Practice patterns and real-life outcomes for patients with acute promyelocytic leukemia in the United States.

Acute promyelocytic leukemia (APL) is associated with a favorable long-term prognosis if appropriate treatment is initiated promptly. Outcomes in clinical trials and population-based registries vary; potential explanations include a delay in treatment and lower adherence to guideline-recommended therapy in real-world practice. We used the Vizient Clinical Data Base to describe demographic characteristics, baseline clinical characteristics, and treatment patterns in patients newly diagnosed with APL during the study period of April 2017 to March 2020. Baseline white blood cell count was used to assign risk status and assess treatment concordance with National Comprehensive Cancer Network guidelines. Logistic regression models examined adjusted associations between patient, hospital, disease characteristics, and adverse outcomes (in-hospital death or discharge to hospice). Among 1464 patients with APL, 205 (14.0%) experienced an adverse outcome. A substantial subset (20.6%) of patients did not receive guideline-concordant regimens. Odds of adverse outcomes increased with failure to receive guideline-concordant treatment (odds ratio [OR], 2.31; 95% confidence interval [CI], 1.43-3.75; P = .001), high-risk disease (OR, 2.48; 95% CI, 1.53-4.00; P < .001), and increasing age (≥60 years: OR, 11.13; 95% CI, 4.55-27.22; P < .001). Higher hospital acute myeloid leukemia (AML) patient volume was associated with lower odds of adverse outcome (OR, 0.44; 95% CI, 0.20-0.99 [for ≤50 vs >200 AML patients per year]; P = .046). In conclusion, in this large database analysis, 14.0% of patients newly diagnosed with APL died or were discharged to hospice. A substantial proportion of patients did not receive guideline-concordant therapy, potentially contributing to adverse outcomes.

Cost-effectiveness of first-line vs third-line ibrutinib in patients with untreated chronic lymphocytic leukemia.

The ALLIANCE A041202 trial found that continuously administered ibrutinib in the first-line setting significantly prolonged progression-free survival compared with a fixed-duration treatment of rituximab and bendamustine in older adults with chronic lymphocytic leukemia (CLL). In this study, we created a Markov model to assess the cost-effectiveness of ibrutinib in the first-line setting, compared with a strategy of using ibrutinib in the third-line after failure of time-limited bendamustine and venetoclax-based regimens. We estimated transition probabilities from randomized trials using parametric survival modeling. Lifetime direct health care costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs) were calculated from a US payer perspective. First-line ibrutinib was associated with an improvement of 0.26 QALYs and 0.40 life-years compared with using ibrutinib in the third-line setting. However, using ibrutinib in the first-line led to significantly higher health care costs (incremental cost of $612 700), resulting in an ICER of $2 350 041 per QALY. The monthly cost of ibrutinib would need to be decreased by 72% for first-line ibrutinib therapy to be cost-effective at a willingness-to-pay threshold of $150 000 per QALY. In a scenario analysis where ibrutinib was used in the second-line in the delayed ibrutinib arm, first-line ibrutinib had an incremental cost of $478 823, an incremental effectiveness of 0.05 QALYs, and an ICER of $9 810 360 per QALY when compared with second-line use. These data suggest that first-line ibrutinib for unselected older adults with CLL is unlikely to be cost-effective under current pricing. Delaying ibrutinib for most patients with CLL until later lines of therapy may be a reasonable strategy to limit health care costs without compromising clinical outcomes.

Cancer History, Health Insurance Coverage, and Cost-Related Medication Nonadherence and Medication Cost-Coping Strategies in the United States.

OBJECTIVES: To evaluate the relationship between cancer history and cost-related medication nonadherence (CRN) as well as cost-coping strategies, by health insurance coverage. METHODS: We used the 2013 to 2016 National Health Interview Survey to identify adults aged 18 to 64 years with (n = 3599) and without (n = 56 909) a cancer history. Cost-related changes in medication use included (1) CRN, measured as skipping, taking less, or delaying medication because of cost, and (2) cost-coping strategies, measured as requesting lower cost medication or using alternative therapies to save money. Separate multivariable logistic regressions were used to calculate the adjusted odds ratios (AORs) of CRN and cost-coping strategies associated with cancer history, stratified by insurance. RESULTS: Cancer survivors were more likely than adults without a cancer history to report CRN (AOR 1.26; 95% confidence interval [CI] 1.10-1.43) and cost-coping strategies (AOR 1.10; 95% CI 0.99-1.19). Among the privately insured, the difference in CRN by cancer history was the greatest among those enrolled in high-deductible health plans (HDHPs) without health savings accounts (HSAs) (AOR 1.78; 95% CI 1.30-2.44). Among adults with HDHP and HSA, cancer survivors were less likely to report cost-coping strategies (AOR 0.62; 95% CI 0.42-0.90). Regardless of cancer history, CRN and cost-coping strategies were the highest for those uninsured, enrolled in HDHP without HSA, and without prescription drug coverage under their health plan (all P<.001). CONCLUSIONS: Cancer survivors are prone to CRN and more likely to use cost-coping strategies. Expanding options for health insurance coverage, use of HSAs for those with HDHP, and enhanced prescription drug coverage may effectively address CRN.

Do cancer survivors change their prescription drug use for financial reasons? Findings from a nationally representative sample in the United States.

BACKGROUND: There is limited evidence from nationally representative samples about changes in prescription drug use for financial reasons among cancer survivors in the United States. METHODS: The 2011 to 2014 National Health Interview Survey was used to identify adults who reported ever having been told they had cancer (cancer survivors; n = 8931) and individuals without a cancer history (n = 126,287). Measures of changes in prescription drug use for financial reasons included: 1) skipping medication doses, 2) taking less medicine, 3) delaying filling a prescription, 4) asking a doctor for lower cost medication, 5) buying prescription drugs from another country, and 6) using alternative therapies. Multivariable logistic regression analyses were controlled for demographic characteristics, number of comorbid conditions, interactions between cancer history and number of comorbid conditions, and health insurance coverage. Main analyses were stratified by age (nonelderly, ages 18-64 years; elderly, ages ≥65 years) and time since diagnosis (recently diagnosed, <2 years; previously diagnosed, ≥2 years). RESULTS: Among nonelderly individuals, both recently diagnosed (31.6%) and previously diagnosed (27.9%) cancer survivors were more likely to report any change in prescription drug use for financial reasons than those without a cancer history (21.4%), with the excess percentage changes for individual measures ranging from 3.5% to 9.9% among previously diagnosed survivors and from 2.6% to 2.7% among recently diagnosed survivors (P < .01). Elderly cancer survivors and those without a cancer history had comparable rates of changes in prescription drug use for financial reasons. CONCLUSIONS: Nonelderly cancer survivors are particularly vulnerable to changes in prescription drug use for financial reasons, suggesting that targeted efforts are needed. Cancer 2017;123:1453-1463. © 2016 American Cancer Society.

Deferasirox therapy is associated with reduced mortality risk in a medicare population with myelodysplastic syndromes.

AIMS: Iron overload adversely affects patients with myelodysplastic syndromes (MDS), but benefits of iron chelation therapy have not been clearly demonstrated. We examined the association between deferasirox (DFX) therapy and mortality in transfusion-receiving Medicare patients. PATIENTS & METHODS: MDS patients from 2005 to 2008 were identified using ICD-9 codes from 100% Medicare claims. Patients receiving ≥20 blood units were observed until death or end of study. Marginal structural models were used for estimation. RESULTS: 3926 patients (10.1% used DFX) were observed for a mean of 48.8 weeks. Each incremental week of DFX was associated with a significant reduction in mortality risk (hazard ratio [HR]: 0.989; 95% CI: 0.983-0.996; p = 0.001). CONCLUSION: DFX therapy is associated with a reduced mortality risk among older MDS patients who received a minimum transfusion threshold.

Effect of erythropoiesis-stimulating agent policy decisions on off-label use in myelodysplastic syndromes.

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) are widely used to treat anemia associated with myelodysplastic syndromes (MDS) as an off-label indication. In early 2007, the U.S. Food and Drug Administration (FDA) released safety alerts and mandated label changes, and the Centers for Medicare & Medicaid Services (CMS) implemented a National Coverage Determination (NCD) in August 2007, dramatically restricting ESA coverage based on specific clinical parameters in non-MDS patients. We sought to determine the effect on ESA use in MDS, examining both treatment initiation and concordance with guidelines designed to target patients most likely to benefit from therapy. METHODS: We determined receipt of ESA within 6 months of diagnosis. For ESA recipients, we operationalized three National Comprehensive Cancer Network guidelines: serum erythropoietin determination before ESA initiation, transfusion-independent at ESA initiation, and initial ESA treatment episode of >= 8 weeks. Logistic regression models tested the effect of time (half-year increments pre-post the August '07 CMS NCD implementation), controlling for demographics and health status. RESULTS: 17,491 (61.1%) of 28,627 beneficiaries with MDS received ESAs. ESA use increased prior to the reference period (Jan.-July 2007), but declined beginning in August 2007, the date of NCD implementation (marginal probability =-0.05, p-value<0.01). Concordance with treatment guidelines changed during the observation period, with increased rates of serum erythropoietin levels, but declined in the other two guidelines. CONCLUSION: These results suggest a mixed pattern of change in the face of the FDA safety warnings and CMS NCD in MDS and highlight the importance of monitoring for unintended consequences of policy changes.

Fructose modulates cardiomyocyte excitation-contraction coupling and Ca²âº handling in vitro.

BACKGROUND: High dietary fructose has structural and metabolic cardiac impact, but the potential for fructose to exert direct myocardial action is uncertain. Cardiomyocyte functional responsiveness to fructose, and capacity to transport fructose has not been previously demonstrated. OBJECTIVE: The aim of the present study was to seek evidence of fructose-induced modulation of cardiomyocyte excitation-contraction coupling in an acute, in vitro setting. METHODS AND RESULTS: The functional effects of fructose on isolated adult rat cardiomyocyte contractility and Ca²âº handling were evaluated under physiological conditions (37°C, 2 mM Ca²âº, HEPES buffer, 4 Hz stimulation) using video edge detection and microfluorimetry (Fura2) methods. Compared with control glucose (11 mM) superfusate, 2-deoxyglucose (2 DG, 11 mM) substitution prolonged both the contraction and relaxation phases of the twitch (by 16 and 36% respectively, p<0.05) and this effect was completely abrogated with fructose supplementation (11 mM). Similarly, fructose prevented the Ca²âº transient delay induced by exposure to 2 DG (time to peak Ca²âº transient: 2 DG: 29.0±2.1 ms vs. glucose: 23.6±1.1 ms vs. fructose +2 DG: 23.7±1.0 ms; p<0.05). The presence of the fructose transporter, GLUT5 (Slc2a5) was demonstrated in ventricular cardiomyocytes using real time RT-PCR and this was confirmed by conventional RT-PCR. CONCLUSION: This is the first demonstration of an acute influence of fructose on cardiomyocyte excitation-contraction coupling. The findings indicate cardiomyocyte capacity to transport and functionally utilize exogenously supplied fructose. This study provides the impetus for future research directed towards characterizing myocardial fructose metabolism and understanding how long term high fructose intake may contribute to modulating cardiac function.

Trends in disparities in receipt of adjuvant therapy for elderly stage III colon cancer patients: the role of the medical oncologist evaluation.

BACKGROUND: Race disparities in adjuvant chemotherapy for stage III colon cancer patients have been documented, and medical oncologist evaluation is a critical step in the treatment process. Recent healthcare system and environmental changes may have reduced treatment gaps. OBJECTIVES: To examine differential rates of oncologist evaluation and conditional treatment, by race, and to determine whether changing evaluation and treatment patterns reduced disparities. RESEARCH DESIGN: Retrospective analysis of Surveillance Epidemiology and End Results-Medicare registry, enrollment, and claims data. SUBJECTS: Patients age >65, white or African American race, diagnosed with American Joint Committee on Cancer stage III colon cancer between 1997 and 2002. N = 7176. KEY MEASURES: Oncology specialty evaluation and management visit or chemotherapy claim; receipt of 5-fluorouracil based chemotherapy. Time periods are grouped into early (1997-1998), middle (1999-2000), and late (2001-2002). RESULTS: Initial adjusted oncologist evaluation rates were higher for whites compared with African American patients (58.7% vs. 42.9%), but changes over time reduced the race gap substantially. We did not find significant race-time trends in treatment rates conditional on oncologist evaluation. CONCLUSIONS: Race disparities in medical oncologist evaluations diminished over time, possibly in response to increased provider supply or changing patient and provider attitudes, but there was no parallel reduction in disparities in conditional treatment rates. Projected decreases in oncologist supply suggest the need for further research on this relationship. Research on the role of supplemental medical insurance on disparities in treatment is needed, particularly as the cost of recommended adjuvant therapy increases.