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Background: Polycythemia vera (PV) and essential thrombocythemia (ET) are linked to increased risk of cardiovascular morbidity and mortality. In addition to the reduction in of arterial thrombotic events, statins may prevent venous thrombosis including among patients with cancer. As previous registry- and claims-based studies revealed that the use of statins may improve the survival of patients with various malignancies we evaluated their impact on outcomes of older adults with PV and ET., Methods: We identified 4010 older adults (aged 66-99 years at diagnosis) with PV (n = 1809) and ET (n = 2201) in a population-based cohort study using the Surveillance, Epidemiology, and End Results-Medicare database with median follow-up of 3.92 (interquartile range: 2.58-5.75) years. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) approaches were utilized to assess potential association between statins and overall survival. Multivariable competing risk models with death as a competing risk were used to evaluate possible relationship between statins and the incidence of thrombosis., Results: 55.8% of the patients used statins within the first year after PV/ET diagnosis, and statin use was associated with a 22% reduction in all-cause mortality (PSM: hazard ratio [HR] = 0.78, 95% confidence interval [CI]: 0.63-0.98, p = 0.03; IPTW: HR = 0.79, 95% CI: 0.64-0.97, p = 0.03). Statins also reduced the risk of thrombosis in this patient population (PSM: HR = 0.63, 95% CI: 0.51-0.78, p < 0.01; IPTW: HR = 0.57, 95% CI: 0.49-0.66, p < 0.01) as well as in PV and ET subgroups., Conclusions: These findings suggest that it may be important to incorporate statins into the therapeutic strategy for older adults with PV and ET., (© 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Tyrosine kinase inhibitor (TKI) use is critical in the care of patients with chronic myeloid leukemia (CML). Quantitative polymerase chain reaction (qPCR) testing for BCR-ABL1 every 3 months during the first year of TKI treatment is recommended to assure achievement of milestone response goals. Real-world evidence for the patterns of qPCR monitoring and TKI adherence in the older patient population is lacking. Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 1192 patients aged ≥66 years (median age, 74 years) with newly diagnosed CML who were followed up for ≥13 months from TKI initiation. In total, 965 patients (81.0%) had ≥1 test, with 425 (35.7%) and 540 (45.3%) of the patients tested during 1, 2, and ≥3 quarters (optimal monitoring) of the first year from TKI initiation, respectively. In multivariable analysis, diagnosis in later years and influenza vaccination before diagnosis, a proxy for health care access, were associated with optimal qPCR monitoring. Use of low-income subsidy and residing in census tracts with the lowest socioeconomic status were associated with less optimal monitoring. Patients with optimal monitoring were 60% more likely to be TKI adherent (odds ratio, 1.60; 95% CI, 1.11-2.31; P = .01) and had improved 5-year survival (hazard ratio, 0.66; 95% CI, 0.49-0.90; P < .01) than those without such monitoring. In this large, real-world study of CML management patterns, many older patients had suboptimal molecular monitoring, which was associated with decreased TKI adherence and worse survival., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Patients with classical Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary and secondary myelofibrosis (MF), are known to have an increased risk of second malignancies (SMs). Hydroxyurea (HU) is a guideline-recommended cytoreductive therapy for patients at high risk for MPNs. Controversy exists as to whether HU use is associated with a higher risk of SMs, including acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). We conducted a retrospective cohort study of older patients diagnosed with MPN (age ≥66 years) between 2010 and 2017 and included the data in the Surveillance, Epidemiology, and End Results Medicare-linked database. Multivariable competing risk analyses adjusting for patient characteristics were used to assess the impact of HU on the development of SM. We identified 4023 patients (1688 with PV, 1976 with ET, and 359 with MF) with a median age of 77 (interquartile range [IQR], 71-83) years at the time of MPN diagnosis. After a median follow-up of 3.25 (IQR, 2.10-5.00) years, 489 patients developed an SM (346 solid, 73 lymphoid, and 70 myeloid malignancies). The cumulative incidence probability of SM was 19.88% (95% confidence interval [CI], 17.16%-22.75%) among 2683 HU users and 22.31% (95% CI, 17.51%-27.47%) among 1340 nonusers, respectively (Gray's test, P < .01). We did not identify significant differences in the incidence of solid or hematologic SMs, including AML/MDS (hazard ratio, 1.33; 95% CI, 0.77-2.29; P = .30), between HU users and nonusers. Our results suggest that the use of HU does not increase the risk of SM in older patients with MPN., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Ivosidenib + azacitidine (IVO/AZA) is approved in the United States for newly diagnosed, older or intensive chemotherapy-ineligible patients with IDH1 -mutated acute myeloid leukemia. We created a partitioned survival analysis model to evaluate the health economic implications of this approval. Model outputs were used to calculate the incremental cost-effectiveness ratio (ICER) of IVO/AZA versus AZA. One-way and probabilistic sensitivity analyses were conducted. In the base case scenario, IVO/AZA and AZA resulted in life-time costs of $403,062 and $161,887, respectively. With an incremental gain of 0.95 QALYs, the ICER of IVO/AZA was $252,782/QALY. In sensitivity analyses, only a reduction in the price of IVO by 59.3% lowered the ICER to below $150,000/QALY and 99.95% of model calculations yielded ICERs of >$150,000/QALY. In a model in which all patients received IVO monotherapy after progression on AZA monotherapy, the ICER was $155,453/QALY and various model inputs that would make IVO/AZA cost-effective were identified.

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., (© 2022 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Existing studies regarding the role of DNA methyltransferase inhibitors (DNMTi) and lenalidomide in refractory anemia with ring sideroblasts (RARS) are limited. Using the surveillance, epidemiology, and end results-medicare database, we assembled a population-based cohort of older adults diagnosed with non-del(5q) lower-risk myelodysplastic syndromes during 2007-2015. Of 2167 patients, 30% had RARS. About 16% of RARS and non- ring sideroblasts (RS) patients received DNMTi. RARS patients were more likely to receive lenalidomide (11.1% vs. 7.1%, p  < 0.01). Among patients who were transfusion-dependent at treatment initiation, 55.6% of those treated with DNMTi only and 42.5% treated with lenalidomide only achieved red blood cell transfusion independence (RBC-TI) for a median duration of 21 and 12 weeks, respectively. RS status did not impact rate of RBC-TI. RARS patients had a significantly better survival, and the median survival of RARS patients varied by treatment group. In this population-based study of older RARS patients, DNMTi and lenalidomide were clinically active.

Background: The etiology of myeloproliferative neoplasms (MPN) is obscure, and no previous studies have evaluated the role of diet., Methods: In the NIH-AARP Diet and Health Study, a prospective cohort of 463,049 participants ages 50 to 71 years at baseline (1995-1996), we identified 490 MPN cases after a median follow-up of 15.5 years, including 190 with polycythemia vera (PV) and 146 with essential thrombocythemia (ET). We examined possible associations between various dietary factors and the risk of MPN as a group, as well as PV and ET, using multivariable Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) and adjust for potential confounding variables., Results: An increased risk was observed between fruit consumption and the risk of MPN overall (third tertile vs. first tertile, HR = 1.32; 95% CI, 1.04-1.67; P trend = 0.02) and PV (third tertile vs. first tertile, HR = 2.00; 95% CI, 1.35-2.95; P trend < 0.01). Increased risk of PV was also observed among those with high intake of sugar (HR = 1.77; 95% CI, 1.12-2.79), sugar from natural sources (HR = 1.77; 95% CI, 1.16-2.71), sugar from natural beverage sources (HR = 1.57; 95% CI, 1.08-2.29), and fructose (HR = 1.84; 95% CI, 1.21-2.79)., Conclusions: The intake of fat and protein did not appear to influence PV risk-neither did meat or vegetable consumption. None of the dietary factors studied was associated with the risk of ET. The role of sugar intake in the etiology of PV in older individuals warrants further investigation., Impact: Our results indicate that high sugar intake is associated with an increased risk of polycythemia vera., (©2020 American Association for Cancer Research.)

The hypomethylating agents (HMAs) azacitidine and decitabine have been the de facto standard of care for patients with acute myeloid leukemia (AML) who are unfit for intensive therapy. Using the Surveillance, Epidemiology, and End Results-Medicare linked database, we identified 2263 older adults (age ≥66 years) diagnosed with AML during 2005-2015 who received a first-line HMA; 1154 (51%) received azacitidine, and 1109 (49%) received decitabine. Median survival from diagnosis was 7.1 and 8.2 months (P < .01) for azacitidine- and decitabine-treated patients, respectively. Mortality risk was higher with azacitidine vs decitabine (hazard ratio [HR], 1.11; 95% confidence interval [CI], 1.01-1.21; P = .02). The findings were similar when evaluating only patients completing ≥4 cycles (42% of patients treated with either azacitidine or decitabine). These findings lost significance when evaluating those completing a standard 7-day schedule of azacitidine (34%) vs 5-day schedule for decitabine (66%) (HR, 0.95; 95% CI, 0.83-1.08; P = .43). Red blood cell (RBC) transfusion independence (TI) was achieved in one-third of patients with no difference between the 2 HMAs. In conclusion, the majority of older AML patients did not receive the minimum of 4 cycles of HMA often needed to elicit clinical benefit. We observed no clinically meaningful differences between azacitidine- and decitabine-treated patients in their achievement of RBC TI or survival., (© 2020 by The American Society of Hematology.)

Hypomethylating agents (HMA) showed overall survival (OS) benefits in patients with higher-risk myelodysplastic syndromes (HR-MDS) in clinical trials. We conducted a retrospective cohort study of Surveillance, Epidemiology, and End Results (SEER)-Medicare data of patients ≥66 years diagnosed with refractory anemia with excess blasts (RAEB), a proxy for HR-MDS, in 01/2001-04/2004 (pre-period) or 01/2006-12/2011 (post-period). Association between post-period diagnosis and OS was examined using propensity scores (PS)-matched samples. Among 1876 RAEB patients, median OS was 9 months and 30.8% received HMAs (3.6% in pre-period; 43.0% in post-period) with no association between post-period diagnosis and OS. In the top PS quartile, post-period diagnosis was associated with a 74% lower risk of death (Hazard ratio [HR] = 0.26, 95%-CI: 0.10-0.69, p  = 0.007), while outcomes were worse in the lowest PS quartile (HR = 2.80, 95%-CI: 1.06-7.36, p  = 0.037). HMA lead to a 3-month OS benefit for patients most likely to receive HMA but not for unselected RAEB cohort.

Cytarabine-anthracycline based intensive induction chemotherapy (IC) remains the standard of care for remission induction among fit patients with newly diagnosed acute myeloid leukemia (AML) in the United States (US). However, the mortality rate outside of clinical IC trials, predictors of death, and resource utilization during admission for IC have not been thoroughly examined. We used the Premier Healthcare database to identify adult patients (aged 18-89 years) treated with cytarabine-anthracycline-based IC during their first recorded inpatient stay for AML during the contemporary period of 2010 to 2017. We identified factors associated with inpatient death or discharge to hospice, using multivariable logistic regression models. We also assessed the patterns of inpatient healthcare resource utilization. A total of 6442 patients with AML from 313 hospitals who were treated with IC were identified. Median age was 61 years (interquartile range [IQR], 50-68 years), and 56% were men. Median length of stay was 29 (IQR, 25-38) days, with rates of in-hospital death and discharge to hospice of 12.3% and 3.7% (17.9% and 6.3% among patients aged ≥65 years), respectively. Predictors of in-hospital death or discharge to hospice included older age, geographic region, and lower hospital volume. During admission, 28.0%, 12.6%, and 4.0% of patients required treatment in intensive care units, mechanical ventilation, and dialysis, respectively. Despite improvements in supportive care in the contemporary era, inpatient mortality during first hospitalization for adult patients with AML treated with IC in the US remains high particularly among older patients., (© 2020 by The American Society of Hematology.)

Population level survival of patients with myelodysplastic syndromes (MDS) treated with hypomethylating agents (HMA) is inferior to clinical trials. Using SEER-Medicare data, we identified 2086 MDS patients diagnosed in 2004-13, aged ≥66 years at diagnosis, and receiving ≥1 HMA cycle after 2005. We used multivariate logistic regression and Cox proportional hazards models to assess the impact of provider experience on persistent HMA therapy and overall survival (OS), respectively. Median number of HMA cycles was 4 and median OS was 10 months. Thirty-two percent of patients were treated by providers with ≥1 prior HMA initiation in the last 2 years and were more likely to receive ≥4 cycles of HMA therapy (OR = 1.29, 95% CI = 1.06-1.57; p  = .01). No significant association was found between MDS or HMA initiation volume and survival. In conclusion, while HMA initiation volume was associated with persistent HMA treatment, neither MDS nor HMA initiation volumes were associated with OS in older MDS patients.

Background: The majority of patients with acute myeloid leukemia (AML) are aged >65 years at the time of diagnosis and are not actively treated. The objective of the current study was to determine the prevalence, temporal trends, and factors associated with no active treatment (NAT) among older patients with AML in the United States., Methods: A retrospective analysis was performed of Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 14,089 patients with AML residing in the United States who were diagnosed with AML at age ≥66 years during 2001 through 2013. NAT was defined as not receiving any chemotherapy, including hypomethylating agents. Multivariable logistic regression models were used to analyze sociodemographic, clinical, and provider characteristics associated with NAT., Results: The percentage of patients with NAT decreased over time from 59.7% among patients diagnosed in 2001 to 42.8% among those diagnosed in 2013. The median overall survival for the entire cohort was 82 days from the time of diagnosis. Patients treated with NAT had worse survival compared with those receiving active treatment. Variables found to be associated with higher odds of NAT included older age, certain sociodemographic characteristics (household income within the lowest quartile, residence outside the Northeast region of the United States, and being unmarried), and clinical factors (≥3 comorbidities, the presence of mental disorders, recent hospitalization, and disability)., Conclusions: Greater than one-half of older patients with AML residing in the United States do not receive any active leukemia-directed therapy despite the availability of lower intensity therapies such as hypomethylating agents. Lack of active therapy receipt is associated with inferior survival. Identifying predictors of NAT might improve the quality of care and survival in this patient population, especially as novel therapeutic options with lower toxicity are becoming available., (© 2019 American Cancer Society.)

Most patients with lower risk myelodysplastic syndromes (LR-MDS) become red blood cell (RBC) transfusion dependent at some time during their disease course. Hypomethylating agents (HMAs) are frequently used in this setting; however, reported rates of in RBC transfusion independence (TI) achieved with HMA therapy vary significantly between studies. Here we study the real-life clinical effectiveness of HMA in inducing RBC TI in anemic LR-MDS patients using the Surveillance, Epidemiology and End Results (SEER)-Medicare database. We find that approximately 40% of LR-MDS patients who were receiving RBC transfusions and 33% who were dependent on RBC transfusions at HMA initiation ultimately achieved TI. The receipt of ≥3 transfusions in the 8-week period before HMA initiation was significantly associated with lower odds of achieving TI. Our study provides important population level estimates of clinical effectiveness of HMAs in LR-MDS.

The current demand for adult hematologists in the United States is projected to exceed the existing supply. However, no national study has systematically evaluated factors affecting the adult hematology workforce. In collaboration with the American Society of Hematology (ASH), we performed a mixed methods study consisting of surveys from the annual ASH In-Service Exam for adult hematology/oncology fellows from 2010 to 2016 (8789 participants); interviews with graduating or recently graduated adult hematology/oncology fellows in a single training program (8 participants); and 3 separate focus groups for hematology/oncology fellowship program directors (12 participants), fellows (12 participants), and clinicians (10 participants) at the 2016 ASH annual meeting. In surveys, the majority of fellows favored careers combining hematology and oncology, with more fellows identifying oncology, rather than hematology, as their primary focus. In interviews with advanced-year fellows, mentorship emerged as the single most important career determinant, with mentorship opportunities arising serendipitously, and oncology faculty perceived as having greater availability for mentorship than hematology faculty. In focus group discussions, hematology, particularly benign hematology, was viewed as having poorer income potential, research funding, job availability, and job security than oncology. Focus group participants invariably agreed that the demand for clinical care in hematology, particularly benign hematology, exceeded the current workforce supply. Single-subspecialty fellowship training in hematology and the creation of new clinical care models were offered as potential solutions to these workforce problems. As a next step, ASH is conducting a national, longitudinal study of the adult hematology workforce to improve recruitment and retention in the field., (© 2019 by The American Society of Hematology.)

Background: Although provider-level volume is frequently associated with outcomes in cancers requiring complex surgeries, whether similar relations exist for cancers treated primarily with systemic therapy is unknown., Methods: Using a population-based cohort analysis of older adults diagnosed with diffuse large B cell lymphoma (DLBCL) during the years 2004-2011, we evaluated the association between oncologist volume and 4 clinical outcomes (receipt of any chemotherapy, receipt of an anthracycline-containing or equivalent regimen, early hospitalization, and overall survival). Our primary explanatory variable was lymphoma treatment volume, defined as the number of patients with newly diagnosed lymphoma for which an oncologist initiated therapy during a 12-month look-back period from each incident DLBCL case., Results: We identified 8247 Medicare beneficiaries who were newly diagnosed with DLBCL. Chemotherapy was administered to 6202 (75.2%) beneficiaries, and 71.4% of cytotoxic regimens contained an anthracycline. Beneficiaries who were treated by higher-volume oncologists had increased odds of receiving chemotherapy (adjusted odds ratio [aOR], 1.45; 95% confidence interval [CI], 1.24-1.70; P <.001) and of receiving an anthracycline-containing regimen (aOR, 1.26; 95% CI, 1.06-1.50; P = .009). Receiving care from a higher-volume provider was also associated with decreased hospitalization (aOR, 0.80; 95% CI, 0.69-0.95; P = .007) and improved survival (adjusted hazard ratio, 0.85; 95% CI, 0.79-0.92; P < .001)., Conclusion: In older adults diagnosed with DLBCL, receiving care from a provider with more experience treating lymphoma patients was associated with receipt of guideline-adherent therapy, reduced hospitalizations, and improved survival. Clinical volume may be an important factor in providing high-quality cancer care in the modern era., (© 2018 American Cancer Society.)

Background: Venous thromboembolism (VTE) occurs in 2% to 12% of patients with acute leukemia (AL) despite disease- and therapy-associated thrombocytopenia, and it can be associated with significant morbidity and mortality. Because of the few high-quality studies, there are no evidence-based guidelines for VTE prophylaxis in this patient population. We sought to determine the spectrum of practice regarding prevention of VTE in patients with AL during induction and consolidation therapies., Methods: We conducted a 19-question Web-based survey directed at North American providers caring for these patients. One hundred fifty-one of 215 responses received were eligible for analysis, with a response rate of 20.9% among physicians who treated leukemias., Results: Overall, 47% and 45% of providers reported using pharmacologic VTE prophylaxis during induction and consolidation phases, respectively. Approximately 15% of providers did not provide any VTE prophylaxis, while 36% used mechanical methods and ambulation. Among providers who did not recommend pharmacologic prophylaxis, the most commonly cited reasons were the perceived high risk of bleeding (51%), absence of data supporting use (38%), and perceived low risk of VTE (11%)., Conclusion: Large, prospective studies are needed to define the safest and most effective approach to VTE prevention in patients with AL., (Copyright © 2015 Elsevier Inc. All rights reserved.)