Real World Treatment Patterns in Chronic Myeloid Leukemia Patients Treated with Tyrosine Kinase Inhibitors in First Line in an Integrated Healthcare System

Abstract INTRODUCTION: BCR-ABL Tyrosine Kinase Inhibitors (TKI) have demonstrated efficacy in patients with chronic myeloid leukemia (CML) in the clinical trial setting. However, additional real world data evaluating first line TKI treatment patterns are still needed. Moreover, real world data captured within integrated, managed care organizations are scarce. This study evaluates treatment patterns among newly diagnosed CML patients initiated on frontline TKI therapy within the Kaiser Permanente Southern California (KPSC) integrated managed care organization. METHODS: A retrospective analysis was conducted using KPSC data between 1/1/2007 to 12/31/2014. Patients were identified with CML diagnosis from the KPSC cancer registry database during 1/1/2007 to 12/31/2013. Patients > 18 years on date of CML diagnosis, with no history of other prior cancers or stem cell transplant during the 12 months prior to diagnosis date were eligible for inclusion. Index date was defined as the date of the first TKI prescription identified during the period 1/1/2007 to 12/31/2013, and no history of TKI use in the prior 12 months. All patients had continuous membership and drug benefit eligibility 12 months prior to index date. Patients were followed from their index date until one of the following outcomes: 1) death, 2) disenrollment from health plan, 3) switch to another TKI, 4) discontinuation of index TKI therapy, or 5) end of study period of 12/31/2014. Discontinuation, switch and persistence of index TKI therapy were defined using a 60 day gap calculation: estimated date of depleting the second to last prescription supply, plus days' supply of the last prescription, plus 60 days. If a patient did not fill any TKI prescription before or during the 60 day gap, this was labeled as a discontinuation. If a patient filled a different TKI prescription before or during the 60 day gap, this was labeled as switch, and if a patient refilled their index TKI prescription, then this was labeled as continuation of index therapy. RESULTS: 216 patients were identified with incident CML and with first line TKI therapy: 19 (8.8%) on dasatinib, 189 (87.5%) on imatinib, and 8 (3.7%) on nilotinib. The mean age on diagnosis date was 53 years and 63% were male. The mean age for patients who initiated nilotinib was 45.5 years, 48.3 years for dasatinib, and 54.1 years for imatinib. The Charlson comorbidity index was highest for patients on dasatinib (3.0) but similar for the patients initiated on imatinib and nilotinib (2.51 and 2.50). The mean days until an outcome was identified was 347 (SD ± 311). 93 patients (43%) continued their index therapy; 95 patients (44%) discontinued their index therapy, 3 patients (1.4%) switched their index therapy, 7 patients (3.2%) died during follow up, and 18 patients (8.3%) disenrolled from the health plan. The majority of the patients were initiated on imatinib and 45% of these patients discontinued their index therapy per our study definition. CONCLUSIONS: 44% of incident CML patients initiated on TKIs discontinued therapy by an average of 347 days (less than 1 year) from the start of treatment. Imatinib was the initial TKI therapy for 87.5% of the patients. Additional data will be presented which may assist in healthcare decision making for those newly diagnosed CML patients initiating first line TKI therapy in a managed care setting. Figure 1: Summary Table of Outcomes from First Line Index TKI Therapy Disclosures Dimaano: Bristol Myers Squibb: Employment, Equity Ownership. Felber:Bristol Myers Squibb: Employment, Equity Ownership.

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Treatment patterns and characteristics of acute promyelocytic leukemia (APL) patients receiving arsenic trioxide (ATO) therapy in a real-world setting.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18522 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18522-e18522

Author(s):

Boxiong Tang ◽

Susan Gabriel ◽

Jifang Zhou ◽

Ashutosh K. Pathak ◽

Debra Irwin ◽

...

Keyword(s):

Real World ◽

Index Date ◽

Claims Data ◽

Treatment Patterns ◽

Chronic Obstructive ◽

Administrative Claims ◽

First Line ◽

Real World Data ◽

World Data

e18522 Background: Clinical trials have shown that low-risk APL patients had significantly better outcomes when receiving first-line all-trans retinoic acid (ATRA) + ATO compared with standard ATRA + chemotherapy. Few published studies have used real-world data to describe patients using ATO and their current treatment patterns. This study used United States (US) administrative claims data to describe treatment patterns and characteristics of patients receiving first-line ATO. Methods: This retrospective, observational cohort study used claims data from the MarketScan databases. As there is no ICD-9-CM diagnosis code for APL, ATO treatment was used as a surrogate for the diagnosis of APL since ATO is typically used only in APL patients. Patients were selected if they had ≥1 claims for ATO between January 1, 2000, and June 30, 2015. Date of first use was designated the index date. To identify first-line ATO initiation, patients with ATRA or other APL-indicated chemotherapy claims any time before the index date were excluded. Variable baseline and follow-up periods consisting of ≥3 months of pre-index and ≥30 days of post-index continuous enrollment in medical and pharmacy benefit were used. Results: In total, 331 patients were identified with a subset (n = 265) having ≥2 claims for ATO. The analysis focused on these 265 patients, 54% of whom were male. Mean age was 60.6 years; 45% were covered by Medicare. The most common comorbid conditions measured were diabetes (6%), chronic obstructive pulmonary disease (5%), and congestive heart failure (4%). The most commonly selected APL treatments administered during follow-up were ATRA (17%) and daunorubicin (9%) with the use of idarubicin, cytarabine, and mitoxantrone at less than 3%. Maintenance therapy with methotrexate or 6-mercaptopurine was observed in 7% and 6% of patients, respectively. Conclusions: This is one of the first studies to examine patient characteristics and treatment patterns for first-line ATO using real-world data. Further research is needed to evaluate outcomes for patients receiving ATO as first-line therapy and to re-evaluate treatment guidelines in light of these outcomes.

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Health Care Utilization and Costs Among Patients with Chronic Myeloid Leukemia Using Tyrosine Kinase Inhibitors

Blood ◽

10.1182/blood-2018-99-113809 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3537-3537

Author(s):

Joanna C Huang ◽

Sudeep Karve ◽

Sanchita Porwal ◽

Kushan Thakkar ◽

Thomas Marshall ◽

...

Keyword(s):

Tyrosine Kinase ◽

Emergency Room ◽

Tyrosine Kinase Inhibitors ◽

Health Plan ◽

Real World ◽

Index Date ◽

Kinase Inhibitors ◽

Employment Equity ◽

The Us ◽

Equity Ownership

Abstract INTRODUCTION: Tyrosine kinase inhibitors (TKIs) remain mainstay in the management of patients with CML. Several TKIs have been approved over the last two decades. Even though efficacy and safety remain as the primary drivers in treatment selection, in recent years importance has been placed on treatment affordability and economic burden associated with the long-term cancer treatments such as TKIs. However, current literature lacks real-world data on healthcare utilization (HCU) and costs among patients with CML using TKIs, which this study aims to address. METHODS: Retrospective cohort study was conducted using MarketScan Commercial, and Supplemental Medicare databases (2012-2016). Data includes medical and pharmacy utilization and costs for over 90 million individuals enrolled in employer-sponsored health-plans in the US. Data includes information on but not limited to medical diagnosis, procedures, drugs dispensed, date of service, health plan enrollment. Study involves adult patients (≥18 years) with ≥2 medical claims with a diagnosis of CML (ICD-9-CM: 205.10 - 205.12; ICD-10: C92.10-C92.12) and with a prescription claim for TKI. The date of first-TKI claim defined the index date. Patients were required to have continuous health plan enrollment ≥6 months before (defined as baseline period) and ≥6 months after index date. Selected patients were further classified into 5 sub-groups based on the index TKI observed (prescribed) post CML diagnosis (imatinib, dasatinib, nilotinib, bosutinib, ponatinib). Among the selected patients, all-cause HCU and costs were assessed from index date until end of database or end of enrollment, whichever occurred earlier. HCU and associated costs were assessed overall and by care settings including inpatient, emergency room, physician office, outpatient hospital, outpatient pharmacy, nursing facility and ancillary care. In addition, baseline (6 month) utilization and costs were assessed. Monthly and annual resource utilization and costs were reported for the overall CML cohort (across all TKI users) and by index TKI sub-groups. All costs were reported from a payer perspective (i.e., costs reimbursed by health plan) and adjusted to 2017 US dollars using the US consumer price index (medical component). All analyses were descriptive in nature. RESULTS: The study cohort included 2,213 CML patients. Distribution for the index TKI treatment was as follows: 41% imatinib, 36% dasatinib, 21% and 1% each for bosutinib and ponatinib. Mean age (standard deviation [SD]) of the cohort was 55 (15) years which was similar for individual TKI sub-groups. Majority of patients were males (55%) and 56% were enrolled in a preferred provider organization plan. The mean follow-up duration post-TKI initiation was 607 (442) days. The average baseline monthly all-cause costs were $4,365 with inpatient and pharmacy costs accounting for over 3/4th of the total costs (Figure 1). Post-TKI initiation the average monthly costs were twice ($9,288) compared with the baseline costs ($4,365) and the increase was primarily attributable to higher outpatient pharmacy costs ($6,619, accounted for 71% of total costs) (Figure 2). Monthly costs across other care settings (inpatient, outpatient, emergency room) were similar for the baseline and post-TKI initiation. On average patients had 1.4 office visits, 2.5 prescriptions and 0.7 hospital outpatient visits per month at baseline, which increased by 23%, 38% and 49%, respectively post TKI-initiation. During the 1st year post TKI-initiation, 17% patients in the overall CML cohort had at least 1 inpatient admission and this was consistent across individual TKI-sub-groups (except ponatinib, 50%). CONCLUSIONS: Findings on TKI utilization and costs in employer-sponsored health-plan database indicate that average costs and utilization were similar across the TKI sub-groups with pharmacy costs accounting for 71% of the total post TKI initiation costs. Overall, this study helps address the literature gap by providing recent real-world treatment care-setting specific utilization and costs among TKI uses and these data can be of value to several healthcare stakeholders including physicians, managed care plans and researchers in supporting clinical and formulary decisions and also serve as inputs for economic models. Finally, the sample sizes for ponatinib and bosutinb were small and results for these TKIs should be interpreted with caution. Disclosures Huang: ZS Associates: Employment; Novo Nordisk Inc: Equity Ownership; AstraZeneca: Research Funding. Karve:AbbVie: Employment, Equity Ownership. Porwal:ZS Associates: Employment. Thakkar:ZS Associates: Employment. Marshall:AbbVie: Employment, Equity Ownership. Rosenberg:AbbVie: Employment, Equity Ownership.

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Treatment Patterns and Outcomes in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Experience from a Single UK Centre

Blood ◽

10.1182/blood-2019-123664 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 2917-2917

Author(s):

John Radford ◽

Ellie White ◽

Felipe A. Castro ◽

Anshuman Chaturvedi ◽

Nathalie Spielewoy ◽

...

Keyword(s):

Real World ◽

Research Funding ◽

Cell Lymphoma ◽

Locally Advanced ◽

B Cell Lymphoma ◽

Treatment Patterns ◽

Small Cell Lung ◽

First Line ◽

Large B Cell Lymphoma ◽

Equity Ownership

Introduction: First-line (1L) therapy for diffuse large B-cell lymphoma (DLBCL) can cure ~60% of patients (pts), but ~10-15% do not respond and 20-25% relapse. Salvage chemotherapy with autologous stem cell transplant (ASCT) is standard for 'fit' pts with relapsed or refractory (R/R) disease. However ~50% of pts are ineligible for transplant and most who undergo ASCT will relapse; for these pts options are extremely limited. Here we evaluated R/R DLBCL treatment patterns and outcomes for pts managed at a single UK center to create a detailed 'real-world' comparator for novel therapies. Methods: A detailed retrospective analysis of medical records was undertaken for pts with DLBCL 2006-2017 and a R/R event 2011-2017. Additional eligibility criteria were: age ≥18 years; ≥1 prior anti-CD20 antibody-containing chemo-immunotherapy regimen; no history of high-grade transformation; and no lymphomatous CNS involvement. Pt characteristics, treatments, responses, and overall survival (OS) were reported by line (L) of therapy (2L, 3L, 4L+) in all pts and in refractory pts (defined as no response to or relapse within 6 months of last treatment). Results: Of 2025 pts diagnosed with DLBCL 2006-2017, 89 fulfilled eligibility including a R/R event 2011-2017: 89, 63, and 41 received 2L, 3L, and 4L+ treatment. Median age at 2L was 66 years (range 58-72). 58.4% (n=52) were male and 64.0% (n=57) were stage III/IV; 49.4% (n=44) were ABC subtype and 29.2% (n=26) were GCB. Systemic 2L therapies (≥5% incidence) included R-DHAP (20.2%; n=18), R-GDP (20.2%; n=18), DHAP (10.1%; n=9), R-GCVP (7.9%; n=7), and gemcitabine (5.6%; n=5). In 2L, 23.6% (n=21) of pts underwent ASCT. With each line, regimens became more diverse, with increased use of experimental therapies. Overall response rate was 46.1% in 2L, 27.0% in 3L, and 9.8% in 4L+. In refractory pts, it was 34.8%, 21.2%, and 7.9% (Table). OS is shown in the Figure and Table; 2-year OS was 30.6% in all R/R pts and 20.5% in refractory pts. Median OS was reduced in pts with low ECOG performance status or high LDH. Two-year OS was 71.4% in transplanted pts (n=23) and 16.3% in non-transplanted pts. Conclusions: Despite multiple treatment options, pts with R/R DLBCL have a very poor prognosis, highlighting the need for rapid introduction of more effective therapies. This can be facilitated by robust data such as these, which may be used for comparing outcomes of novel therapies with those expected at a given line of treatment in the 'real world', unrestricted by the requirements of a trial protocol. Results will be compared with those from the SCHOLAR-1 study (Crump et al. Blood 2017;130:1800-8) to provide greater clarity regarding R/R DLBCL treatment outcomes in the 'real world' setting. Disclosures Radford: Seattle Genetics: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Research Funding; AstraZeneca: Equity Ownership, Research Funding; GSK: Equity Ownership; BMS: Consultancy, Honoraria. Castro:F. Hoffmann-La Roche Ltd: Employment. Chaturvedi:Christie Hospital NHS Trust: Employment. Spielewoy:F. Hoffmann-La Roche Ltd: Employment. Gibb:Takeda: Research Funding. Surinach:Genesis Research: Employment. Shang:F.Hoffmann-La Roche AG: Employment. Wenger:F. Hoffmann-La Roche Ltd: Employment, Equity Ownership. OffLabel Disclosure: "Atezolizumab (atezo) is a programmed death-ligand 1 (PD-L1) blocking antibody. In the United States, atezo is approved for treatment of pts with locally advanced or metastatic urothelial carcinoma who are: not eligible for cisplatin-containing chemotherapy (chemo) and whose tumors express PDL-1, or are not eligible for any platinum-containing chemo regardless of PD L1 status; or have disease progression during or following any platinum-containing chemo, or within 12 months of neoadjuvant or adjuvant chemo. Atezo is also approved: in combination with bevacizumab, paclitaxel and carboplatin for first-line treatment of pts with metastatic non-squamous non-small-cell lung carcinoma (NSCLC) with no EGFR or ALK genomic tumor aberrations, and for pts with metastatic NSCLC who have disease progression during or following platinum-containing chemo; in combination with paclitaxel protein-bound for the treatment of adults with unresectable locally advanced or metastatic triple-negative breast cancer whose tumors express PD-L1; and in combination with carboplatin and etoposide, for the first-line treatment of adults with extensive-stage small cell lung cancer. Atezo is not approved for treatment of pts with multiple myeloma."

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Cardiac Events in Real-World Multiple Myeloma Patients Treated with Carfilzomib: A Retrospective Claims Database Analysis

Blood ◽

10.1182/blood.v128.22.3319.3319 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3319-3319 ◽

Cited By ~ 3

Author(s):

Ajai Chari ◽

Sanjay K. Aggarwal ◽

Khalid Mezzi ◽

Kenneth Wang ◽

Christopher Kim ◽

...

Keyword(s):

Real World ◽

Research Funding ◽

Cardiac Event ◽

Index Date ◽

Hospitalized Patients ◽

Cardiac Events ◽

Employment Equity ◽

Claims Database ◽

History Of ◽

Equity Ownership

Abstract Introduction: Multiple myeloma (MM) is a hematologic cancer that mostly affects elderly patients who are at increased risk for development of cardiac-related comorbidities due to age-, disease-, and treatment-related factors. In real world data, approximately 25-30% of MM patients are hospitalized for a cardiac event after MM diagnosis (Kistler et al. American Society Hematology 2012 Annual Meeting, poster 2916). The proteasome inhibitor, carfilzomib, is approved for treatment of patients with relapsed or refractory MM. In carfilzomib clinical trials, grade 3 or higher cardiac failure was reported for ~4% of patients (Stewart et al. NEJM 2015;372:142-52, Dimopoulos et al. Lancet Oncol 2016;17:27-38). In this retrospective analysis, we sought to evaluate the incidence rate (IR) of cardiac events in MM patients treated with carfilzomib in a real-world setting in the US and to describe differences in baseline characteristics between carfilzomib-treated MM patients who do and do not have cardiac events. Methods: Newly-diagnosed MM patients with symptomatic disease were identified in the Truven MarketScan claims database from 1/1/05 to 6/30/15 using an algorithm validated for ascertainment of MM patients in claims data (Princic et al. Blood 2015;126:4521). All carfilzomib-treated patients were included in the analysis. The first dose of carfilzomib was the index date. The baseline period was 12 months prior to the MM diagnosis date to the index date. Cardiac events (hypertension, heart failure, ischemic heart disease, arrhythmias and conduction disorders, and cardiomyopathy) were identified during baseline by inpatient (IP) or outpatient (OP) claims and after index date by primary diagnosis on IP claims (hospitalized events). Logistic regression was used to estimate baseline covariates associated with any cardiac event. Due to sample size constraints, multivariate regression was not performed. The incidence rate (IR) per 1000 patient-years (PYRs) and associated 95% confidence interval (CI) of hospitalized cardiac events during carfilzomib treatment which included 30 days after the last carfilzomib dose were calculated among patients without a history of the corresponding hospitalized event during the baseline period. Results: The cohort included 498 MM patients treated with carfilzomib; 108 (22%) patients had ≥1 cardiac event identified by both IP and OP claims and 24 (5%) had ≥1 hospitalized cardiac event. Of the 24 hospitalized patients, 14 were hospitalized during carfilzomib treatment (median days to onset = 104) and 8 were hospitalized after carfilzomib treatment (>30 days post dosing; median days to onset = 284). The median age (range) of the 24 patients with hospitalized cardiac events and those with no hospitalized cardiac claims (n=474) was 62 (37, 79) and 61 (36, 96) years, respectively (Table). Baseline medical history of any cardiac event was evident for 92% of hospitalized patients and 84% of non-hospitalized patients. Among hospitalized patients, 25% were over 75 years as compared with 13% of non-hospitalized patients. In univariate analysis, patients with baseline amyloidosis, hypertensive chronic kidney disease, and chronic kidney disease had higher odds of having a hospitalized cardiac event. No significant differences were seen in the proportion of patients with or without a hospitalized cardiac event when evaluated by line of therapy or by carfilzomib treatment regimen (monotherapy or combination). Among patients aged 75+ years, 8.7% were hospitalized, while 2.5% and 4.9% of 65-74 and 18-64 year old patients were hospitalized, respectively (Table). IR per 1000 PYRs [95% CI] among the 14 carfilzomib-treated MM patients hospitalized for any cardiac event during the carfilzomib treatment period was 89.7 (49.0; 150.5) - see Figure for IRs of specific cardiac events. Conclusions: Among carfilzomib-treated patients in a US claims database, hospitalization for a cardiac event was uncommon (~5%) and does not exceed what has been observed in MM patients. Patients at highest risk for cardiac hospitalizations had a history of amyloidosis or chronic renal failure. Additional analyses in much larger populations are needed to better understand risk factors for these events. Disclosures Chari: Array Biopharma: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Amgen Inc.: Honoraria, Research Funding; Novartis: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Pharmacyclics: Research Funding; Janssen: Consultancy, Research Funding. Aggarwal:Amgen: Employment, Equity Ownership. Mezzi:Amgen Inc.: Employment, Equity Ownership. Wang:Amgen Inc.: Employment, Equity Ownership. Kim:Amgen Inc.: Employment, Equity Ownership. Zhu:Amgen Inc.: Consultancy. Braunlin:Amgen Inc.: Employment, Equity Ownership. Werther:Amgen Inc.: Employment, Equity Ownership. Mikhael:Abbvie: Research Funding; Celgene: Research Funding; Sanofi: Research Funding; Onyx: Research Funding.

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Serious infections and cardiovascular complications among patients with chronic lymphocytic lymphoma treated with first-line ibrutinib or bendamustine/rituximab.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e19503 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e19503-e19503

Author(s):

Debra E. Irwin ◽

Stephen Thompson ◽

Rinat Ribalov ◽

Azhar Choudhry

Keyword(s):

Real World ◽

Index Date ◽

Cardiovascular Complications ◽

Administrative Claims ◽

First Line ◽

Real World Data ◽

World Data ◽

Serious Infections ◽

Baseline Characteristics

e19503 Background: Clinical trials have shown positive outcomes associated with ibrutinib monotherapy (IM) and bendamustine / rituximab combination (BR) therapy in patients with chronic lymphocytic lymphoma (CLL) compared to other standard treatments, but limited real-world data exist. This study evaluated serious infections and cardiovascular complications in CLL patients treated with first-line IM or BR therapy using US real-world data. Methods: Administrative claims from the MarketScan® Research Databases were used to identify adult patients enrolled in commercial or Medicare supplemental insurance plans based on a first prescription fill of IM or BR therapy (the index date) from 2/1/14 to 9/1/19. Patients were diagnosed with CLL, treatment naïve, and continuously enrolled for ≥12 months prior to and following the index date. Serious infections and cardiovascular complications requiring hospitalization (diagnosis code in any position) were evaluated during a fixed 12-month follow-up period. Statistical differences in outcome distributions between the treatment groups were tested. Multivariate logistic regression models for lower respiratory tract infection (LRTI) and atrial fibrillation (AF) were also conducted to determine the adjusted odds of hospitalization. Results: Of 2,138 CLL patients, 810 had IM and 512 had BR as index therapy with ≥12 months of follow-up data. Patients receiving IM were older and more likely to have had an LRTI during baseline compared to BR patients, otherwise both groups had similar baseline characteristics. Hospitalization for serious infections was more common during follow-up among IM patients than BR patients (17.7% vs. 13.1%; p = 0.027). Specifically, 10.2% of IM patients had a bacterial infection hospitalization compared to 5.7% of BR patients (p = 0.004) and 10.7% of IM patients had a LRTI hospitalization compared to 6.6% of BR patients (p = 0.012). After adjusting for baseline characteristics, IM patients did not have significantly higher odds of a LRTI hospitalization (OR = 1.51; p = 0.069). Hospitalization for cardiovascular complications was more common during follow-up among IM patients than BR patients (18.3% vs. 11.9%; p = 0.002). Specifically, 8.4% of IM patients had an AF-related hospitalization versus 2.7% of BR patients (p < 0.001). After adjusting for baseline characteristics, IM patients were more likely to have a hospitalization for AF versus BR patients (OR = 3.89; p < 0.001). Conclusions: In a real-world setting, serious infections and cardiovascular complications were more common among CLL patients treated with first-line IM compared to BR during 12 months of follow-up. IM patients were more likely than BR patients to have an inpatient admission due to AF after adjusting for other patient characteristics.

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Real-World Treatment Patterns and Outcomes Among Patients with Hairy Cell Leukemia

Blood ◽

10.1182/blood.v126.23.2125.2125 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2125-2125

Author(s):

Sudeep Karve ◽

Victoria Divino ◽

Andrew Gaughan ◽

Mitch DeKoven ◽

Guozhi Gao ◽

...

Keyword(s):

Health Plan ◽

Real World ◽

Index Date ◽

Treatment Patterns ◽

Second Line ◽

First Line ◽

Second Line Therapy ◽

First Line Therapy ◽

Line Therapy

Abstract Background and Objective : Hairy cell leukemia (HCL) is a rare condition and accounts for ~2% of all leukemia cases in the US. NCCN guidelines recommend first-line agents including pentostatin and cladribine among patients with HCL. However, a paucity of data exists with regard to real-world treatment patterns among patients with HCL. Current study evaluates treatment patterns and associated clinical outcomes among patients with HCL using a large US administrative claims database. Methods : This retrospective observational study was conducted using the IMS Health PharMetrics Plus Health Plan Claims Database (2006-2014), which includes over 150 million unique health plan members across the US and is nationally representative of the commercially-insured US population. Data includes date stamped medical and pharmacy records along with information on health plan enrollment. Individuals with at least 2 medical claims with a diagnosis for HCL (identified using ICD-9-CM cod: 202.4x) were selected and the first observed claim defined the "index date." Patients <18 years of age at index date or with other malignancies during 6 months (the "pre-index period") prior to index date were excluded. Patients were required at least 90 days of continuous enrollment (the variable "follow-up period") in the health plan post index date with exception of patients who died within 3 months of diagnosis. Patients were followed until death (recorded on inpatient discharge disposition), end of enrollment or end of database, whichever occurred earlier. Study measures including patient demographic and baseline clinical characteristics, line of therapy (LOT), treatment patterns, relapse (receipt of same or new regimen in subsequent LOT following a gap of 365 days) and refractory disease (receipt of same or new regimen where the gap of two adjacent LOTs was <365 days) and post-treatment complications were assessed during the follow-up period. All analyses were descriptive in nature. Results : The study cohort included 749 patients after applying the selection criteria (mean follow-up from diagnosis 32 months). At diagnosis, the mean age (standard deviation) of the study cohort was 56 (10) years and majority of patients were male (77%). Mean baseline comorbidity burden (assessed using Charlson Comorbidity Index score) was 0.8 (1.1) with hypertension (24%) and aplastic anemia (22%) being the two most common co-morbidities. Only 38% (n=282) of patients received first-line chemotherapy post diagnosis. Majority initiated first-line cladribine (76%) as a single agent, while 9% had evidence of single agent pentostatin. Mean time to initiation of first-line therapy from diagnosis was 132 (294) days and average time on first-line therapy was 34 (104) days. Among patients with first-line therapy 14% received second-line therapy and rituximab (53%) and cladribine (21%) were frequently observed second-line agents. Post first-line therapy, mean time to initiation of second-line therapy was 303 (406) days. Among second-line initiators, 76% had refractory disease and 24% had relapsed following first-line. Neutropenia and fever were frequently reported complications while on chemotherapy. Conclusion : The real-world chemotherapy utilization patterns observed in this study are consistent with the NCCN guidelines with cladribine and pentostatin being the agents of choice for first-line therapy. Following diagnosis, more than one-third of patients initiated chemotherapy and only a small proportion of these received second-line chemotherapy suggesting durable response with first-line therapy. Limited follow-up post first-line therapy may have impacted the proportion of patients initiating second-line therapy as well as categorization of refractory and relapse disease. Disclosures Karve: AstraZeneca: Employment. Divino:IMS Health: Employment, Other: IMS Health received funding from AstraZeneca for this study. Gaughan:AstraZeneca: Employment. DeKoven:IMS Health: Employment, Other: IMS Health received funding from AstraZeneca for this study. Gao:MedImmune: Employment. Lanasa:MedImmune: Employment.

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Assessment of Treatment Patterns and Adverse Events Among Patients with Chronic Myeloid Leukemia Using Tyrosine Kinase Inhibitors

Blood ◽

10.1182/blood-2018-99-112695 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3585-3585

Author(s):

Sudeep Karve ◽

Joanna C Huang ◽

Nikhil Ranade ◽

Sanchita Porwal ◽

Monali Desai ◽

...

Keyword(s):

Clinical Trial ◽

Adverse Events ◽

Cardiovascular Events ◽

Kinase Inhibitors ◽

Treatment Patterns ◽

First Line ◽

Employment Equity ◽

Equity Ownership

Abstract INTRODUCTION: Chronic myeloid leukemia (CML), a myeloproliferative neoplasm is primarily treated using tyrosine kinase inhibitors (TKIs). Several next-generation TKIs (dasatinib, nilotinib, bosutinib, ponatinib) have been approved since the first approval of imatinib in 2002. With varying safety profiles, data on non-trial long-term TKI use and associated adverse events (AE) can aid in clinical decision making. Using population based data sources the current study assessed treatment patterns and AEs in a non-trial setting among TKI users with CML. METHODS: A retrospective cohort analysis was conducted using MarketScan Commercial, and Supplemental Medicare databases (2012-2016). Data includes details on medical (e.g., date of diagnosis, diagnosis codes, procedures) and pharmacy (e.g., drug dose, duration, strength) utilization for over 90 million individuals enrolled in employer-sponsored health-plans in the US. Patients with a prescription claim for TKI along with at least 2 medical claims on separate dates with a diagnosis code for CML (ICD-9-CM: 205.10 - 205.12; ICD-10: C92.10-C92.12) were selected. Patients were aged ≥18 years at TKI initiation and had continuous health plan enrollment ≥6 months before and ≥6 months after TKI initiation. Patients were followed from TKI initiation until health plan disenrollment or end of database, whichever occurred earlier (defines follow-up period). TKI treatment patterns including initial dose, initial and total TKI treatment duration, treatment switching and discontinuation were assessed. Frequency and proportion for incident (i.e. newly observed conditions) AEs including rash, bleeding, gastrointestinal disorders (nausea, vomiting, diarrhea), tumor lysis syndrome and cardiovascular events (CHF, arrhythmia, peripheral arterial occlusive disease, cerebrovascular events) and post-AE outcomes (switching, discontinuation, dose reduction) were assessed. AE list was developed based on commonly reported events in clinical trials involving TKIs for CML and clinical judgement. All analyses were descriptive in nature. RESULTS: Study included 2,213 CML patients with mean age (standard deviation [SD]) of 55 (15) years, of which 55% were male and 55% had ≥2 co-morbid conditions. Post CML diagnosis, first-line of TKI initiated was imatinib (41%), dasatinib (36%), nilotinib (22%), and bosutinib and ponatinib (1% each). The average (SD) follow-up duration post TKI initiation was 607 (442) days. Mean (SD) duration of first-line TKI prescription was 392 (383) days. 61% of patients continued initial TKI during the follow-up period, 7% discontinued and 32% switched/re-initiated TKI (Figure 1). 39.2% patients had at least 1 incident AE while on index TKI therapy. GI disorders (20.4%) were the most commonly observed AE, followed by cardiovascular events (14.6%), rash (8.4%), bleeding (8.0%), and TLS (0.2%). The average (SD) time to GI disorders, bleeding, cardiovascular event, rash, and TLS was 242 (274) days, 238 (272) days, 219 (261) days, 222 (255) days, and 223 (285) days, respectively. The rates of discontinuation, treatment switch or dose reduction were largely similar across all AEs (Figure 2). The mean duration on any TKI (all-lines of therapy) was 561 (438) days. The most commonly observed AEs on while of TKI therapy (irrespective of line of therapy) were GI disorders (24.7%), followed by cardiovascular events (17.3%), rash (11.5%), bleeding (10.1%) and TLS (0.5%). CONCLUSIONS: The study helps address the current literature gap of long-term treatment patterns and AE among patients with CML using TKIs in a non-clinical trial setting. During follow-up 46% patients experienced at least 1 incident AE while on TKI therapy. Majority of patients (61%) continued same TKI therapy following AE. The type and rate of AE were similar following first-line therapy and anytime on TKI (any-line) during the follow-up period. Study results may not be comparable to clinical trial findings due to certain limitations; e.g., this study did not capture all adverse events but assessed incident AE based on a pre-specified list. Also, due to limitations of administrative claims data, assessment of AE grade was not feasible. However, findings from this study can complement clinical trial data in selection of TKIs for long-term use in real-world setting and can also be of value in selecting TKIs for future clinical studies involving novel combinations in CML. Disclosures Karve: AbbVie: Employment, Equity Ownership. Huang:ZS Associates: Employment; Novo Nordisk Inc: Equity Ownership; AstraZeneca: Research Funding. Ranade:ZS Associates: Employment. Porwal:ZS Associates: Employment. Desai:AbbVie: Employment, Equity Ownership. Rosenberg:AbbVie: Employment, Equity Ownership.

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Real-world incidence and costs of serious infections and cardiovascular complications among patients with indolent non-Hodgkin lymphoma treated with first-line ibrutinib or bendamustine/rituximab.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e19528 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e19528-e19528

Author(s):

Debra E. Irwin ◽

Stephen Thompson ◽

Rinat Ribalov ◽

Azhar Choudhry

Keyword(s):

Hodgkin Lymphoma ◽

Real World ◽

Index Date ◽

Cardiovascular Complications ◽

Hospitalized Patients ◽

First Line ◽

Real World Data ◽

Non Hodgkin Lymphoma ◽

Serious Infections

e19528 Background: Patients with Indolent non-Hodgkin lymphoma (iNHL) have shown positive outcomes with ibrutinib monotherapy (IM) as well as bendamustine/rituximab combination (BR) therapy, but no studies have reported on patient outcomes using real-world data. The current analysis evaluated serious infections and cardiovascular complications in iNHL patients treated with first-line IM or BR therapy using US real-world data. Methods: Administrative claims from the MarketScan® Research Databases were used to identify adult patients enrolled in commercial or Medicare supplemental insurance plans based on a first prescription fill of IM or BR therapy (the index date) from 2/1/14 to 9/1/19. Patients included in the study were diagnosed with iNHL, were treatment naïve, and were continuously enrolled for ≥12 months both prior to and following the index date. Serious infections and cardiovascular complications requiring hospitalization (diagnosis code in any position) and associated inpatient costs were evaluated during a fixed 12-month follow-up period. Statistical differences in outcome distributions and costs (reported per patient per month [PPPM]) between the groups were tested. Results: Of 1,948 iNHL patients, 147 had IM and 1,058 had BR as index therapy with ≥12 months of follow-up data. Patients receiving IM were older, more often male, and more likely to have had a lower respiratory tract infection (LRTI) or atrial fibrillation (AF) during baseline compared to BR patients, otherwise the groups had similar baseline characteristics. Hospitalization for serious infections was similar for IM and BR patients during the follow-up period (17.0% vs. 14.4%; p = 0.397); among hospitalized patients, the IM and BR groups incurred similar PPPM inpatient costs ($2,839 vs. $3,954; p = 0.188). Specifically, 7.5% of IM patients had a bacterial infection hospitalization and incurred $2,561 PPPM vs 7.6% of BR patients who incurred $3,975 PPPM (both p > 0.05); 8.8% of IM patients had a LRTI hospitalization and incurred $3,629 PPPM vs 6.1% of BR patients who incurred $4,980 PPPM (both p > 0.05). Hospitalization for cardiovascular complications was similar during follow-up for IM and BR patients (15.6% vs. 12.2%; p = 0.237); among hospitalized patients, the IM and BR groups incurred similar PPPM costs ($3,777 vs. $3,862; p = 0.948). Specifically, 7.5% of IM patients had a hospitalization for AF and incurred $4,481 PPPM vs 3.6% of BR patients who incurred $4,860 PPPM (p = 0.025 and p = 0.875, respectively). Conclusions: In a real-world setting, serious infections and cardiovascular complications requiring hospitalization, including associated costs, were similar among iNHL patients treated with first-line IM or BR over 12 months, although IM patients were more likely to have an AF-related complication.

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Treatment patterns and clinical outcomes of chemotherapy treatment in patients with muscle-invasive or metastatic bladder cancer in the Netherlands

Scientific Reports ◽

10.1038/s41598-020-72820-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Daan J. Reesink ◽

Ewoudt M. W. van de Garde ◽

Bas. J. M. Peters ◽

Paul B. van der Nat ◽

Maartje Los ◽

...

Keyword(s):

Bladder Cancer ◽

Real World ◽

Treatment Patterns ◽

Second Line ◽

Chemotherapy Treatment ◽

First Line ◽

Real World Data ◽

World Data ◽

Metastatic Bladder Cancer ◽

Muscle Invasive

Abstract This retrospective study was performed to evaluate real-world oncological outcomes of patients treated with chemo-based therapy for muscle-invasive or metastatic bladder cancer (MIBC/mBC) and compare results to data from RCTs and other cohorts. Among 1578 patients diagnosed, 470 (30%) had MIBC/mBC. Median overall survival (mOS) for RC alone (47 months), first-line (13 months) and second-line (7 months) chemotherapy, and chemotherapy for recurrent disease (8 months) were similar to literature. Treatment with neoadjuvant and induction chemotherapy (NAIC) was only utilized in 9% of patients, and often in patients with poor disease status, resulting in a lower mOS compared to literature (35 and 20 months, respectively). Patients treated with chemotherapy had many adversities to treatment, with only 50%, 13%, 18% and 7% of patients in NAIC, first-line, salvage after RC, and second-line setting completing the full pre-planned chemotherapy treatment. Real-world data shows NAIC before RC is underutilized. Adversities during chemotherapy treatment are frequent, with many patients requiring dose reduction or early treatment termination, resulting in poor treatment response. Although treatment efficacy between RCTs and real-world patients is quite similar, there are large differences in baseline characteristics and treatment patterns. Possibly, results from retrospective studies on real-world data can deliver missing evidence on efficacy of chemotherapy treatment on older and ‘unfit’ patients.

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Burden of Hospitalizations Due to Epstein-Barr Virus-Driven Post-Transplant Lymphoproliferative Disorder (EBV+PTLD) in Patients Who Failed First Line Rituximab or Rituximab Plus Chemotherapy Following Solid Organ Transplant (Post-SOT): A Retrospective Chart Review Study of German PTLD Registry

Blood ◽

10.1182/blood-2019-124583 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 65-65

Author(s):

Heiner Zimmermann ◽

Hairong Xu ◽

Arie Barlev ◽

Yang Zhang ◽

Dhanalakshmi Thirumalai ◽

...

Keyword(s):

Research Funding ◽

Index Date ◽

Average Length ◽

First Line ◽

Employment Equity ◽

Failure Index ◽

First Line Therapy ◽

Line Therapy ◽

Equity Ownership ◽

The Mean

Background: Post-transplant lymphoproliferative disorder (PTLD) is a rare and often aggressive disease in the setting of immunosuppression following solid organ transplant (post-SOT). About 50% of cases are associated with Epstein-Barr virus (EBV) infection of B cells, either due to reactivation of the virus after transplantation, or from primary EBV infection. Data remain very limited with respect to overall clinical and economic burden among EBV+PTLD patients (pts), particularly in the setting of pts who fail first line therapy. This retrospective chart review aimed to quantify the burden of hospitalization due to EBV+PTLD in post-SOT pts who failed first-line therapy in the real-world setting in Germany. Study Design and Methods: The German PTLD registry database was screened for pts with EBV+PTLD post-SOT who were refractory (failed to achieve complete [CR] or partial remission [PR]) to rituximab or rituximab plus chemotherapy (CT) or relapsed at any point after such therapy between 2000 to 2015. Pts with primary CNS PTLD were excluded. Pts without any outpatient visit or hospitalization record were excluded from the analysis (n of pts=1). Hospitalization data were reviewed by an experienced physician and adjudicated as PTLD relevant; details on diagnoses and procedures performed during hospitalization were collected from the first diagnosis of PTLD to the earliest of the following: death, loss to follow up or end of study period (Sep 1st, 2018). We estimated the mean number of hospitalizations, average length of inpatient stay per admission and the percentages of time spent in the hospital out of the total time following PTLD index date or treatment failure index date. The PTLD index date was defined as the first date of EBV+PTLD diagnosis; and the treatment failure index date was defined as the earliest date of pts who became refractory or relapsed to first-line therapy of rituximab or rituximab plus CT. Results: A total of 35 EBV+PTLD pts were analyzed. All had failed first line rituximab monotherapy. Median follow up time was 24.8 months from the PTLD index date. Median age at PTLD diagnosis was 47 years (range 18-75). Of these, 6 (17.1%) were polymorphic, 21 (60%) were diffuse large B cell lymphoma, 3 (8.6%) were Burkitt lymphoma, and 5 (14.3%) were other B-cell lymphoma. Among the 35 pts, 23 (65.7%) died: 12 from PTLD, 6 treatment-related, 1 from organ failure, and 4 from other causes. The vast majority of pts (29 out of 35) received CHOP-based CT following rituximab failure (2 other CT, 4 did not receive CT). All pts (100%) had at least one inpatient hospitalization after PTLD diagnosis and 16 (45.7%) pts had at least one ICU admission following PTLD index date. The mean number of PTLD hospitalizations following PTLD index date was 4 (SD 3.2, range 1-12) and the mean average length of stay per hospitalization was 23.8 days (SD 22.6, range 2-94). The mean proportion of time spent in the hospital out of total time at risk from PTLD index date was 20.5% (SD 27.6, range 0.1-100) with an average of 9.5% of time spent in the ICU setting during hospitalization stay (SD 22, range 0-99.5). The mean number of PTLD hospitalizations (n of pts=19) following first course CT failure index date was 2.1 (SD 1.9, range 0-7) and the mean average length of stay per hospitalization was 14.8 days (SD 8.6, range 6-31.6). The mean proportion of time spent in the hospital out of total time at risk from CT failure index date was 41.8% (SD 39.6, range 0-100) with an average of 26% time spent in the ICU setting (SD 39, range 0-100). Conclusions: This is the first study to quantify the hospitalization burden directly related to EBV+PTLD post-SOT in Germany. The results show that hospitalization burden in EBV+PTLD post-SOT pts failing first line rituximab monotherapy is substantial accounting for approximately 20% of patient's time after initial diagnosis of PTLD with around 10% spent in the ICU setting. This hospitalization burden is even higher and accounts for over 40% of time in pts after additional treatment failure to first CT with 26% spent in the ICU setting. Disclosures Zimmermann: Roche: Research Funding; Janssen: Other: Travel, accomodations expenses; Atara Biotherapeutics: Other: Travel, accomodations expenses, Research Funding; Celgene: Other: Travel, accomodations expenses. Xu:Atara Biotherapeutics: Employment, Equity Ownership. Barlev:Atara Biotherapeutics: Employment, Equity Ownership. Zhang:Atara Biotherapeutics: Employment, Equity Ownership. Thirumalai:Atara Biotherapeutics: Employment. Watson:Atara Biotherapeutics: Employment, Equity Ownership. Trappe:Atara Biotherapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Other: Congress related travel support; Roche: Consultancy, Honoraria, Other: Congress related travel support, Research Funding; AbbVie: Consultancy, Other: Congress related travel support; Celgene: Other: Congress related travel support.

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