring and $6,982 for patients without monitoring (difference = $5,840). In a hypothetical cohort of 100 patients with CML, achieving a 100% monitoring rate was associated with a total cost-savings of $584,005 compared to a 0% monitoring rate. This cost-savings remained consistent under both univariate and multivariable sensitivity analyses. CONCLUSION: Regular CML monitoring was associated with improved outcomes among CML patients and, consequently, reduced healthcare costs.

Evaluation of healthcare resource utilization and incremental economic burden of patients with chronic myeloid leukemia after disease progression to blast phase.

AIMS: To evaluate healthcare resource utilization and economic burden of patients with chronic myeloid leukemia (CML) progression to the blast phase. METHODS: Patients (≥ 18 years) with ≥1 inpatient or ≥2 outpatient CML diagnoses were identified from the MarketScan Commercial and Medicare databases (January 1, 2007-June 30, 2015). CML patients were grouped into two study cohorts, those with evidence of disease progression to the blast phase and those without. Patients were required to have continuous medical and prescription coverage during a 12-month baseline period, in which demographics and clinical characteristics were evaluated. All-cause healthcare resource utilization and costs were evaluated during the baseline period, and a variable follow-up period, lasting ≥1 day and up to 1 year. Generalized linear models (GLM) were used to compare the incremental costs of CML patients with vs without progression. RESULTS: Of the overall study population, 587 (7%) experienced disease progression and 7,504 (93%) did not. On the index date, of patients with progression, ∼ 31% were treated with allogeneic hematopoietic cell transplant and 69% with chemotherapy. During the baseline period, mean total healthcare costs, including costs for hospitalizations and outpatient costs, were significantly greater for CML patients with progression as compared to those without progression ($143,778 vs $53,143, p < .001). During the follow-up, mean total healthcare costs, costs for hospitalizations, and outpatient medical service costs were substantially greater for patients with progression as compared to those without progression; however, costs for outpatient prescriptions were less for patients who progressed. When patient characteristics were controlled for, mean incremental 1-year cost for CML patients with vs without progression was $270,925 (confidence interval = $235,290-$311,958, p < .001). CONCLUSIONS: The healthcare burden, in terms of healthcare resource utilization and costs, of patients with CML progression is substantial. Healthcare providers and payers should consider various strategies to minimize the rate of CML progression.

Acute lymphoblastic leukemia in adolescents and young adults.

Acute lymphoblastic leukemia (ALL) in the adolescent and young adult (AYA) population is a difficult clinical problem. The AYA population, generally regarded as patients aged 15 to 39 years, currently draws a good deal of attention, particularly in the area of therapy selection. The current trend is to treat this group of patients with leukemia regimens based on pediatric protocols, and results comparing pediatric approaches versus adult approaches to treatment are maturing. Results are pending from a large US trial in which pediatric-based treatment is given to AYA patients with ALL. In tandem with these new clinical trials, researchers have reported disease features in the AYA group that may explain some of the differences in response to treatment observed in the AYA population compared with the pediatric population. In addition, unique social factors in this age group add to the complexity of ALL therapy in the AYA population. AYA patients are developing independence and separating from their parents. They tend to be noncompliant. Young adults suffer from a lack of health care insurance and poor access to clinical trials, and have specific concerns regarding toxicities, in particular fertility. Cancer 2017;123:2398-403. © 2017 American Cancer Society.

Myelodysplastic syndromes following therapy with hypomethylating agents (HMAs): development of acute erythroleukemia may not influence assessment of treatment response.

This study followed 28 patients with myelodysplastic syndromes (MDS) who showed a rise of bone marrow (BM) erythroids to ≥ 50% following three cycles (1-60) of hypomethylating agent (HMA) therapy. If BM blasts were calculated as a percentage of non-erythroids, 12 (42.9%) patients met the diagnostic criteria for acute erythroleukemia, erythroid/myeloid (AEL). However, none of the patients showed clonal cytogenetic evolution or new mutations. When compared to 47 de novo AEL patients, these 12 patients were less anemic and thrombocytopenic, had less complex karyotypes (p = 0.044) and showed a longer survival, either calculated from diagnosis (p < 0.001) or from the time of AEL (p = 0.005). These findings illustrate that ≥ 50% erythroids may appear in BM post-HMA therapy, likely a combination of reduction of BM granulocytes (p < 0.001) and promotion of normal or abnormal erythroid proliferation. Enumeration of blasts as a percentage of non-erythroid cells may lead to a diagnosis of AEL and mis-interpretation as disease progression.

Practical issues surrounding the explosion of tyrosine kinase inhibitors for the management of chronic myeloid leukemia.

The advent of tyrosine kinase inhibitors (TKIs) has drastically changed the treatment outcome of chronic myeloid leukemia (CML). Imatinib was the first TKI approved, and has been considered the standard of care for more than a decade. Second generation compounds, namely dasatinib and nilotinib, are highly effective in newly diagnosed patients as well as those who fail imatinib. Bosutinib and ponatinib have also become available as second line options. With five agents from which to choose, selecting a TKI has become a challenge. Multiple tests are now available to determine a patient's disease status, making the ideal monitoring strategy unclear. The gold standard for response to TKI therapy remains the achievement of complete cytogenetic response. This review will discuss the practical aspects of selecting a TKI and monitoring a patient once on therapy, including when to consider a treatment change. Other relevant issues, including cost, compliance, role of allogeneic hematopoietic cell transplantation, and discontinuation of TKIs will also be covered.

Patient adherence to tyrosine kinase inhibitor therapy in chronic myeloid leukemia.

Dramatically improved survival associated with tyrosine kinase inhibitor (TKI) therapy has transformed the disease model for chronic myeloid leukemia (CML) to one of long-term management, but treatment success is challenged with poor medication adherence. Many risk factors associated with poor adherence can be ameliorated by close monitoring, dose modification, and supportive care. Controlling risk factors for poor adherence in combination with patient education that includes direct communication between the health care team and the patient are essential components for maximizing the benefits of TKI therapy.