scholarly journals Cardiovascular (CV)-Related Hospitalizations and Associated Costs Among US Patients in Simplicity: An Observational Study of Patients with Chronic-Phase Chronic Myeloid Leukemia (CP-CML) in Routine Clinical Practice

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4151-4151
Author(s):  
Stuart L. Goldberg ◽  
Michael J. Mauro ◽  
Jorge E. Cortes ◽  
Scott Justin Keating ◽  
Hitesh Bhandari ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Hospital Stay ◽  
Cardiac Failure ◽  
Research Funding ◽  
The United States ◽  
Routine Clinical Practice ◽  
Categorical Variables ◽  
The Us ◽  
Equity Ownership

Introduction: CV events in CP-CML can negatively impact clinical and survival outcomes (Coutinho et al, Clin Lymphoma Myeloma Leuk, 2017), and CV-related hospitalization (hosp.) is costly (Nicholson et al, Clinicoecon Outcomes Res, 2016; Naccarelli et al, Clin. Cardiol, 2010). Mounting evidence suggests the common CV risk factors observed in individuals over the age of 60 combined with tyrosine kinase inhibitor (TKI) therapy may contribute to CV events in patients (pts) with CP-CML (Moslehi & Deininger, J Clin Oncol, 2015; Aghel et al, Vasc Health Risk Manag, 2017). SIMPLICITY is an ongoing observational study of pts with CP-CML receiving first-line (1L) TKIs in routine clinical practice in Europe and the United States (US). Here, we assess CV-related hosp. rates for SIMPLICITY pts in the US receiving 1L imatinib (IM), dasatinib (DAS), or nilotinib (NIL), including the incidence of hospital admissions and length of hospital stay (LOS), and related costs. Methods: In US pts, CV-related hosp. during 1L IM, DAS, or NIL therapy were identified from review of the electronic case report forms completed by clinicians. To control for possible confounding effects of multiple lines of TKI therapy, pts were followed from 1L TKI initiation to 30-days post-treatment or TKI switch, whichever came first. CV-related hosp. rates and LOS during 1L therapy were evaluated on a per-1,000-pt-year (PY) basis. For each CV event, mean total hosp. costs were derived from the 2016 Healthcare Cost and Utilization Project-National (Nationwide) Inpatient Sample database, to which professional fees from peer-reviewed literature were added; the medical component of the Consumer Price Index was used to convert 2016 costs to 2018 US dollars ($). Statistical comparisons for continuous variables were made using t-tests and the Mann-Whitney U test, and chi-square test for categorical variables. Time to first CV-related hosp. was evaluated using Kaplan-Meier methods with the log-rank test. Results: In the US, 808 pts were receiving 1L IM (n=243), DAS (n=301), or NIL (n=264); median follow-up was approximately 4 years (48.7-51.3 months). Age, treatment center type, and baseline fatigue differed significantly between the groups (p<0.05); stratification of duration of therapy in pts showed significant differences between the three TKI cohorts (p=0.0005; Table 1). The number of pts with CV-related hosp. was similar between IM (11 [4.5%]) and DAS (13 [4.3%]) cohorts, but higher in the NIL cohort (21 [8.0%]), equating to 16.6, 14.1, and 25.0 CV-related hosp. per 1,000 PY, respectively. Total CV-related LOS was 81, 36, and 98 days for the IM, DAS, and NIL groups, respectively, translating to 122.4, 46.5, and 116.9 hospital stay days per 1,000 PY. Most frequently experienced CV events were cardiac failure (IM=3.0, DAS=3.2, NIL=7.2 [per 1,000 PY]) and hemorrhage (IM=7.6, DAS=2.2, NIL=4.8 [per 1,000 PY]); rate of the latter was lowest in the DAS group. The rate of myocardial infarction-related hosp. was 1.5 and 2.4 per 1,000 PY for IM and NIL cohorts, respectively. Most inpatient days were due to cardiac failure (IM=13.6, DAS=10.8, NIL=56.1 [per 1,000 PY]) and hemorrhage (IM=80.1, DAS=5.4, NIL=22.7 [per 1,000 PY]); for DAS and NIL, cardiac failure caused the most inpatient days, whereas CV-related hemorrhage was responsible for the most IM-related hospitalization days. 43.8% of the observed CV-related hosp. occurred within 12 months of 1L TKI initiation, with 68.8% occurring by the 18-month mark (Figure 1). No difference in time to first CV-related hosp. with 1L TKI was seen between cohorts (p=0.4644). CV-related hosp. costs were highest among pts receiving IM or NIL, approximately twice that of the DAS cohort. Estimates derived from the product of mean hosp. cost per CV event and the rate of hosp. showed total CV hosp. costs of $475,058, $264,053, and $495,688 per 1,000 PY for IM, DAS, and NIL, respectively. Conclusions: CV-related events and hosp. were reported among US pts with CP-CML receiving 1L TKIs; the majority of which occurred within 18 months of TKI initiation. The incidence of CV-related hosp. and LOS, and mean hosp. costs were lowest among pts receiving DAS compared with the IM and NIL cohorts. The potential for added morbidity, healthcare utilization, and associated costs due to CV complications must be considered when making decisions on the appropriate TKI for individual pts with CP-CML. Disclosures Goldberg: Cancer Outcomes Tracking and Analysis (COTA) Inc.: Equity Ownership; Bristol-Myers Squibb: Consultancy; COTA: Equity Ownership. Mauro:Bristol-Myers Squibb: Consultancy; Novartis Oncology: Consultancy, Research Funding; Pfizer: Consultancy; Takeda: Consultancy. Cortes:Novartis: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Sun Pharma: Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; BiolineRx: Consultancy; Takeda: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Keating:Bristol-Myers Squibb: Employment. Bhandari:SmartAnalyst India (Pvt.) Ltd.: Employment, Other: I am an employee of SmartAnalyst India (Pvt.) Ltd., a subsidiary of SmartAnalyst Inc. which was contracted by Bristol-Myers Squibb for carrying out this analysis. Chen:Bristol-Myers Squibb: Employment.

scholarly journals Cardiovascular Hospitalization in Patients Treated with Dasatinib or Nilotinib in Simplicity, an Observational Study of Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients in Routine Clinical Practice

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4258-4258
Author(s):  
Michael J. Mauro ◽  
Clara Chen ◽  
Jorge E. Cortes ◽  
Carlo Gambacorti-Passerini ◽  
Ginny P Sen ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Hospital Stay ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Chronic Phase ◽  
Routine Clinical Practice ◽  
Kaplan Meier ◽  
The Us ◽  
Line Of Therapy

Abstract Introduction: The combined effect of cardiovascular (CV) risk and tyrosine kinase inhibitor (TKI) therapy may contribute to the incidence of CV events in patients (pts) with chronic phase chronic myeloid leukemia (CP-CML). CV events can affect the overall clinical outcomes and survival of CML patients, and hospitalization due to CV events is costly; analyzing the rates and risks of CV hospitalization in pts with CML receiving TKI therapy may help to inform treatment decisions and risk mitigation strategies and to minimize costs. SIMPLICITY (NCT01244750) is an ongoing observational study of CP-CML pts in routine clinical practice receiving first-line (1L) TKIs since 2010 in the US and Europe, exploring TKI use and management patterns in clinical practice. This analysis aims to evaluate rates of CV-related hospitalization and estimate related costs in pts treated with the second-generation TKIs dasatinib (DAS) and nilotinib (NIL). Methods: CV hospitalizations were identified retrospectively from events reported by SIMPLICITY investigators over the course of treatment with DAS or NIL, from the start of treatment (any line of therapy) to 30 days after the end of that line of therapy, or prior to the start of a subsequent line of TKI therapy, whichever was sooner. Pts were followed for a maximum of five years. Owing to the observational nature of SIMPLICITY, patients were not matched between cohorts and adjustments for covariates were not made. Kaplan-Meier methods with the log-rank test were used to estimate time to first CV hospitalization. Statistical comparisons were made using t-tests and the Mann-Whitney U test for continuous variables and chi square for categorical variables. Results: Overall, 825 pts received DAS (n=417) or NIL (n=408) as 1L therapy; 376 pts received DAS (n=214) or NIL (n=162) as second-line (2L) therapy; and 124 pts received DAS (n=63) or NIL (n=61) as third-line (3L) therapy. See table for patient baseline demographics and comorbidities. No significant differences were noted between the DAS and NIL cohorts. Median age was similar between the DAS and NIL groups at 56.2 and 54.1 years. At baseline, both groups had similar CV comorbidities. A significantly greater number of pts were treated in the US vs Europe (p=0.017). Investigators reported that, during 1L DAS and NIL therapy, 43% (n=357) of pts experienced a CV disorder: 45.3% (n=189) of DAS pts and 41.2% (n=168) of NIL pts (DAS vs NIL, p=0.28). Numbers of CV-related hospitalizations occurring during DAS and NIL therapy were 16 and 36, respectively, translating to 12.6 and 27.4 CV-related hospitalizations per 1000 pt years. Across 1L, 2L, and 3L (referred to here as 'all lines') of DAS and NIL therapy, 31 and 51 CV-related hospitalizations occurred, translating to 16.7 and 28.8 CV-related hospitalizations per 1000 pt years, respectively. The three most common CV-related reasons for hospitalization were congestive cardiac failure, atrial fibrillation and myocardial infarction. The figure shows Kaplan-Meier curves of time to first CV-related hospitalization for 1L therapy, for five years of follow-up. CV-related hospitalization at 5 years of follow-up was 5% for pts on 1L DAS, 7.5% for pts on 1L NIL, 5.7% for all lines of DAS and 8.5% for all lines of NIL. Durations of hospital stay related to CV disorders for pts on 1L DAS and 1L NIL were 68 days and 263 days, translating to 53.3 and 199.8 days in hospital per 1000 pt years. Durations of hospital stay related to CV disorders for pts on all lines of DAS and NIL were 107.4 days and 226.1 days, translating to 53.3 and 199.8 days in hospital per 1000 pt years. Incremental cost differences based on mean estimates will be presented. Conclusions: CV disorders and related hospitalizations were frequently seen in patients with CP-CML in SIMPLICITY. In these patients, NIL was associated with a rate of CV hospitalization up to double that associated with DAS and lengthier hospital stay. Owing to the survival benefits conferred by TKIs, it is critical to minimize and manage complications that may arise in treated pts; potential for greater morbidity and healthcare cost should be considered when making decisions about TKIs to use in individual pts, particularly those with preexisting CV comorbidities. Disclosures Mauro: Pfizer: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda: Consultancy; Novartis: Consultancy, Research Funding. Chen:Bristol-Myers Squibb: Employment. Cortes:Novartis: Consultancy, Research Funding; Arog: Research Funding; Astellas Pharma: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Daiichi Sankyo: Consultancy, Research Funding. Gambacorti-Passerini:Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy. Sen:ICON PLC: Employment. Gajavelli:Bristol-Myers Squibb: Employment. Davis:Bristol-Myers Squibb: Employment. Michallet:Octapharma: Membership on an entity's Board of Directors or advisory committees; Chugai: Consultancy; Novartis: Research Funding.

scholarly journals Treatment Patterns Among Adults with Newly Diagnosed Primary Immune Thrombocytopenia in the United States

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 497-497
Author(s):  
Karynsa Cetin ◽  
Leah J McGrath ◽  
Robert Overman ◽  
Diane Reams ◽  
Anjali Sharma ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Research Funding ◽  
Rescue Therapy ◽  
The United States ◽  
Advisory Board ◽  
Oral Steroid ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
The Us ◽  
Equity Ownership

Abstract Introduction: Immune thrombocytopenia (ITP) is a rare platelet disorder that can lead to an increased tendency to bleed. Recommended first-line therapies include corticosteroids, intravenous immunoglobulin (IVIg) and intravenous (IV) anti-D. An estimated two-thirds of adult patients with ITP will develop persistent or chronic disease (ITP lasting 3-12 months or >12 months, respectively). Several evidence-based options for second-line treatment exist, but no randomized trials have directly compared one therapy to another. Patterns of treatment in routine clinical practice therefore vary. There is a paucity of data on current real-world treatment dynamics in ITP, and such data could help identify gaps in care and inform future studies of real-world comparative effectiveness and safety. We described the types of treatments administered following an ITP diagnosis, as well as the subsequent occurrence of bleeding and requirement for rescue therapy among adults being managed in routine practice in the United States (US). Methods: We used electronic health record data from hematology clinics across the US (Flatiron Health, Inc.) linked to MarketScan® employer-based and Medicare Supplemental administrative health insurance claims databases (Truven Health Analytics, Inc.). We included patients aged 18 years or older with a new ITP diagnosis from January 1, 2011 through June 30, 2016, continuous enrollment in MarketScan prior to diagnosis, and no previous diagnosis of a secondary cause of thrombocytopenia. The cumulative incidence of each ITP treatment after diagnosis was estimated using competing risk models to account for deaths occurring before initiation. Estimates were provided specifically for 90 days and 1 year following diagnosis to describe treatment uptake in the newly diagnosed and persistent phases, respectively. The incidence of bleeding events and rescue therapy was quantified after the start of the more prevalent second-line therapies: rituximab, splenectomy, and thrombopoietin receptor agonists (TPO RAs) - eltrombopag and romiplostim. Rescue therapies (those that rapidly increase platelet counts in the setting of severe thrombocytopenia or active bleeding) included IV anti-D, IVIg, IV steroids, and platelet transfusions. Results: Among the cohort of 447 adults diagnosed with primary ITP, 47% were male, 61% were white, 32% were 65 years or older, and the median lowest platelet count in the 60 days prior to diagnosis was 85x109/L (IQR: 39, 125). Use of each ITP therapy by 90 days and 12 months post-diagnosis are provided in the Table. Oral corticosteroids were the most commonly used; the cumulative incidence of initiation was 41% by 90 days and 50% by 1 year following ITP diagnosis. IV steroids and rituximab were the next most frequently used medications (16% and 11% at 90 days; and 26% and 16% by 1 year, respectively). The cumulative incidence of the TPO RAs, eltrombopag and romiplostim, by 90 days was 3% and 7%, respectively, and by 1 year was 5% and 9%, respectively. Splenectomy was relatively rare (<4% by 1 year) as was use of all other non-rescue ITP medications (≤1% by 1 year). At 180 days post-ITP treatment initiation, rituximab initiators (N = 84) had a slightly lower incidence of bleeding overall (12% [6, 20]) than the other treatment groups (17% [6, 33] among 31 eltrombopag initiators; 19% [9, 31] among 49 romiplostim initiators; and 19% [6, 38] among 21 splenectomized patients). However, rituximab initiators had the highest cumulative incidence of rescue therapy use (48% [36, 58] compared with 29% [14, 46] for eltrombopag, 26% [14, 39] for romiplostim, and 19% [6, 39] for splenectomized patients). Subsequent oral steroid use was less frequent among TPO RA initiators than rituximab initiators or patients who underwent splenectomy. Conclusions: In this descriptive study of patients with primary ITP receiving care in the US, oral steroids were the most commonly used medication after diagnosis, reflecting their continued role as a frontline therapy. By 1 year after diagnosis, approximately 15% received rituximab, nearly 10% received romiplostim, and 5% received eltrombopag. Splenectomy was less common. Among the medical treatments, although bleeding risk overall appeared lowest in rituximab patients, oral steroid and rescue therapy use were lowest among the patients who initiated TPO RAs. Table. Table. Disclosures Cetin: Amgen Inc: Employment, Equity Ownership. Sharma:Amgen: Employment, Equity Ownership. Brookhart:Amgen Inc: Consultancy, Research Funding; NoviSci: Equity Ownership; Union Chimique Belge: Consultancy; GlaxoSmithKline: Consultancy; Merck: Consultancy; Genentech: Consultancy; TargetPharma: Consultancy; RxAnte: Consultancy; AstraZeneca: Research Funding. Altomare:Genentech: Consultancy; Ipsen: Other: Advisory Board Member; Amgen: Consultancy; Celgene: Other: Advisory Board Member; Novartis: Consultancy; Bayer: Consultancy; Incyte: Consultancy. Wasser:Amgen Inc: Consultancy; Novartis: Consultancy; Becton Dickinson: Equity Ownership; Abbott Labs: Equity Ownership; Biogen: Equity Ownership; Allergan: Equity Ownership; Eli Lilly: Equity Ownership; Incyte: Research Funding; Merck: Equity Ownership, Research Funding; Pfizer: Equity Ownership, Research Funding; Guardant: Research Funding.

scholarly journals Disease and Clinical Characteristics of Patients with Essential Thrombocythemia Enrolled in the MOST Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4306-4306
Author(s):  
Abdulraheem Yacoub ◽  
Roger M. Lyons ◽  
Srdan Verstovsek ◽  
Ryan Shao ◽  
David Tin Chu ◽  
...  
Keyword(s):  
United States ◽  
Observational Study ◽  
Board Of Directors ◽  
Essential Thrombocythemia ◽  
Research Funding ◽  
Clinical Characteristics ◽  
The United States ◽  
Advisory Committees ◽  
History Of ◽  
Equity Ownership

Abstract Introduction: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by clonal platelet production and an increased risk for thrombotic and hemorrhagic events. Limited real-world data exist regarding the clinical characteristics and treatment patterns of ET in the United States; most prior data have been generated outside the United States. The Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST) is an ongoing observational study being conducted to describe contemporary demographics, burden of disease, clinical management, and patient-reported outcomes in patients with specific risk categories of myelofibrosis (MF) or ET in the United States. This analysis describes the clinical characteristics of patients with ET currently enrolled in MOST. Methods: MOST is a multicenter, noninterventional, prospective, observational study in patients with a clinical diagnosis of specific risk categories of MF or ET (NCT02953704). Eligible patients with ET included high-risk patients (≥ 60 years of age and/or a history of thromboembolic events [TEs]), or low-risk patients currently receiving ET-directed therapy. Key exclusion criteria included participation in blinded investigational drug studies, life expectancy ≤ 6 months, or diagnosis of other malignancy. Data regarding disease and clinical characteristics are collected at usual-care visits over a planned 36-month observation period. Patient demographics and clinical characteristics at enrollment were described with descriptive statistics. Results: At data cutoff (May 18, 2018), 793 eligible patients were enrolled from 85 sites since November 29, 2016. The median age at enrollment was 70 (range, 24-95) years, 66.5% were female, and 89.8% were Caucasian. The median time from ET diagnosis to enrollment was 4.2 (range, 0.0-42.1) years with a proportion of patients diagnosed within 1 year (19.5%), 1 to < 5 years (35.0%), 5 to < 10 years (21.7%), or ≥ 10 years (23.8%) of enrollment. Approximately 40% of patients were retired and 42.7% were working full- or part-time at enrollment. A total of 212 patients (26.7%) had a history of TE at the time of enrollment. The type of TE was available for 148 patients, the most common was arterial events (53.4%); 33.1% had venous, and 13.5% of patients had both arterial and venous events. Six hundred and eighty-eight patients (86.8%) were classified as high-risk. Assessments at the time of ET diagnosis, among evaluable patients, included bone marrow biopsy (51.4%; 393/765) and mutational testing (77.2%; 590/764). Three hundred and forty-nine patients had mutation test results reported at the time of diagnosis; of patients with JAK2 V617F test results reported at the time of diagnosis (n = 313), 78.6% were positive for JAK2 V617F (Table 1). Laboratory values and peripheral blood counts were reported for patients with available data (Table 2). The majority of patients (87.9%) had received at least 1 ET-directed therapy prior to enrollment, which in some cases was the same medication the patient was receiving at the time of enrollment. At the time of enrollment, 740 patients (93.3%) were receiving at least 1 current ET-directed therapy, including HU (71.6%; 530/740), anagrelide (13.1%; 97/740), ruxolitinib (4.7%; 35/740), interferon (3.0%; 22/740), and busulfan (0.3%; 2/740). Of 793 patients, the most frequently occurring relevant comorbid conditions were hypertension (52.7%), history of smoking (44.7%), and hyperlipidemia (24.1%). Among 761 patients with ET-related symptoms assessed at diagnosis, the most common symptoms documented by healthcare providers included constitutional (22.9%), vasomotor (16.0%), and spleen-associated symptoms (3.9%), and pruritus (2.6%). Conclusions: Prior real-world data in ET has predominately been generated outside of the United States or has been reported from single institutional experiences. The MOST study will provide a more complete picture of the patient characteristics and outcomes of patients receiving ET-directed therapy in the United States. Ultimately, these data will be important for determining ET treatment gaps and areas of unmet need. Disclosures Yacoub: Cara Therapeutics: Equity Ownership; Inycte: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Ardelyx, INC.: Equity Ownership; Seattle Genetics: Honoraria, Speakers Bureau; Dynavax: Equity Ownership. Verstovsek:Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Italfarmaco: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy. Shao:ASH: Membership on an entity's Board of Directors or advisory committees; ASCO: Membership on an entity's Board of Directors or advisory committees. Agrawal:Incyte: Speakers Bureau. Sivaraman:Incyte: Employment. Colucci:Incyte: Employment, Equity Ownership. Yao:Incyte: Employment. Mascarenhas:Celgene: Membership on an entity's Board of Directors or advisory committees; Promedior: Research Funding; CTI Biopharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Research Funding; Merck: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Research Funding; Janssen: Research Funding.

scholarly journals Tyrosine Kinase Inhibitor (TKI) Switching Patterns during the First 12 Months in Simplicity, an Observational Study of Chronic-Phase Chronic Myeloid Leukemia (CP-CML) Patients (Pts) in Routine Clinical Practice

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 937-937
Author(s):  
Stuart Goldberg ◽  
Mauricette Michallet ◽  
Rudiger Hehlmann ◽  
Teresa Zyczynski ◽  
Aimee Foreman ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Clinical Practice ◽  
Observational Study ◽  
Clinical Research ◽  
Research Funding ◽  
Acquired Resistance ◽  
Routine Clinical Practice ◽  
Site Conditions ◽  
Tki Discontinuation

Abstract Introduction:SIMPLICITY (NCT01244750) is an ongoing observational study of CP-CML pts in routine clinical practice receiving first-line (1L) imatinib (IM) prior to 2010 (retrospective) or 1L IM, dasatinib (DAS) or nilotinib (NIL) since 2010 (prospective) in the US and Europe. Methods: This analysis was designed to identify baseline characteristics associated with TKI switching in pts pooled from the prospective and retrospective cohorts. Pts were characterized as 'early switchers' (who discontinued 1L TKI and switched to a second-line [2L] TKI within 3 months of TKI initiation) or 'late switchers' (who discontinued 1L TKI and switched to a 2L TKI between 3 and 12 months after TKI initiation). A comparator group of 'non-switcher' pts did not discontinue 1L TKI within 12 months of TKI initiation; 'early non-switchers' did not switch 1L TKI within the first 3 months and 'late non-switchers' did not switch 1L TKI between 3 and 12 months after TKI initiation. Logistic regression analysis was used to identify factors associated with early vs. late switching (gender, age at diagnosis ≥65 years, 1L TKI, region, reason for discontinuation). Results: By March 07 2016, 1494 pts were enrolled at 197 sites in 7 countries. Within 12 months of initiating 1L TKI 238 pts (16%) had switched to 2L TKI. Of switchers, 31% and 69% were early and late, respectively. Of the overall cohort, 1189 pts were early non-switchers and 1146 were late non-switchers. Most early switchers received IM as 1L TKI (49%), followed by NIL (32%) and DAS (19%); most late switchers received IM (56%), followed by DAS (26%) and NIL (18%). Fewer early non-switchers than switchers received IM as 1L TKI (43%), followed by NIL (28%) and DAS (28%); fewer late non-switchers than switchers received IM (44%), followed by DAS (28%) and NIL (28%). Most switchers were female; a higher proportion of female switchers was early vs. late (63% vs. 52%, respectively). In comparison, 43% of pts in both non-switching groups were female. Median ages of early and late switchers were 54 (interquartile range [IQR]: 46-68) and 58 (IQR: 46-69) years, respectively; median ages of early and late non-switchers were 56 (IQR: 46-68) and 56 (IQR: 45-67) years, respectively. Logistic regression analysis showed that pts who switched due to intolerance had greater odds of switching early compared with those who switched due to resistance (odds ratio = 3.49; 95% confidence interval: 1.11-10.98; p=0.0323). Among the 238 pts who switched 1L TKI, the main reason for 1L TKI discontinuation was intolerance (early switchers: 76%; late switchers: 71%; Figure). The most common intolerances leading to changes in early and late switchers varied by 1L TKI. Most common for IM early switchers (n=26) was general disorders/administration site conditions (including fatigue, edema, pain) and skin/subcutaneous disorders; for IM late switchers (n=53), gastrointestinal (GI) disorders, general disorders/administration site conditions and skin/subcutaneous disorders. Most common for DAS early switchers (n=10) was GI disorders; for DAS late switchers (n=36), respiratory/thoracic/ mediastinal disorders. Most common for NIL early switchers (n=19) was GI disorders; for NIL late switchers (n=25), GI disorders, general disorders/administration site conditions and skin/subcutaneous disorders. TKI resistance less commonly contributed to 1L TKI discontinuation. Primary and acquired resistance were seen in higher proportions of late than early switchers (Figure). In late switchers, primary resistance was a more common reason for discontinuation in IM pts vs. DAS pts or NIL pts (22%, 5% and 4%, respectively). Acquired resistance was only reported as a reason for discontinuation in IM-treated pts (early switchers: 0.3%; late switchers: 11%). Conclusions: Of pts switching or discontinuing 1L TKI in the first 12 months of therapy, around one third switched within the first 3 months; compared with late switchers and non-switchers these pts were more likely to be younger and female. TKI intolerance was the main reason for switching and was significantly associated with early switching. Resistance was a less common reason for changing TKI therapy and was seen more frequently after 3 months and among pts treated with IM. More research is necessary to make definitive conclusions about comparisons between TKI groups, given the small numbers of pts in the TKI cohorts and the non-controlled nature of the trial. Disclosures Goldberg: COTA Inc: Employment; Novartis: Consultancy; Neostem: Equity Ownership; Pfizer: Honoraria; Bristol-Myers Squibb: Speakers Bureau; Novartis: Speakers Bureau. Michallet:Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Astellas Pharma: Consultancy, Honoraria; MSD: Consultancy, Honoraria; Genzyme: Consultancy, Honoraria. Hehlmann:Bristol-Myers Squibb: Consultancy; Novartis: Research Funding; German CML-Group: Research Funding. Zyczynski:Bristol-Myers Squibb: Employment. Foreman:ICON Clinical Research: Employment. Calimlim:ICON Clinical Research: Employment. Paquette:Incyte: Consultancy, Honoraria; Novartis: Consultancy; Ariad: Consultancy. Gambacorti:Pfizer: Honoraria, Research Funding. Cortes:ARIAD: Consultancy, Research Funding; Bristol-Myers Squib: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Teva: Research Funding. Zagorska:Bristol-Myers Squibb: Employment. Rong:Bristol-Myers Squibb: Employment. Mauro:BMS: Consultancy; Ariad: Consultancy; Pfizer: Consultancy; Novartis: Consultancy.

Understanding United States (US) Treatment Practices for the Management of Chronic Myeloid Leukemia (CML) in Clinical Practice: A US Subgroup Analysis of the WORLD CML Registry.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2781-2781 ◽  
Author(s):  
Robert Hermann ◽  
Carole B. Miller ◽  
Rosalind Catchatorian ◽  
David S. Snyder ◽  
Solveig G. Ericson ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Research Funding ◽  
Practice Patterns ◽  
Disease Status ◽  
First Line ◽  
Employment Equity ◽  
Advisory Committees ◽  
The Us ◽  
The World ◽  
Equity Ownership

Abstract Abstract 2781 Background: The WORLD CML Registry, with sites in the US, Latin America, Asia-Pacific, the Middle East, Africa, Russia, and Turkey, is a multinational, prospective registry established to longitudinally assess global clinical practice patterns for the management of patients (pts) with CML. Here, we report updated results for the subgroup of pts at US sites and evaluate alignment of US practice patterns with current National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for CML (http://www.nccn.org). Methods: Pts (≥ 16 y of age) within 6 mo + 2 weeks of confirmed CML diagnosis were enrolled. Baseline demographics and medical history were collected at enrollment. Information on disease status and management was collected approximately every 6 mo or with a change in disease status or management. Adverse events (AEs) were collected only if they resulted in a dose/regimen change, nonadherence to treatment, or death. Results: This analysis includes 377 evaluable pts (those with confirmed informed consent forms and no protocol deviations) of 418 total pts enrolled in the US from February 2008 to December 31, 2010. Median age was 53 y (range, 18–91 y), with 26% ≥ 65 y of age. CML diagnosis was confirmed using hematologic (85%), bone marrow (84%), cytogenetic (82%), and molecular (polymerase chain reaction [PCR]; 52%) assessments. Nearly all pts (96%) were diagnosed in chronic phase (CP; Table). Most pts with CML-CP (73%) were treated with imatinib (Glivec®/Gleevec®) as first-line therapy (additional pts may have received first-line imatinib in a clinical trial). Median duration of imatinib treatment in CML-CP pts was 7.59 mo (range, 0.03–33.54 mo). In CML-CP pts (n = 363), imatinib dose was increased in 29 pts (8%; primary reasons included physician request [4%] and lack of efficacy [7%]), decreased in 32 pts (9%; primary reasons included AEs [5%] and physician request [3%]), and interrupted in 10 pts (3%; primary reasons included AEs [2%]). Regimen was switched from imatinib to nilotinib in 21 pts (6%; primary reasons included lack of efficacy [2%] and AEs [2%]) and to dasatinib in 20 pts (6%; primary reasons included AEs [2%], lack of efficacy [1%], and physician request [1%]). Disease burden over time on imatinib was most commonly assessed using blood counts (Table). Only 16% of pts had a molecular assessment at 3 mo; at later time points, 43%-64% of pts had molecular assessments. Cytogenetics was least common (done in 13% of pts at 3 mo and 25%-34% of pts at later time points). AEs reported in ≥ 1% of all pts in the analysis were nausea (3%), fatigue (2%), rash (2%), diarrhea (2%), headache (2%), thrombocytopenia (2%), neutropenia (1%), and dyspnea (1%). There were 17 deaths (5%) reported; 5 deaths were related to CML progression, 1 was related to CML treatment (necrotizing pneumonia), 7 were unrelated to CML treatment, and 4 had unknown causes. Conclusions: In the US, many pts treated with first-line imatinib did not have routine molecular or cytogenetic assessments, suggesting that many US physicians do not monitor their patients as recommended by the NCCN guidelines. These findings may reflect the lack of readily available molecular testing during part of the time period evaluated by this registry. Disclosures: Hermann: Novartis: Sponsor -paid expenses of reported trial Other. Miller:Novartis: Consultancy, Research Funding, Speakers Bureau, development of educational presentations Other; Incyte: development of educational presentations, development of educational presentations Other. Snyder:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees. Ericson:Novartis Pharmaceuticals Corp: Employment, Equity Ownership. Zernovak:Novartis Pharmaceuticals Corp: Employment, Equity Ownership. Juma:Novartis Pharmaceuticals Corp: Employment. Cortes:Novartis: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Ariad: Consultancy, Research Funding.

CLO19-029: Dosing Patterns of Nilotinib Use in SIMPLICITY, an Observational Study in Chronic Phase Chronic Myeloid Leukemia (CP-CML) Patients (Pts) in Routine Clinical Practice

2019 ◽  
Vol 17 (3.5) ◽  
pp. CLO19-029
Author(s):  
Jorge Cortes ◽  
Clara Chen ◽  
Michael Mauro ◽  
Neela Kumar ◽  
Catherine Davis ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Dose Reduction ◽  
Chronic Phase ◽  
Routine Clinical Practice ◽  
Myelogenous Leukemia ◽  
Categorical Variables ◽  
Imatinib Resistance ◽  
Dose Reductions ◽  
Dosing Patterns

Introduction: Dosing patterns of nilotinib (NIL) in chronic phase chronic myelogenous leukemia (CP-CML) patients (Pts) have not been well documented outside of clinical trials. SIMPLICITY (NCT01244750) is an ongoing observational study exploring tyrosine kinase inhibitor (TKI) use in routine clinical practice among CP-CML pts receiving TKIs in the US and Europe since 2010. This analysis reports NIL dosing patterns and explores predictors of dose reductions. A subset analysis focusing on the first-line (1L) approved dose of 300 mg twice daily (BID) will also be presented. Methods: Only SIMPLICITY pts receiving 1L NIL BID (n=349/408) were included. Baseline demographics and dosing patterns (starting dose, dose changes, time to dose reduction, and duration of therapy [DoT]) were analyzed descriptively. Statistical comparisons were made using t-tests, the Mann-Whitney U test for continuous variables, and chi-square for categorical variables. Logistic regression models were used to identify factors associated with dose reductions. Results: Of the 349 pts treated with 1L NIL, 281 (80.5%) started at the standard dose of 300 mg (BID) or the 400 mg (BID) dose for imatinib-resistance/intolerance, and 37 (10.6%) and 31 pts (8.9%) started on 150‒200 mg BID and 450‒800 mg BID. European pts were more likely to start on a dose >400 mg BID than US pts (P<.0001). Pts at academic centers were more likely to start on >400 mg BID than those treated at community practices (P<.0029). Among the pts starting NIL at 300 or 400 mg (BID) in 1L, 70.9% remained on these doses; 26.6% received a dose reduction (median time to dose reduction: 80.5 days); and 2.5% received a dose increase. Median DoT with NIL was 30.4 vs 43.9 months for pts with vs without a dose reduction (P=NS). The main reason for dose reduction was intolerance (n=51; 68.9%); in 51% of pts, a specific side effect was cited. Dose reductions were more likely in patients at academic centers (odds ratio=1.996; P=.021), but not in pts experiencing baseline fatigue (OR=1.799; P=0.072). Conclusions: Most pts treated with 1L NIL were started on 300 or 400 mg (BID); however, 1 in 4 pts required a dose reduction, most often due to intolerance. Physicians at academic centers were more likely to reduce the NIL dose than those in community practices. DoT with NIL for pts who received a dose reduction was shorter than that for those who did not. These findings will aid clinical decisions on dose optimization and maintaining response, whilst improving the patient quality of life.

scholarly journals Treatment Patterns and Outcomes of Multiple Myeloma (MM) with Chromosome Translocation (11;14) in United States (US) Routine Clinical Practice

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 40-43
Author(s):  
Shebli Atrash ◽  
Evelyn M. Flahavan ◽  
Tao Xu ◽  
Esprit Ma ◽  
Sudeep Karve ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Research Funding ◽  
Community Setting ◽  
B Cell Lymphoma ◽  
Chromosome Translocation ◽  
Routine Clinical Practice ◽  
Chromosome 1 ◽  
Test Results ◽  
Publicly Traded ◽  
The Us

Introduction: MM is an incurable disease with risk categorizations by cytogenetic abnormalities. Prognostic implications of chromosome translocation t(11;14)+ are important to inform development of biomarker-targeted therapies such as the B-cell lymphoma-2 (BCL-2) pathway inhibitors. This study aims to evaluate MM treatment (Tx) patterns and outcomes of t(11;14)+ compared with other cytogenetic cohorts in US routine clinical practice. Methods: A retrospective observational cohort study of the Flatiron Health database, which comprises de-identified electronic health record-derived patient (pt)-level data from over 280 community and academic cancer clinics in the US. Pts aged ≥18 years who received a first-line (1L) induction Tx within ≤60 days of MM diagnosis from 1/1/2011 to 1/31/2020, and were not enrolled in a clinical trial were identified at the start of each Tx line (index date) and followed up (f/u) until 1/31/2020. Only cytogenetic results by fluorescence in situ hybridization (FISH) were used to stratify the cohort into: t(11;14)+; standard risk, excluding t(11;14)+ (SR); and high risk, (HR; del 17p, t(4;14), t(14;16), t(14;20), chromosome 1 abnormalities as a proxy for 1q gain; and t(11;14) where it co-occurs). Descriptive analyses of pt characteristics and Tx were conducted. Kaplan-Meier analyses were used to evaluate median time to next treatment (TTNT) and overall survival (OS) with log-rank test for significance. The cohort was stratified by age ≤70/&gt;70 years (yrs) as a proxy for transplant eligibility. Results: Of 10,703 pts with MM in the database, 5982, 3059 and 1595 pts were eligible for 1L, second-line (2L), and third-line (3L) analysis, of which 76%, 84%, and 86%, respectively, had FISH test results before Tx initiation. 14% of pts with FISH test results were t(11;14)+, ~55% SR and ~35% HR. Included pts were predominately male (55%), ~90% treated in the community setting and ~16% African-American. Pts in the 3L cohort were younger at diagnosis with a median age (interquartile range) of 67 (59 ̶ 74) yrs compared with 69 (61 ̶ 76) yrs in both 1L and 2L. The 1L Tx pattern was consistent across cytogenetic cohorts with bortezomib (V), lenalidomide (R), dexamethasone (d) as the most common Tx (&gt;42%). Together, VRd, Rd, Vd, and cyclophosphamide (Cy) in combination with Vd represented ≥90% of 1L Tx (Figure 1). Across 2L cytogenetic cohorts, the most common Tx regimens (≥25%) were VRd and Rd. The use of regimens containing carfilzomib (K) and daratumumab (D) was emerging in 2L: KRd in 8% of t(11;14)+ and HR and 5% in SR; Kd 5% in all groups; DRd in 4% of t(11;14)+ and 3% in SR and HR (Figure 1). 3L Tx pattern was fragmented with different Tx regimens. Rd was the most common 3L Tx option: 9% in t(11;14)+, 10% in SR and 7% in HR (Figure 1). Across all lines of Tx, t(11;14)+ had similar Tx outcomes to SR, and HR had poorest outcomes (Table 1). Pts TTNT shortened as they advanced to later lines of Tx (Table 1). Although TTNT did not differ by age across lines of Tx, OS was superior in pts &lt;70 yrs across all 3 cytogenetic risk cohorts, especially in 1L where transplant in those ≤70 yrs vs &gt;70 yrs at diagnosis was 44% vs 11% for t(11;14)+, 47% vs 10% for SR and 49% vs 9% for HR. Conclusions: This study identified cytogenetic subgroups across 1L to 3L in a predominately community setting in the US. MM t(11;14)+ pts had similar 1L and 2L Tx patterns to SR and HR. Across all lines of Tx, the outcomes of t(11;14)+ and SR pts were comparable and better than HR pts. TTNT was reduced as pts advanced to later lines of Tx. Pts continuing to 3L Tx were younger at diagnosis, but there was not a clear-cut standard of care. While TTNT did not differ by age across lines of Tx, OS was superior in pts &lt;70 yrs across all 3 cytogenetic risk cohorts. This study sets the benchmark for novel treatment options, such as BCL-2 pathway inhibitors, primarily wherever available biomarker-driven therapy is considered appropriate. Disclosures Atrash: Takeda, Amgen, Karyopharm, BMS, Sanofi, Cellactar, Janssen and Celgene: Honoraria; BMS, Jansen oncology, Sanofi: Speakers Bureau; Amgen, GSK, Karyopharm.: Research Funding. Flahavan:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Roche Products Ltd.: Current Employment. Xu:F. Hoffmann-La Roche Ltd: Current Employment, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Ma:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. Karve:AbbVie: Current Employment, Current equity holder in publicly-traded company. Hong:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Jirau-Lucca:Genentech, Inc.: Current Employment; AbbVie: Current equity holder in publicly-traded company; BMS: Current equity holder in publicly-traded company; Celgene: Divested equity in a private or publicly-traded company in the past 24 months. Nixon:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company; F. Hoffmann-La Roche: Current Employment, Current equity holder in publicly-traded company. Ailawadhi:Takeda: Honoraria; Pharmacyclics: Research Funding; Cellectar: Research Funding; BMS: Research Funding; Medimmune: Research Funding; Phosplatin: Research Funding; Amgen: Research Funding; Celgene: Honoraria; Janssen: Research Funding.

scholarly journals A European Observational Study to Evaluate the Safety and the Effectiveness of Safinamide in Routine Clinical Practice: The SYNAPSES Trial

2021 ◽  
pp. 1-1
Author(s):  
Giovanni Abbruzzese ◽  
Jaime Kulisevsky ◽  
Bruno Bergmans ◽  
Juan C. Gomez-Esteban ◽  
Georg Kägi ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Observational Study ◽  
Routine Clinical Practice

scholarly journals Can serum ferritin levels predict the severity of dengue early?: an observational study

2019 ◽  
Vol 7 (3) ◽  
pp. 876
Author(s):  
Velammal Petchiappan ◽  
Thaha Mohammed Hussain ◽  
Saravanan Thangavelu
Keyword(s):  
Platelet Count ◽  
Clinical Practice ◽  
Observational Study ◽  
Hospital Stay ◽  
Serum Ferritin ◽  
Early Recognition ◽  
Dengue Infection ◽  
Elevated Serum ◽  
Severe Dengue ◽  
Elderly Subjects

Background: Dengue infection is a major public health threat; early recognition is crucial to improve the survival in severe dengue. Although there are various biomarkers to predict the severity of dengue, they are not routinely used in clinical practice for prognostication. We analyzed whether serum ferritin can be used to predict the severity at an earlier stage.Methods: A hospital based prospective observational study was done involving 119 dengue cases diagnosed by positive NS1 antigen or dengue specific serology (capture ELISA). Serum ferritin was measured in all at the time of diagnosis. Clinical and platelet count monitoring was done daily; classified as severe and non-severe according to 2009 WHO criteria.Results: Out of 119, 5 developed severe dengue; patients with severe dengue had significantly lower median platelet count (p<0.0001); higher ferritin levels (p=0.03) and hospital stay (p<0.0001) than non-severe group. Age had a significant negative co-relation with platelet count (r= -0.427; p<0.0001); positive correlation with ferritin levels (r=0.16; p=0.08) and hospital stay (r= 0.26; p=0.004) indicating that elderly subjects are at risk of severe disease. Serum ferritin levels negatively correlated with the platelet count (r= -0.51 p<0.001). High ferritin levels in severe cases are noted from day 4 of clinical illness.Conclusions: Elevated serum ferritin levels can be used as a potential early prognostic marker to predict the severity of dengue infection in clinical practice.

Sign in / Sign up

Export Citation Format

Share Document