Discordance between Treatment Guideline Recommendations and Real-World Practice in a Group of Large Integrated Delivery Networks for Venous Thromboembolism (VTE) Patients: A Closer Look at VTE Patients with Cancer

Abstract Background: For patients with VTE, current American Society of Hematology (ASH) guideline panel suggests using direct oral anticoagulants (DOACs) over vitamin K antagonists (VKAs) where VKAs are required to be bridged with a parenteral anticoagulant (PAC). For patients with VTE and cancer, current guidelines recommend DOACs over low molecular weight heparin (LMWH) and LMWH over unfractionated heparin (heparin) for the initial treatment of VTE. Limited evidence is available about the patterns of anticoagulant treatment for VTE in routine clinical practice of large healthcare delivery networks in the United States (US) and whether the VTE treatments are aligned with current guidelines. This study aimed to assess real-world anticoagulant treatment patterns among VTE patients using harmonized electronic health record (EHR) data from four Integrated Delivery Networks (IDNs) in the US. Methods: This was a retrospective, longitudinal, multicenter, cohort study using harmonized EHR data from both inpatient and outpatient settings. The study population included adult patients prescribed DOACs, warfarin, and/or PAC therapy as inpatient or outpatient treatment within ≤30 days of VTE diagnosis, between June 2015 through May 2018. Data from the four IDNs was pooled to describe demographic characteristics and treatment patterns among VTE patients overall and by subgroups. Results: A total of 10,527 patients who were treated with OACs after VTE diagnosis were included for analysis. The mean (SD) age was 61.9 (5.98) years, with 46.1% aged 65 or older. More than half (53.2%) were female, and White patients comprised the majority (74.4%), followed by African American patients (22.8%). Obese and morbidly obese patients comprised 39.1% and 16.1% of patients, respectively. Among all VTE patients, warfarin-only (n=3545; 33.7%) was the most commonly used OAC treatment, followed by warfarin + PAC (n=3128; 29.7%), rivaroxaban-only (n=1357; 12.9%), rivaroxaban + PAC (n=853; 8.1%), apixaban + PAC (n=839; 8.0%), apixaban-only (n=762; 7.2%), and Other OAC (n=357; 3.4%) (Table 1). When stratifying VTE patients by age, gender, race and BMI, some variations in OAC treatment were observed. Among both older (≥65 years) and younger (<65 years) patients, warfarin-only was most commonly used, then warfarin + PAC. Warfarin-only was more commonly used among obese (36.3%) and morbidly obese (40.4%) patients than non-obese (29.8%) patients. OAC treatment patterns were generally comparable among men and women. Among White patients, approximately equal proportions of patients received warfarin + PAC (31.9%) and warfarin-only (31.0%). However, among African-American patients, a higher proportion of patients used warfarin-only (40.9%) vs. warfarin + PAC (24.5%). Patterns of anticoagulant treatments including OACs and/or parental anticoagulants among VTE patients with cancer were further analyzed (Figure 1). Among VTE patients with cancer (n=3657), heparin had the highest use (26.7%), then enoxaparin (22.7%); approximately the same proportion of cancer patients received warfarin-only (16.0%) and warfarin + PAC (16.9%). Of DOACs, rivaroxaban-only was the most commonly used treatment (4.9%), then apixaban + PAC (3.5%), and lastly, rivaroxaban + PAC (3.4%) among cancer patients. Conclusion: Current VTE treatment guidelines recommend warfarin to be bridged with PAC, however, warfarin-only therapy remained the most used treatment option followed by warfarin + PAC. While rivaroxaban and apixaban are not required to be bridged with PAC, such practices were observed for a large proportion of apixaban- and rivaroxaban-treated VTE patients. VTE treatment among patients with cancer was not completely aligned with current guidelines, as heparin was more commonly used than LMWH (enoxaparin). Our findings suggest greater efforts are needed to improve anticoagulant treatment practices among VTE patients. Figure 1 Figure 1. Disclosures Dhamane: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Rosenblatt: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Jiang: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Guo: Bristol Myers Squibb: Ended employment in the past 24 months. Dorsch: Agency for Health Research and Quality: Research Funding; National Institutes of Health/National Institute of Aging: Research Funding; American Health Association Health IT Research Network: Research Funding; Janssen Pharmaceuticals: Honoraria; Bristol Myers Squibb/Pfizer: Research Funding; Amgen: Research Funding. Luo: Pfizer Inc: Current Employment, Current equity holder in publicly-traded company.

Download Full-text

To Treat or Not to Treat? Understanding Treatment Patterns in Patients with Lower-Risk Myelofibrosis at the Time of Enrollment in the MOST Study

Blood ◽

10.1182/blood-2020-134958 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 49-51

Author(s):

Rami S. Komrokji ◽

Brady L. Stein ◽

Robyn M. Scherber ◽

Patricia Kalafut ◽

Haobo Ren ◽

...

Keyword(s):

Board Of Directors ◽

Lower Risk ◽

Research Funding ◽

Symptom Burden ◽

Risk Groups ◽

Treatment Patterns ◽

Low Risk ◽

Publicly Traded ◽

Advisory Committees ◽

Therapy Initiation

Background: Myelofibrosis (MF) is a chronic Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) characterized by extramedullary hematopoiesis, bone marrow fibrosis, splenomegaly, constitutional symptoms, and diminished quality of life. Treatment decisions may involve a variety of factors including prognosis and symptomatology. Data regarding real-world disease and demographic factors that contribute to therapy initiation and choice in pts with lower risk MF are limited. This analysis of data from the ongoing Myelofibrosis and Essential Thrombocythemia Observational STudy (MOST; NCT02953704) assessed whether these factors differ for lower risk pts who were treated vs untreated at enrollment. Methods: MOST is a longitudinal, noninterventional, prospective, observational study in pts with MF or essential thrombocythemia enrolled at clinical practices within the US. Pts included in the analysis (≥18 y), had low risk MF by the Dynamic International Prognostic Scoring System (DIPSS; Blood. 2010;115:1703), or intermediate-1 (INT-1) risk by age >65 y alone. Pt data were entered into an electronic case report form during usual-care visits over a planned 36-month observation period. Pt-reported symptom burden was assessed using the MPN-Symptom Assessment Form (MPN-SAF); Total Symptom Score (TSS) was calculated (0 [absent] to 100 [worst imaginable]; J Clin Oncol. 2012;30:4098). Data were analyzed with basic descriptive and inferential statistics. Results: Of 233 pts with MF enrolled at 124 sites between 11/29/2016 and 03/29/2019, 205 were included in this analysis; 28 were excluded for being INT-1 risk for reasons other than age. Of the 205 pts, 85 (41.5%) were low- and 120 (58.5%) were INT-1 risk; 56.5% (48/85) and 59.2% (71/120), respectively, were being treated at enrollment. Pt characteristics are listed in Table 1A. Fewer low- vs INT-1 risk pts were JAK2 V617F or MPL positive, and more were CALR positive. The proportion of pts with palpable splenomegaly was similar for treated low- and INT-1 risk pts. In low risk pts, the proportion of pts with palpable splenomegaly was higher in untreated vs treated pts; whereas, in INT-1 risk pts, the opposite was observed (ie, lower proportion in untreated vs treated pts). Blood counts were generally similar across cohorts, except median leukocytes were lower for low risk treated pts and platelet counts were elevated in low- vs INT-1 risk pts. The proportion of pts with comorbidities was similar across cohorts, except for fewer cardiovascular comorbidities in low- vs INT-1 risk pts. Mean TSS was lower in low- vs INT-1 risk pts, but the proportion of pts with TSS ≥20 was greater in treated vs untreated pts in both low- and INT-1 risk groups. Fatigue was the most severe pt-reported symptom in all cohorts. Differences in mean TSS and individual symptom scores between risk groups were not significant (P > 0.05), except itching was worse among INT-1 risk pts (P=0.03). Physician-reported signs and symptoms were generally more frequent for untreated vs treated pts, irrespective of risk (all P > 0.05). Most low risk (69.4%) and INT-1 risk pts (61.2%) who were currently untreated at enrollment had not received any prior MF-directed treatment (Table 1B); the most common prior treatment among currently untreated pts was hydroxyurea (HU) in both risk groups. Of currently treated pts, HU was the most common MF-directed monotherapy at enrollment in low-risk pts, and ruxolitinib was most common in INT-1 risk pts. No low risk pts and few INT-1 risk pts were currently receiving >1 MF-directed therapy at enrollment. Conclusion: These real-world data from pts with MF enrolled in MOST show that a substantial proportion of both low- and INT-1 risk pts who had received treatment before enrollment were not being treated at the time of enrollment. Although watch-and-wait is a therapeutic option, the finding that many of these lower risk pts had in fact received prior therapies suggests an unmet need for effective and tolerable second-line treatment options. Treated pts had greater pt-reported symptom burden vs untreated pts, which suggests that high symptom burden may contribute to the decision for treatment. Prospective studies are needed to evaluate symptom burden change with therapy initiation. In this regard, future analyses of data from MOST are planned to assess the longitudinal evolution of the clinical characteristics, treatment patterns, and management of pts with MF. Disclosures Komrokji: Geron: Honoraria; Agios: Honoraria, Speakers Bureau; AbbVie: Honoraria; Incyte: Honoraria; Novartis: Honoraria; BMS: Honoraria, Speakers Bureau; JAZZ: Honoraria, Speakers Bureau; Acceleron: Honoraria. Stein:Incyte: Research Funding; Kartos: Other: educational content presented; Constellation Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Pharmaessentia: Membership on an entity's Board of Directors or advisory committees. Scherber:Incyte Corporation: Current Employment, Current equity holder in publicly-traded company. Kalafut:Incyte: Current Employment, Current equity holder in publicly-traded company. Ren:Incyte: Current Employment, Current equity holder in publicly-traded company. Verstovsek:Incyte Corporation: Consultancy, Research Funding; Roche: Research Funding; Genentech: Research Funding; Blueprint Medicines Corp: Research Funding; CTI Biopharma Corp: Research Funding; NS Pharma: Research Funding; ItalPharma: Research Funding; Celgene: Consultancy, Research Funding; Gilead: Research Funding; Protagonist Therapeutics: Research Funding; Novartis: Consultancy, Research Funding; Sierra Oncology: Consultancy, Research Funding; PharmaEssentia: Research Funding; AstraZeneca: Research Funding; Promedior: Research Funding.

Download Full-text

Treatment Patterns and Outcomes of Patients with Double-Class Refractory or Triple-Class Refractory Multiple Myeloma: A Retrospective US Electronic Health Record Database Study

Blood ◽

10.1182/blood-2021-152301 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2705-2705

Author(s):

Feng Wang ◽

Boris Gorsh ◽

Maral DerSarkissian ◽

Prani Paka ◽

Rachel Bhak ◽

...

Keyword(s):

Research Funding ◽

Performance Status ◽

Treatment Patterns ◽

Multiple Drug ◽

Publicly Traded ◽

Analysis Group ◽

Refractory Status ◽

Drug Classes ◽

Immunomodulatory Drug

Abstract Introduction: Patients with relapsed/refractory multiple myeloma (RRMM) resistant to multiple drug classes remain a high unmet need population, despite advances in MM patient care. The objective of this study was to assess real-world treatment patterns and outcomes in patients with RRMM who had failed multiple prior lines of therapy (LOT) and were refractory to multiple drug classes to identify gaps in their treatment pathways. Methods: This longitudinal retrospective cohort study utilized the COTA de-identified real-world database derived from US electronic health records of partnered healthcare providers from Q3 1988 through Q1 2020. Adults with active RRMM previously exposed to a proteasome inhibitor (PI) and an immunomodulatory drug and who received ≥3 prior LOTs were identified. Patients were further categorized as refractory to a PI and an immunomodulatory drug (double-class refractory [DCR]) or additionally to an anti-CD38 monoclonal antibody (i.e. daratumumab; triple-class refractory [TCR]). Determining refractory status was based on International Myeloma Working Group criteria. Index LOT was a new LOT after evidence of DCR or TCR status following ≥3 (DCR) or ≥4 (TCR) prior LOTs. Patient characteristics described included Eastern Cooperative Oncology Group (ECOG) performance status, International Staging System (ISS) stage, cytogenetic risk, age, index date, sex, and follow up time. Treatment pattern assessments included treatments received before/during/after index LOT, reasons for discontinuation, refractory status, and retreatment characteristics. Patient outcomes (overall survival [OS], duration of treatment [DOT], and time to next therapy [TTNT]) were analyzed using Kaplan-Meier survival analysis methods. Results: After excluding patients who were aged <18 years at start of index LOT with no evidence of clinical activity and who participated in a clinical trial during index LOT, 381 (DCR) and 173 (TCR) patients were available for analysis. Median follow-up from index LOT initiation through end of data availability/death was 14 (DCR) and 8 (TCR) months. Demographic characteristics were consistent between DCR and TCR patients. Approximately half were aged ≥65 years (49% DCR; 53% TCR), majority had high-risk cytogenetics (56% DCR; 66% TCR) or prior autologous stem cell transplantation (>62%), and 14-16% had ISS stage III. Patients had a median of 3 (DCR) and 6 (TCR) prior LOTs. Prior to index LOT, bortezomib and lenalidomide were the most commonly received PI and immunomodulatory drug (received by >98% of DCR or TCR patients) and the most common PI and immunomodulatory drugs to which patients were refractory (71% and 84% DCR; 76% and 83% TCR, respectively). At index LOT, PI/immunomodulatory drug-based and daratumumab-based therapies remained the most common therapies. Bortezomib and lenalidomide had the longest time to refractory status and highest retreatment rates among DCR or TCR patients. Approximately 40% of TCR patients were retreated with daratumumab-based therapies after becoming refractory (Table). After index LOT, 70% of DCR and 58% of TCR patients continued to a subsequent LOT. Patients most frequently discontinued index LOT due to disease progression (59% DCR; 60% TCR), toxicity (23% DCR; 25% TCR), or doctor preference (14% DCR; 10% TCR). Median duration of gaps between LOTs generally were shorter than 1 month (Table). Median OS was 22.3 (DCR) and 11.6 (TCR) months. Median DOT was 3.3 (DCR) and 2.8 (TCR) months, and median TTNT was 4.1 (DCR) and 3.2 (TCR) months. In multivariate statistical analyses, inferior baseline ECOG performance scores, and high-risk cytogenetic abnormalities were associated with worse prognosis (higher risk of death, shorter DOT, and shorter TTNT) in DCR and TCR patients. Age was not a significant factor after adjusting for other baseline factors. Conclusions: Treatment options are limited for US patients with DCR and TCR RRMM. DCR and TCR patients were frequently retreated with a PI, an immunomodulatory drug, or daratumumab, despite refractoriness to these agents. Many DCR and TCR MM patients stopped active MM treatment after discontinuing index treatment. Patients with DCR and TCR MM have poor prognosis, especially among high cytogenetic risk and poor performance status patients. This study provides the benchmark for new therapies, like BCMA-targeted agents, to be tested in this population. Funding: GSK (Study 217353). Figure 1 Figure 1. Disclosures Wang: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Gorsh: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. DerSarkissian: Analysis Group, Inc.: Current Employment. Paka: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Bhak: Analysis Group, Inc.: Current Employment; GlaxoSmithKline: Research Funding. Boytsov: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Zichlin: GlaxoSmithKline: Research Funding; Analysis Group, Inc.: Consultancy, Current Employment. Sansbury: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Yee: Analysis Group, Inc.: Current Employment; GlaxoSmithKline: Research Funding. Ferrante: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Khanal: GlaxoSmithKline: Research Funding; Analysis Group, Inc.: Current Employment. Noman: Analysis Group, Inc.: Current Employment; GlaxoSmithKline: Research Funding. Duh: Novartis: Other: I am an employee of Analysis Group, a consulting company that received funding from Novartis for this research study..

Download Full-text

Treatment Patterns and Outcomes of Patients with Newly Diagnosed Acute Myeloid Leukemia (AML) Treated with Hypomethylating Agents (HMA) in the United States (US)

Blood ◽

10.1182/blood-2020-134830 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 14-16

Author(s):

Timothy S. Pardee ◽

Jessica Oschwald ◽

Esprit Ma ◽

Tao Xu ◽

Melissa Montez ◽

...

Keyword(s):

Clinical Practice ◽

Research Funding ◽

Community Setting ◽

Patient Characteristics ◽

Treatment Patterns ◽

Survival Outcomes ◽

Newly Diagnosed ◽

Publicly Traded ◽

The Past ◽

The Us

Introduction: AML is an aggressive disease with poor prognosis that predominantly affects older adults. Due to advanced age and associated comorbidities, many patients are not fit for intensive induction chemotherapy. Monotherapy with HMAs such as azacitidine (AZA) or decitabine (DEC) is often still considered as standard of care for these patients, despite mixed evidence from studies regarding the benefit of HMAs alone (Duchmann & Itzykson. Int J Hematol 2019). The aim of the current study is to evaluate patient characteristics, treatment patterns and outcomes of patients with AML treated with HMA monotherapy as first line (1L) in clinical practice in the US. Methods: This is a retrospective observational study of the Flatiron Health database; a nationwide, longitudinal, demographically and geographically diverse database representing more than 2.4 million patients with cancer in the US. The database contains de-identified data derived from electronic health records from over 280 cancer clinics, which are predominantly community oncology practices. Patients ≥18 years, diagnosed with AML between 1/1/2014 and 3/30/2020 (excluding acute promyelocytic leukemia and clinical trial enrollment), and who received HMAs as 1L treatment ≤30 days from AML diagnosis were evaluated. Descriptive analyses were conducted on patient characteristics and treatment patterns. Kaplan-Meier analyses were used to estimate time to last administration (TTLA; from initiation to last observed administration before death, end of follow-up or a gap of 60 days) and median overall survival (OS). Results: A total of 2589 patients with an AML diagnosis were included for analysis, where 574 (22%) were treated with 1L HMAs (AZA: n=341 [59%]; DEC: n=233 [41%]). The median age of 1L HMA patients was 79 years with 63% male. Most patients were treated in the community setting (n=511 [89%]; median age: 79 years); those treated in academic centers were slightly younger (n=63 [11%]; median age: 77 years). Characteristics for non-antecedent hematological disorder (AHD)-AML (n=327) and AHD-AML (n=247) patients are presented in Table 1. Median TTLA with 1L HMA was 77 days with a median of 3 cycles of both AZA and DEC. Of the 168 patients who received second-line (2L) therapy, 82% (n=138) received another low-intensity therapy or combination (of which only 14 received targeted therapies) (Figure 1). Overall, 44% of 1L HMA patients (n=254) had evidence of molecular testing before 1L treatment initiation (this was more common in later years). Of the 228 patients tested for FLT3, 30 (13%) were FLT3 positive; 7 (23%) FLT3-positive patients were treated with 2L or third-line (3L) FLT3-targeted therapies (gilteritinib, midostaurin or sorafenib). Of the 152 patients tested for IDH1/2, 35 (23%) were IDH1/2 positive; 5 (14%) IDH1/2-positive patients were treated with 2L or 3L targeted agents (enasidenib or ivosidenib). A median OS of 6.3 months (95% CI: 5.5-7.5) was observed in the overall 1L HMA cohort. Median OS in 1L HMA patients did not differ with respect to different types of AML (non-AHD-AML: 6.6 [95% CI: 5.5-7.9] months; AHD-AML: 6.0 [95% CI: 4.8-7.5] months, p=0.34) or practice setting (community: 6.0 [95% CI: 5.3-7.0] months; academic: 8.3 [95% CI: 6.9-13.3] months, p=0.14). One-year OS was 31.4% and 30.1% for non-AHD-AML and AHD-AML patients, respectively. Patients treated in the community setting had numerically lower 1-year OS (29.7% [95% CI: 25.8-34.3]) than those treated in the academic setting (39.5% [95% CI: 28.6-54.6]), which reflects the higher rates of 2L treatment in academic practice, though this analysis is unadjusted. Conclusions: This new database enabled a detailed analysis of 1L HMA-treated patients with newly diagnosed AML in routine clinical practice predominantly in the community setting. 1L HMA patients have poor survival outcomes (median OS 6.3 months) which are comparable to other real-world data from SEER-Medicare (Zeidan et al. Blood Adv 2020; median OS 7-8 months; median age: 77 years); but shorter than the median OS of 9-10 months observed in 1L HMA-treated AML patients in clinical trials (DiNardo et al. EHA 2020). Limitations of the study included limited conduct of bone marrow biopsies for response and lack of transfusion data. The observed survival outcomes highlight the importance of further treatment advances to address the unmet need in older patients with AML ineligible for intensive induction chemotherapy. Disclosures Pardee: Rafael: Research Funding; Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Pharmacyclics: Speakers Bureau; Rafael Pharmaceuticals: Consultancy; BMS: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy; Genentech, Inc.: Consultancy; Karyopharm: Research Funding. Oschwald:Roche Products Limited: Current Employment. Ma:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company. 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.. Montez:F. Hoffmann-La Roche: Current equity holder in publicly-traded company; Genentech, Inc.: Current Employment. Ramsingh:Genentech, Inc.: Current Employment; NEKTAR: Current equity holder in publicly-traded company; Exelixis: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months, Ended employment in the past 24 months; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Hong:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. Choi:AbbVie: Current Employment, Current equity holder in publicly-traded company. Flahavan:Roche Products Ltd.: Current Employment; F. Hoffmann-La Roche: Current equity holder in publicly-traded company. OffLabel Disclosure: Discussion will include the use of decitabine for the treatment of AML.

Download Full-text

Real-World Assessment of Prior Treatment Patterns in Patients Receiving Belantamab Mafodotin Using a Longitudinal Pharmacy and Medical Open Source Claims Database

Blood ◽

10.1182/blood-2021-152242 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4973-4973

Author(s):

Natalie Boytsov ◽

Karen Stockl ◽

Chi-Chang Chen ◽

Feng Wang ◽

Xin Wang ◽

...

Keyword(s):

Open Source ◽

Treatment Period ◽

Real World ◽

Research Funding ◽

Median Number ◽

Treatment Patterns ◽

Prior Treatment ◽

Immunomodulatory Drugs ◽

Publicly Traded ◽

Patient Demographics

Abstract Introduction: Belantamab mafodotin (belamaf) is a first-in-class B-cell maturation antigen-targeting antibody-drug conjugate, with a manageable adverse event profile, that has shown durable efficacy in a broad range of patients with relapsed or refractory multiple myeloma (RRMM) (Lonial et al., Lancet Oncol. 2020). As belamaf is an approved therapy, it is important to understand how it is being integrated into the management of patients with RRMM. The aim of this analysis was to examine baseline demographic and treatment patterns of these patients prior to belamaf in a real-world clinical practice. Methods: This descriptive, retrospective cohort study used IQVIA's longitudinal pharmacy and medical open source claims database, a nationally representative real-world database. The study covered the period from January 2001 to April 2021. Patient inclusion into the study required belamaf treatment initiation and ≥18 years of age at initiation. The first claim date for belamaf during the index period (August 2020 to April 2021) was the index date (ID). Key measures included patient demographics and prior MM treatments. Patient demographics were identified at the ID. Prior MM treatments were assessed during the prior treatment period, which extended from the database start date (January 2001) until the ID. The definition of a line of therapy (LOT) used in this analysis was consistent with published guidance (Rajkumar SV, et al. Blood, 2015;126:921-922). Treatments of interest were identified within the first 28 days of the first observed claim for MM treatment. A new LOT was identified if a new treatment was added after the initial 28 days after the start of the LOT, ≥1 treatment was discontinued (defined by a coverage gap >60 days), or the same LOT was restarted at a later date if ≥1 regimen was administered in between. Different therapeutic classes (e.g. PIs, immunomodulatory drugs, anti-CD38 antibodies) could be used in each LOT either singly or in combinations. Addition/deletion of corticosteriods did not constitute a new LOT. Results: 304 patients with a claim for belamaf were identified in the database and included in the analysis; median age was 70 years and 50.3% were female. Median (range) time from the earliest observed claim for MM treatment during the prior treatment period to the ID was 1,812 (104─6,676) days. Median (range) time from the earliest observed diagnosis for MM during the prior treatment period to the ID was 2,123 (22-7,186) days (~5.8 years). The median number of MM therapeutic classes, overall, received during the prior treatment period was 5; 82.9% of patients with MM received ≥4 classes of MM therapy. Prior therapy for MM was observed for 303 patients; the therapeutic classes of those MM treatments are shown in the Table. The median number of observed LOTs received by patients in the prior treatment period was 5 and 73.0% had ≥4 LOTs. LOT for belamaf may be over/under estimated as reporting on some of the MM medications was embargoed by manufacturers and/or specialty pharmacies for certain periods of time, leading to some incompleteness of data. Embargoed products included lenalidomide, pomalidomide, selinexor, thalidomide, ixazomib, and bortezomib. Although data capture for these MM treatments may not be complete in open source claims, some of the claims data for these medications were included in this analysis, i.e., medical claims for infused medications and pharmacy claims from switch suppliers for oral medications. Conclusions: The real-world evidence analyzed in this study is in line with the baseline characteristics reported for the DREAMM-1 and DREAMM-2 trials (Lonial et al., Lancet Oncol. 2020, Trudel et al., Blood Cancer J., 2019). Patients receiving belamaf have triple-class refractory myeloma with multiple LOTs generally aligned with the current indication. The most frequent prior treatments included proteasome inhibitors, anti-CD38 monoclonal antibodies, immunomodulatory drugs, and corticosteroids. Corticosteroid use is high as it is required to be prescribed in combination with other drugs according to their indications. This study identified patients in the US receiving belamaf and provides early insights into the patient demographic and clinical characteristics as well as number and range of treatments prior to treatment with belamaf. Funding: GSK (Study 214283). Figure 1 Figure 1. Disclosures Boytsov: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Stockl: IQVIA: Current Employment; GlaxoSmithKline: Research Funding. Chen: GlaxoSmithKline: Research Funding; IQVIA: Current Employment. Wang: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Wang: IQVIA: Current Employment; GlaxoSmithKline: Research Funding. Cao: IQVIA: Current Employment. Doherty: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company. Paka: GlaxoSmithKline: Current Employment, Current equity holder in publicly-traded company.

Download Full-text

Real-World Treatment Patterns and Outcomes of Patients with Chronic Lymphocytic Leukemia (CLL) Receiving First-Line (1L) Therapy in the United States (US)

Blood ◽

10.1182/blood-2021-148472 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4086-4086

Author(s):

Anthony R. Mato ◽

Arliene Ravelo ◽

Tu My To ◽

Robert Schuldt ◽

Juliana M.L. Biondo

Keyword(s):

High Risk ◽

Research Funding ◽

Treatment Patterns ◽

Publicly Traded ◽

Treatment Regimens ◽

The Past ◽

Oral Agents ◽

The Us ◽

Testing Patterns ◽

Over Time

Abstract Background: There have been many advances in CLL treatments over the past decade, with a number of novel agents targeting molecular pathways within CLL cells receiving approval from the US Food and Drug Administration. Here, we assessed the evolution of molecular testing patterns, treatment patterns, and clinical outcomes over time in patients receiving 1L CLL treatment in a real-world US database. Methods: This was a retrospective cohort study using the Flatiron Health database, a longitudinal database comprising de-identified, patient-level, structured and unstructured data, curated via technology-enabled abstraction. During the study period, the de-identified data originated from approximately 280 cancer clinics (~800 sites of care) in the US. Patients aged 18 years and older who were diagnosed with CLL and initiated 1L treatment between December 2015 and December 2020 were selected. Participants who took part in a clinical trial in any line of therapy, or who had any other primary cancer diagnosis, were excluded. Baseline characteristics, including testing patterns, at initiation of 1L treatment were assessed using descriptive statistics. Treatment patterns and outcomes, such as time to next treatment or death (TTNTD), were analyzed. Kaplan-Meier analysis was used to estimate TTNTD. Results: Among 3654 patients with treatment-naive CLL who were selected from the de-identified database, the mean age at 1L treatment initiation was 70 years (range, 29-85); 64.3% of patients were male; 72.1% were White, 8.2% Black, 3.9% Hispanic/Latino, 1.0% Asian, and 14.9% were of other ethnicity/race. Approximately one-third (34.7%) of patients had Rai stage 0-I disease, 6.9% had stage II, 6.3% stage III, 11.5% stage IV, and 40.6% had undocumented Rai stage. Testing patterns: The majority of identified patients (3202/3654; 87.6%) had undergone cytogenetic testing, fluorescence in situ hybridization, or IGHV mutation testing. Compared with 2015-2016, testing rates were higher in 2019-2020 for chromosome 17p deletion (del(17p); 36.1% vs 45.7%, respectively; p<0.001) and for IGHV mutation status (84.7% vs 89.2%, respectively; p=0.003). Overall, 11.0% of patients had del(17p). Of those tested for IGHV (1472/3654; 40.3%), 58.3% had unmutated IGHV. Treatment patterns: The 10 most commonly used 1L CLL treatments, which overall represented 91.8% of all 1L treatments, and their evolution over time, are reported in Table 1. Of the patients receiving these top 10 1L treatment regimens overall, 45.7% received regimens including novel targeted oral agents, 33.4% received chemo-immunotherapy (CIT), and 19.7% received anti-CD20 monotherapy. Evaluation of each 2-year period shows that treatment patterns for the top 10 1L treatment regimens shifted, with use of novel targeted oral agents increasing from 27.1% (2015-2016) to 63.8% (2019-2020) (p<0.001), while use of CIT and chemotherapy decreased over time (Table 2). Approximately 30.0% (1088/3654) of 1L-treated patients went on to receive second-line treatments. Outcomes: Median TTNTD was 34.4 months for all patients receiving 1L CLL treatment, and 36.5 months for patients who received the 10 most common 1L treatments across the 6-year study period (n=3360). Median TTNTD was 47.0 months for patients who received novel targeted oral agents and 41.5 months for patients who received CIT (unadjusted p=0.16). When evaluating outcomes in patients with high-risk cytogenetics, median TTNTD was 29.1 months for patients with del(17p) and 37.2 months for those with unmutated IGHV, but was longer in those patients who received treatment with novel targeted oral agents (median TTNTD of 43.9 and 46.7 months, respectively; Table 3). Conclusions: This analysis provides the current state of 1L CLL testing and treatment patterns and outcomes in the US from 2015 to 2020. As expected, the use of novel targeted oral agents increased over time, with a corresponding increase in TTNTD. Clinical outcomes were improved in patients receiving novel targeted oral agents, both overall and in high-risk subgroups. Following on from this, a comparative study of TTNTD for novel oral agents versus CIT, and analyses of outcomes of different sequencing of therapies, will be conducted. Figure 1 Figure 1. Disclosures Mato: Nurix: Research Funding; Johnson and Johnson: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Acerta/AstraZeneca: Consultancy, Research Funding; DTRM BioPharma: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; MSKCC: Current Employment; Sunesis: Consultancy, Research Funding; AstraZeneca: Consultancy; TG Therapeutics: Consultancy, Other: DSMB, Research Funding; Genmab: Research Funding; LOXO: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ravelo: Genentech, Inc.: Current Employment; Roche Holdings: Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. To: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Schuldt: Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company; Johnson & Johnson: Divested equity in a private or publicly-traded company in the past 24 months. Biondo: Genentech, Inc.: Current Employment; Roche: Current holder of individual stocks in a privately-held company.

Download Full-text

Analysis of Hemophilia a Outcomes and Treatment Patterns Using Real-World Data from the Canadian Hemophilia Bleeding Disorder Registry

Blood ◽

10.1182/blood-2020-137320 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 37-38

Author(s):

Adrienne Lee ◽

Federico Germini ◽

Man-Chiu Poon ◽

Arun Keepanasseril ◽

Quazi Ibrahim ◽

...

Keyword(s):

Research Funding ◽

Hemophilia A ◽

Data Entry ◽

Treatment Patterns ◽

Advisory Board ◽

Third Party ◽

Bleeding Disorders ◽

Board Meeting ◽

Publicly Traded ◽

High Responders

BACKGROUND: The Canadian Hemophilia Bleeding Disorders Registry (CBDR) is a clinical database for patients in Canada with bleeding disorders. It was launched on July 1, 2015 and is used by all Canadian Hemophilia Treatment Centers (HTCs) to assist in managing the treatment of hemophilia and other bleeding disorders. CBDR integrates with the patient data entry platform, myCBDR, allowing direct acquisition of infusions, bleeding events, and other patient reported outcome (PRO) data. In August 2018, Emicizumab was approved by Health Canada and made available for the treatment of persons with hemophilia A (PwHA) with inhibitors, and to a small number of PwHA without inhibitors via compassionate access beginning November 2019. With the anticipated change in treatment patterns, disease outcomes, and unique safety consideration (e.g. thrombotic events) with use of Emicizumab, we aim to use CBDR data to describe the current demographics, outcomes, and treatment patterns of hemophilia A patients in Canada before emicizumab. This analysis will provide evidence for and inform on the feasibility and data quality/completeness of the CBDR database to assess the impact of Emicizumab on hemophilia outcomes. METHODS: De-identified data was extracted from the CBDR database for all registered hemophilia A patients who had not received Emicizumab between January 2018 and December 2019. Data is presented in aggregate as mean ± SD, median [IQR] or frequency (%). Annual bleeding rates (ABR) and annual joint bleeding rates (AJBR) were calculated as (total number of bleeds/ duration of follow-up)*365.25 for each patient with at least one treated bleed. Treatment plans during the 2-year period were defined following a two-step operationalization prioritizing ITI and prophylaxis. Treatment groups are not mutually exclusive as one patient may have used more than one treatment plan over the 2-year study duration. This study received research ethics board approval and abides by the guiding principles of the Declaration of Helsinki. RESULTS: We identified 2525 PwHA registered in CBDR who had not received Emicizumab during the study period. Demographic characteristics, inhibitor status, and treatments are found in Table 1. Mean(±SD) age for the entire cohort was 36.7±21.5 years with 23.2% ≤ 18 years. Inhibitor status was missing in 47.5%. In those with inhibitor status available, 3.8% (50/1326) have FVIII inhibitor present [Low responders 66% (33/50), High responders 34% (17/50)], 17.8% (236/1326) had a history of FVIII inhibitors, and 78.4% (1040/1326) have no current or historical inhibitor. Of the high-responders, 29.4% (5/17) received immune tolerance induction (ITI), 52.9% (9/17) received prophylaxis and 52.9% (9/17) received on demand treatment. Median ABR (IQR) [2.8 (1.5, 4.6) vs. 2.0 (1.0, 5.5), p=0.691] and median AJBR (IQR) [2.0 (0.9, 3.0) vs. 1.8 (1.0, 4.5), p=0.669] are slightly higher in PwHA with inhibitor (n=28) compared to PwHA without inhibitor (n=398) (Figure 1A). Median Hemophilia Joint Health Scores (HJHS) were higher in PwHA with inhibitors (n=15) compared to PwHA without inhibitor (n=232) [5.5 (0.0, 34.0) vs.3.0 (0,16), p=0.781] (Figure 1B). However, the tests werenumbers are not sufficiently powered due to fewer number of observations, highlighting the importance of up-to-date and complete record entry. CONCLUSION: This analysis confirms the feasibility of using de-identified data extracted from the CBDR database to provide a snapshot of the PwHA demographics, treatments, bleeding, and joint status outcomes over a defined period (i.e. before starting Emicizumab). Incomplete data reporting accounts for missing inhibitor status, so interpretation must be done cautiously and account for data gaps. Encouraging complete and up-to-date data entry will be important for maintaining data quality and accuracy. As more Canadian PwHA switch to Emicizumab, CBDR will allow us to compare treatment patterns and patient outcomes before and after starting Emicizumab. This will inform hemophilia treaters and regulatory authorities of the real-world safety and efficacy outcomes of Emicizumab in PwHA with and without inhibitors. Disclosures Lee: Bayer: Honoraria; Takeda: Consultancy, Honoraria, Speakers Bureau. Germini:Bayer: Research Funding; NovoNordisk: Research Funding; Roche: Research Funding; Takeda: Research Funding. Poon:Pfizer: Other: honoraria for advisory board meeting attendance; CSL-Behring: Other: honoraria for advisory board meeting attendance, Research Funding; Bioverative/Sanofi: Other: honoraria for advisory board meeting attendance; Bayer: Other: honoraria for advisory board meeting attendance, Research Funding; Roche: Other: honoraria for advisory board meeting attendance; Novo Nordisk: Other: honoraria for advisory board meeting attendance; Takeda: Other: honoraria for advisory board meeting attendance. Shang:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Nissen:F. Hoffmann-La Roche Ltd: Current Employment; GSK: Research Funding; Novartis: Research Funding; Actelion: Consultancy. Meier:F. Hoffmann-La Roche Ltd: Current Employment, Current equity holder in publicly-traded company. Sima:F. Hoffmann-La Roche Ltd/Genentech: Current Employment, Current equity holder in publicly-traded company, Other: All authors received support for third party writing assistance, furnished by Scott Battle, PhD, provided by F. Hoffmann-La Roche, Basel, Switzerland.. Matino:Sobi: Honoraria; Pfizer: Honoraria, Research Funding; Bioverativ: Honoraria; Sigilon: Honoraria. Iorio:Sanofi: Research Funding; Roche: Research Funding; Pfizer: Research Funding; Octapharma: Research Funding; NovoNordisk: Research Funding; BioMarin: Research Funding; Bayer: Research Funding; Spark: Research Funding; Takeda: Research Funding; Uniqure: Research Funding; Freeline: Research Funding; CSL: Research Funding; Grifols: Research Funding.

Download Full-text

Lines of Therapy in Patients with Relapsed or Refractory Large B-Cell Lymphoma and Stem Cell Transplant-Intended Treatment

Blood ◽

10.1182/blood-2020-134808 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 45-46

Author(s):

Julia Thornton Snider ◽

Paul Cheng ◽

Xue Song ◽

Donna McMorrow ◽

David Diakun

Keyword(s):

Research Funding ◽

Index Date ◽

Intensive Therapy ◽

B Cell Lymphoma ◽

Treatment Patterns ◽

Cell Transplant ◽

Front Line ◽

Publicly Traded ◽

Line Of Therapy ◽

To Receive

Introduction: Large B-cell lymphoma (LBCL) is the most common subtype of non-Hodgkin lymphoma. Front line therapy is curative in about 60% of patients; however, about 30% of patients relapse and about 10% are refractory. For patients failing the front line, stem cell transplant (SCT) is currently the only curative option in second line of therapy (LOT2). This study examined real-world treatment patterns with curative intent in patients with relapsed or refractory LBCL to understand the unmet medical need in the United States. Methods: This retrospective study used IBM MarketScan® Commercial and Medicare Supplemental Databases. Patients with ≥2 LBCL diagnoses on different days in 1/1/2012 - 3/31/2019 were identified (index date = date of the earliest LBCL diagnosis). Patients who were ≥18 years of age on the index date, had ≥1 claim for any LBCL treatment on or following the index date, ≥6 months of data prior to (baseline) and ≥12 months of data after (follow up period) the index date, and had no baseline LBCL diagnosis were included. Treatment patterns, including lines of therapy (LOT), treatment regimen, duration of LOT and time from the end of a previous LOT to the subsequent LOT, were examined. All patients were required to receive first LOT (LOT1) of R-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone +/- rituximab), EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride +/- rituximab), or regimens with anthracycline. Of those, patients were further required to receive LOT2 with SCT-intended intensive therapy or platinum-based chemotherapy as recommended by the National Comprehensive Cancer Network (NCCN). Patients were intended for SCT if they received an SCT-intended LOT2 regimen or received SCT regardless of LOT2 regimen. SCT was identified from the LOT2 start date to the end of the study period. All analyses were stratified by whether a patient was intended for SCT and by receipt of SCT. Results: A total of 3,443 patients with LBCL received an eligible front-line therapy (mean age 59.2 years, male 56.9%, length of follow up 2.5 years, National Cancer Institute (NCI) adapted Deyo-Charlson comorbidity index 0.83). Top comorbidities were other malignancy (63.3%), diabetes (23.3%), psychiatric disturbance (13.9%), and chronic pulmonary obstructive disease (13.2%). Among the LBCL patients, 564 (16.4%) received LOT2 with 197 (34.9%) patients SCT-intended and 367 (65.1%) not SCT-intended (Figure 1). SCT-intended patients were significantly younger than SCT-non-intended patients (55.9 vs. 60.9 years, p<0.001), and patients who received SCT were younger than those who did not receive SCT (53.6 vs. 59.7 years, p<0.001). Among the 197 patients intended for SCT, only 55.3% (n=109/197) received NCCN recommended LOT2 for intensive therapy: ICE (ifosfamide, carboplatin, etoposide) +/- rituximab (32.5%) and GemOx (gemcitabine, oxaliplatin) +/- rituximab (19.3%) were the most common regimens. SCT-intended patients initiated LOT2 nearly one year (345 days) after and third line of therapy (LOT3) 501 days after their LBCL index diagnosis (Figure 2). Duration of LOT decreased as patients moved on to later LOTs (LOT1=121 [standard deviation (SD)=69], LOT2=89 [SD=145] and LOT3=46 [SD=23] days). Likewise, the time between 2 consecutive LOTs decreased (194 [SD=258] days between end of LOT1 and start of LOT2, 124 [SD=182] days between end of LOT2 and start of LOT3). Steroids were often prescribed during LOT1 (82.2%) and LOT2 (74.6%) as concomitant therapy. Among the 109 patients receiving SCT-intended regimens, only 34 (31.2%) went on to receive SCT. An additional 88 patients received SCT without being observed to receive an SCT-intended regimen. They might have received therapy in the inpatient setting, which could not be captured in claims data. Among the 82 patients with LOT3, 60.1% received SCT and 9.8% received Chimeric antigen receptor (CAR) T cell therapy. Conclusion: The findings provide insight into real-world treatment patterns in patients with LBCL who received SCT-intended therapy. A small proportion of LBCL patients received NCCN recommended SCT-preparative regimens in LOT2 and only 31% of them received SCT. This highlights the magnitude of unmet need for relapsed or refractory LBCL patients. Future studies should examine the impact of new therapies on the management of LBCL. Disclosures Thornton Snider: Kite, A Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company, Research Funding; Precision Medicine Group: Ended employment in the past 24 months, Research Funding. Cheng:Kite, A Gilead Company: Current Employment, Current equity holder in publicly-traded company. Song:IBM Watson Health: Research Funding. McMorrow:IBM Watson Health: Current Employment. Diakun:IBM Watson Health: Current Employment, Research Funding.

Download Full-text

Real World Prospective Observational Multicenter Trial of Venetoclax-Based Therapy for Patients with AML Reveals Unique Patterns of Patient Selection and Treatment Utilization - Revive Study

Blood ◽

10.1182/blood-2021-147245 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1246-1246

Author(s):

Ofir Wolach ◽

Itai Levi ◽

David Lavie ◽

Jonathan Canaani ◽

Sigal Tavor ◽

...

Keyword(s):

Board Of Directors ◽

Patient Selection ◽

Real World ◽

Research Funding ◽

Early Death ◽

Treatment Patterns ◽

Publicly Traded ◽

Advisory Committees ◽

Related Factors

Abstract Background: Venetoclax-based combinations were recently approved to treat patients (pts) with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. Limited prospective 'real-world' data is available on treatment patterns of venetoclax-based therapy in routine clinical practice. We investigated patterns of patient selection, efficacy, toxicity, patient related outcome and post-remission management in a nationwide multicenter prospective observational trial. Methods: Newly diagnosed pts with AML were enrolled at the time of venetoclax-based therapy initiation from 10 medical centers in Israel. Demographic, clinical and patient-related baseline characteristics were documented. Treatment patterns, safety and efficacy outcomes are reported. Results: Between August 12, 2019, and June 17, 2021(data cut) ,127 AML pts were enrolled to receive venetoclax based therapy. Baseline patient and disease characteristics are reported in Table 1. The main reasons for physician's choice of venetoclax-based therapy were age ≥75, comorbidities and ECOG ≥2 (patient related factors) in 76% of cases and adverse disease biology predicting poor response to intensive chemotherapy (disease related factors) in 24% of cases. Most pts started therapy in an inpatient setting, 82 (64.6%) with a median hospitalization duration of 14 days, while 44 pts (34.6%) started therapy as out pts. Pts received a median of 3.8 cycles of therapy (range 1-21). Most pts (97%) received venetoclax in combination with hypomethylating agents. The full dose of 400mg QD after a median ramp-up duration of 3 days was achieved in 88% of the pts. Dose interruptions and dose modifications during follow-up occurred in 59 (46%) and 30 (24%) of pts, respectively. To allow for adequate follow up for response assessment, efficacy analysis was limited to pts enrolled prior to December 31, 2020, and included 108 pts with a median follow-up of 8 months (range 1-20). As of data cut, 93 pts completed cycle 1 of therapy, 66 pts completed cycle 3 and 39 pts completed cycle 6. 29 pts (27%) are still active on treatment. Best composite complete remission [CCR = complete remission (CR) plus CR with incomplete count recovery (CRi)] was achieved in 62 (57%) pts. CCR rates were assessed in different pre-defined subgroups. Best CCR in pts selected for therapy based on disease-related and patient-related factors were 70% and 54% respectively. Best CCR in pts with AML arising from MPN and pts with other AML were 45% and 58% respectively. Estimated median overall survival (OS) of all pts was 9.6 months (range 7.4-10.6) (Figure 1). Achieving CCR was associated with a superior probability for survival. Estimated median OS was 13.6 months (range 10.6 - not reached) in pts achieving CCR and 4.2 months (range 1.2-10.3) in non-CCR (p<.0001). Of responding pts (CR/CRi, partial remission (PR), morphologic leukemia free state (MLFS), 27 (37%) progressed. Estimated median time to progression was 9.2 months (6.7-NR). Allogeneic transplantation following venetoclax based treatment was offered to 16 (26%) pts with a median age of 71 years (range 43-77). Last documented response prior to transplant was CR in 5 (32%) pts, CRi 9 (56%), MLFS 1 (6%) and PR in 1 (6%) patient. Among grade ≥3 AEs were febrile neutropenia in 28% and infections in 21% of pts. Clinical and laboratory tumor lysis syndrome (TLS) was documented in 2 and 4 pts, respectively. Antifungal prophylaxis was administered in 20% of pts and granulocyte colony-stimulating factor (GCSF) support was used in 17% of pts in response. Early death rate at 30 and 60 days were 7% and 13%, respectively. Conclusion: This prospective real-world analysis reveals unique patterns of patient selection and venetoclax treatment utilization in a medical system with wide access for this indication. Venetoclax-based therapies are effective and associated with manageable toxicity, including in AML patient populations that were excluded from previous registration trials with comparable CCR and early death rates. Factors associated with patient selection in the 'real-world' setting and immature follow up data most probably led to a shorter estimated median OS in this analysis as compared to controlled trials. The REVIVE study continues to expand and is expected to provide additional insights on treatment patterns, management as well as clinical and patient related outcomes. Figure 1 Figure 1. Disclosures Wolach: Janssen: Consultancy; Novartis: Consultancy; Amgen: Research Funding; Astellas: Consultancy; Abbvie: Consultancy, Honoraria, Research Funding; Neopharm: Consultancy. Levi: AbbVie: Consultancy, Research Funding. Lavie: AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures; BMS: Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Other: Fees for lectures; Roche: Other: Fees for lectures; Novartis: Other: Fees for lectures. Tavor: AbbVie: Consultancy. Hellmann: AbbVie: Consultancy. Tadmor: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Zuckerman: Gilead Sciences: Honoraria, Speakers Bureau; Novartis: Honoraria; Janssen: Honoraria; Cellect Biotechnology: Honoraria; BioSight Ltd: Honoraria; AbbVie: Honoraria; Orgenesis Inc.: Honoraria. Stemer: AbbVie: Consultancy. Berelovich: AbbVie: Current Employment, Current equity holder in publicly-traded company. Ofek: AbbVie: Current Employment, Current equity holder in publicly-traded company. Frankel: AbbVie: Current Employment, Current equity holder in publicly-traded company. Grunspan: AbbVie: Current Employment, Other: May hold equity. Ofran: Medison Israel: Consultancy; Pfizer: Consultancy; Astellas: Consultancy; AbbVie: Consultancy; Janssen: Consultancy. Moshe: Novartis: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; Astellas: Membership on an entity's Board of Directors or advisory committees, Other: Lectures; AbbVie: Membership on an entity's Board of Directors or advisory committees, Other: Lectures.

Download Full-text

Real-World Treatment Patterns and Healthcare Resource Utilization (HRU) of Patients (Pts) with Paroxysmal Nocturnal Hemoglobinuria (PNH) Receiving Eculizumab in a US Population

Blood ◽

10.1182/blood-2020-141648 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 15-16

Author(s):

Wendy Y Cheng ◽

Sujata P. Sarda ◽

Nikita Mody-Patel ◽

Sangeeta Krishnan ◽

Mihran Yenikomshian ◽

...

Keyword(s):

Blood Transfusion ◽

Research Funding ◽

Index Date ◽

Standard Of Care ◽

Baseline Period ◽

Treatment Patterns ◽

Blood Transfusions ◽

Publicly Traded ◽

Full Cohort ◽

Observation Period

INTRODUCTION The C5 inhibitor eculizumab is the current standard of care for the treatment of PNH. However, some pts receiving eculizumab to treat PNH continue to experience ongoing hemolysis and anemia, resulting in red blood cell transfusion dependence, substantial unmet clinical needs, and considerable health economic burden. This study evaluated the treatment patterns of pts with PNH receiving eculizumab and compared HRU among blood transfusion-dependent (TD) pts versus blood transfusion-free (TF) pts in real-world clinical practice in the United States. METHODS Pts aged ≥12 years with ≥2 claims for eculizumab infusion between April 1, 2014, and September 30, 2019, were identified from the IBM® MarketScan® Research Databases. The index date was the first observed claim for eculizumab infusion with ≥3 months of continuous eligibility prior (baseline period). Pts with ≥1 diagnosis of indications other than PNH for eculizumab (ie, atypical hemolytic uremic syndrome, generalized myasthenia gravis, neuromyelitis optica spectrum disorder) during the baseline period or on the index date were excluded to identify pts with PNH. The full cohort of PNH pts treated with eculizumab were then stratified into the TD cohort (≥1 claim for blood transfusion within 6 months following any eculizumab infusion) or TF cohort. Patient demographic and clinical characteristics in the baseline period were compared between TD and TF cohorts using standardized differences (std diff), with >20% indicating substantial differences. Treatment patterns and HRU (all-cause and PNH-related) were evaluated during the observation period (ie, from index date to earliest date between end of continuous healthcare plan enrollment and end of data availability). Time from index date to treatment discontinuation among pts in the full cohort was assessed using Kaplan-Meier analysis. HRU was compared between TD and TF cohorts using incidence rate ratios (IRRs) adjusted for baseline covariates. RESULTS A total of 151 eculizumab users with PNH were identified as the full cohort; 55 (36%) were TD and 96 (64%) were TF. Mean (range) age was 36.7 (12-74) years among all pts (TD: 35.1 years; TF: 37.6 years). Overall, 56% of pts were female, with a higher proportion in the TD vs TF cohort (67% vs 49%; std diff = 38%). More pts in the TD vs TF cohort had blood transfusions (71% vs 18%; std diff = 127%) and use of corticosteroid therapy (46% vs 32%; std diff = 27%) during baseline. Baseline coagulopathy and aplastic anemia were more common in the TD vs TF cohort (coagulopathy: 49% vs 30%; std diff = 39%; aplastic anemia: 64% vs 43%; std diff = 43%). Myelodysplastic syndrome was present in 10% of the full cohort (TD: 13%; TF: 8%; std diff = 14%). During a mean observation period of 19 months for the overall sample (TD: 20 months; TF: 19 months), pts had a median (interquartile range) of 8 (3-30) eculizumab infusions (TD: 5 infusions; TF: 8 infusions) during maintenance phase; 29% of pts (TD: 21%; TF: 33%) had on average 14 days between maintenance eculizumab infusions; 61% of pts (TD: 66%; TF: 58%) discontinued eculizumab treatment (ie, gap of >42 days between 2 infusions) and the median time to treatment discontinuation was 254 days (TD: 180 days; TF: 337 days). Mean (range) number of blood transfusions among TD pts was 8.5 (1-54). During the observation period, pts in the TD cohort had 2.95 times more all-cause hospitalizations and 4.58 times more hospitalization days compared to pts in the TF cohort (all P < 0.05). Similar trends were observed for PNH-related hospitalizations. Results for all-cause and PNH-related HRU are presented in the Table. CONCLUSIONS This study demonstrated a considerable economic burden among pts with PNH treated with eculizumab, particularly among pts dependent on blood transfusions. TD eculizumab users comprised >36% of the overall sample, indicating that disease activity may not be well controlled. These pts had >4 times the number of hospitalization days compared to TF pts, emphasizing the substantial unmet clinical need despite treatment with eculizumab. These findings suggest that the current PNH standard of care may be insufficient for TD pts. Based on time between dosing intervals, >70% of PNH pts in this study were not dosed per label, and two-thirds of pts discontinued eculizumab within an average of a 1.5-year timeframe. New therapies are needed to reduce the considerable burden of pts with PNH. Disclosures Cheng: Apellis: Research Funding. Sarda:Apellis: Current Employment, Current equity holder in publicly-traded company. Mody-Patel:Apellis: Current Employment, Current equity holder in publicly-traded company. Krishnan:Apellis: Current Employment, Current equity holder in publicly-traded company. Yenikomshian:Apellis: Research Funding. Scoble:Apellis: Current Employment, Current equity holder in publicly-traded company. Mahendran:Apellis: Research Funding. Lejeune:Apellis: Research Funding. Yu:Apellis: Research Funding. Duh:Apellis: Research Funding; Takeda Oncology: Research Funding; GlaxoSmithKline: Research Funding; AstraZeneca: Research Funding; Blueprint Medicine: Research Funding; Novartis: Research Funding; Shire: Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding.

Download Full-text

An Oncology Simulation Model to Estimate 10-Year Progression-Free Survival and Overall Survival Based on the 5-Year Update from the ECHELON-2 Trial in Frontline Patients with Peripheral T-Cell Lymphoma: A United States Perspective

Blood ◽

10.1182/blood-2021-148004 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2466-2466

Author(s):

John M. Burke ◽

Kristina S. Yu ◽

Uche Mordi ◽

Brian Bloudek ◽

Nicholas Liu ◽

...

Keyword(s):

United States ◽

Overall Survival ◽

Research Funding ◽

Progression Free Survival ◽

Brentuximab Vedotin ◽

Treatment Patterns ◽

Publicly Traded ◽

Free Survival ◽

Number Of Patients

Abstract Objectives Peripheral T-cell lymphomas (PTCLs) are a rare and aggressive type of non-Hodgkin lymphoma (NHL) associated with a poor prognosis. Common frontline (1L) regimens include brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone (A+CHP), and cyclophosphamide, doxorubicin, vincristine, and prednisone with or without the addition of etoposide (CHOP and CHOEP, respectively). Based on the 5-year update of the ECHELON-2 trial, patients with previously untreated CD30-expressing PTCL on A+CHP continued to demonstrate clinically meaningful improvements in progression-free survival (PFS) and overall survival (OS) compared with CHOP. Our objective was to estimate the future number of patients alive and progression free with A+CHP over 10-years, based on the 5-year follow-up results from ECHELON-2. Methods An oncology simulation model, from the United States perspective, was developed with a 1-month cycle length that estimates population-level outcomes of PTCL patients based on disease incidence, treatment patterns, PFS, and OS of commonly used regimens for PTCL. Incidence of PTCL, 19.26 cases per 100,000 persons, was derived using Surveillance, Epidemiology and End Results (SEER) estimates for NHL in 2020 and the estimated proportion of PTCL cases (~4%) within the NHL category, provided by the Lymphoma Research Foundation. To populate the base case model, treatment patterns following 1L utilization of CHOP (65%) and CHOEP (35%) were varied over time and compared to A+CHP (40%). The model also includes a portion of patients in remission in 1L who are eligible to receive transplant therapy. Additional model inputs were derived from: 1) ECHELON-2, with 5-year PFS rates of 51.4% (95% CI 42.8, 59.4) for A+CHP, 43.0% (95% CI 35.8, 50.0) for CHOP, and OS HR 0.72 (95% 0.53, 0.99); 2) published literature to inform PFS for consolidation and subsequent lines of therapy; and 3) expert clinicians' opinion on commonly used regimens for relapsed/refractory PTCL (included in the model were brentuximab vedotin, romidepsin, pralatrexate, ifosfamide in combination with carboplatin and etoposide [ICE], and gemcitabine-based regimens). Annual prevalence of patients living progression-free with PTCL in the 1L setting with each prescribed scenario was estimated for 10 years (year 2031) with and without the availability of A+CHP. Results The cumulative number of patients with newly diagnosed PTCL between 2026 and 2031 was estimated at 8,020. The number of patients alive and progression-free based on 1L treatment was estimated at 6,304 in a scenario without A+CHP and 7,414 with A+CHP (Δ+1,110, 17.6% increase) in 2031. It was also estimated that 1,203 patients would progress to second-line treatment with CHOP vs 1,119 patients with 1L A+CHP (Δ-84, 7.0% decrease) in 2031. Conclusions The durable and significant improvements in PFS and OS of A+CHP vs CHOP in the 5-year follow-up data from ECHELON-2 estimated an increase in the number of 1L PTCL patients who remain progression free and alive for greater than 10 years. This improvement in outcomes may translate into an increased prevalence of PTCL patients, reflecting an increased number of patients in remission and options to undergo transplant therapy when necessary. Disclosures Burke: Adaptive Biotechnologies: Consultancy; AstraZeneca: Consultancy; Roche/Genentech: Consultancy; SeaGen: Consultancy, Speakers Bureau; Beigene: Consultancy, Speakers Bureau; Epizyme: Consultancy; AbbVie: Consultancy; Bristol Myers Squibb: Consultancy; X4 Pharmaceuticals: Consultancy; Kymera: Consultancy; MorphoSys: Consultancy; Kura: Consultancy; Verastem: Consultancy. Yu: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Bloudek: Seagen, Inc: Consultancy. Liu: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Fanale: Seagen, Inc: Current Employment, Current equity holder in publicly-traded company. Phillips: Genentech: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; AstraZeneca: Consultancy; Incyte: Consultancy, Other: received travel expenses from Incyte, Research Funding; ADCT, BeiGene, Bristol Myers Squibb, Cardinal Health, Incyte, Karyopharm, Morphosys, Pharmacyclics, Seattle Genetics: Consultancy.

Download Full-text