scholarly journals Real World Treatment Outcomes and Cost Among Newly-Diagnosed Multiple Myeloma Patients Treated with Bortezomib and Dexamethasone in Combination with Cyclophosphamide or Lenalidomide

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5924-5924
Author(s):  
Lin Xie ◽  
Kejal Parikh ◽  
Safiya Abouzaid ◽  
Shivani Pandya ◽  
Onur Baser ◽  
...  
Keyword(s):  
Healthcare Costs ◽  
Research Funding ◽  
Index Date ◽  
Cox Regression ◽  
Treatment Patterns ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Equity Ownership ◽  
Baseline Characteristics

Abstract Background: Despite an increasing incidence of multiple myeloma (MM) with advancing age and life expectancy, there are few real-world claims-based analyses describing treatment patterns and healthcare costs associated with use of novel treatments.1,2 This study aimed to assess treatment patterns and healthcare costs among newly-diagnosed MM patients using the US Medicare database. Methods: This retrospective study identified adult patients with ≥2 claims for MM (International Classification of Diseases, 9th Revision, Clinical Modification code: 203.0x) 30 days apart and ≥1 treatment during the identification period (01JAN2011-30JUN2014) from the 100% Medicare dataset. Medicare dataset contains medical and pharmacy claims submitted by healthcare providers, facilities and pharmacy. It includes comprehensive demographic information for beneficiaries and a longitudinal picture of their healthcare utilizations and costs .The initial course of therapy (COT1) date was the index date and included all treatments prescribed within 60 days of this date. Patients were required to have continuous enrollment for 12 months pre- and ≥6 months post-index date unless the patient died in <6 months (follow-up period), ≥1 full cycle of therapy with a valid COT1 regimen, no evidence of prior MM diagnosis or treatment (including autologous stem cell transplant [ASCT]), and no evidence of ASCT in the follow-up period. COT2 was defined as the earliest occurrence of: addition of a new drug or switch in regimen after the first 60 days, restart of a previous regimen after >180-day gap, or dose increase from maintenance to relapse therapy. Steroids (dexamethasone/prednisone [d]) were assumed to be included regardless of whether or not they were observed during the study period; this did not impact the ongoing COT. Treatment patterns and healthcare costs during the follow-up period were compared among those initiating lenalidomide (R) with bortezomib (V) ± steroids (RVd) and cyclophosphamide (Cy) with bortezomib (bor) ± steroids (CyBorD). Time-to-next treatment (TTNT) was defined as the duration from initiation of COT1 plus any treatment gaps until the initiation of COT2. Kaplan Meier (KM), Cox regression analyses and a generalized linear model (GLM) were performed to evaluate TTNT, assess the impact of various predictors on TTNT, and estimate the 12-month per patient per month (PPPM) total healthcare costs respectively among patients initiating RVd and CyBorD. Results:After accounting for the patient selection criteria, 9.9% (n=345) of patients initiated RVd and 5.0% (n=175) initiated CyBorD as COT1. CyBorD-treated patients were significantly older (76.1 vs. 74.2 years, p=0.0009) with a higher age-adjusted Charlson Comorbidity Index score (9.5 vs 8.8, p=0.0119). The overall mean duration of COT1 was significantly longer among patients treated with RVd vs CyBorD (13.2 vs 8.5 months, p<0.0001). Among patients who completed COT1, the mean duration of COT1 was longer for patients treated with RVd vs. CyBorD (12.8 vs 6.7 months, p<0.0001). A higher percentage of patients treated with CyBorD progressed to COT2 (27.4%, vs 21.7% p=0.1491) versus RVd, however no significant difference was observed. Among patients who progressed to COT2, TTNT was significantly shorter among those treated with CyBorD vs RVd (Mean: 7.9 vs 15.9 months, p<0.0001). KM analysis suggested that patients initiating CyBorD progressed much faster than patients receiving RVd. After adjusting for baseline characteristics using Cox regression, TTNT remained significantly shorter for CyBorD vs. RVd treated patients (hazard ratio: 2.2, 95% confidence interval: 1.5-3.4, p=0.0002). Results from GLM analysis suggested that adjusted total PPPM cost during 12 months follow up was higher among patients treated with RVd vs. CyBorD ($13,941 vs $9,340, p=0.0001), and the majority of the extra cost are due to higher pharmacy costs for patients treated with RVd. Conclusion: Patients on RVd incurred higher costs, however, they progressed significantly slower and their TTNT was almost twice as long as for CyBorD patients. The difference remained significant after controlling for baseline characteristics including markers for higher disease severity among patients on CyBorD. 1Song X, et al. Curr Med Res Opin 2015;32(1):95-103 2Teitelbaum A, et al. Oncologist 2013;18:37-45 Disclosures Xie: Celgene: Research Funding. Parikh:Celgene Corporation: Employment, Equity Ownership, Research Funding. Abouzaid:Celgene Corporation: Employment, Equity Ownership, Research Funding. Pandya:Celgene: Research Funding. Baser:Janssen Pharmaceuticals: Research Funding. Patel:Celgene: Consultancy.

scholarly journals Treatment Patterns Among Newly Diagnosed Multiple Myeloma Patients in the United States Veteran Population (2010-2015)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5952-5952
Author(s):  
Kejal Parikh ◽  
Shivani Pandya ◽  
Safiya Abouzaid ◽  
Onur Baser ◽  
Lin Xie ◽  
...  
Keyword(s):  
Research Funding ◽  
Cox Regression ◽  
Treatment Patterns ◽  
Novel Therapies ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Chemotherapy Agent ◽  
The Us ◽  
Equity Ownership

Abstract Background: Despite a relatively higher incidence in the veteran population, there are few real-world claims-based analyses to describe Multiple Myeloma (MM) treatment patterns among this patient population (Landgren O, Blood, 2006). This study aimed to assess treatment patterns among newly diagnosed MM (ndMM) patients using the US Veteran Health Administration (VHA) data. Methods: This retrospective study identified adult patients with ≥2 claims for MM (ICD-9-CM code: 203.0x) 30 days apart and ≥1 treatment during identification period (1OCT2011-31MAR2015) from the VHA dataset. The initial course of therapy (COT1) date was the index date and included all treatments prescribed within 60 days of this date. Patients were required to have continuous enrollment for 12 months pre- and ≥6 months post-index date unless patients died within 6 months (follow up period), ≥1 full cycle of therapy with a valid COT1 regimen, no evidence of prior MM diagnosis or treatment (including autologous stem cell transplant (ASCT)), and no evidence of ASCT in the follow up period. A subsequent COT (COT2) was defined as the earliest occurrence of: the addition of a new drug or switch in regimen after the first 60 days, restart of a previous regimen after >180-day gap, or a dose increase from maintenance to relapse therapy. Dexamethasone/prednisone[d] which were assumed to be included regardless of whether or not they were observed during the study period did not impact the ongoing COT. Treatment patterns during the follow-up period were initially examined among patients treated with novel (lenalidomide [R] and/or bortezomib [V] with or without chemotherapy agents) and non-novel therapies (≥1 chemotherapy agent, steroid monotherapy) and then compared among those initiating Rd and Vd. Time to next treatment (TTNT) was defined as the duration from initiation of COT1 plus any gaps before COT2. Kaplan Meier and Cox regression analyses were performed to evaluate TTNT and assess the impact of various predictors on TTNT among patients initiating Rd and Vd. Results: Of 1,183 patients that met the inclusion criteria, 55.4% (n=655) were treated with novel therapies and 44.6% (n=528) with non-novel therapies. Among patients treated with novel therapy, the majority initiated Rd (47.8%; n=313) as COT1 followed by Vd (31.2%; n=204), Vd with cyclophosphamide (11.5%; n=75), RVd (6.6%; n=43), Vd with a chemotherapy agent (2.4%; n=16) and Rd with a chemotherapy agent (0.6%; n=4).Rd initiators were significantly older (75.1 vs 70.6 years, p=0.0002) and a higher percentage was white (69.7% vs 47.0%; p<0.0001) than Vd treated patients. While the Charlson Comorbidities Index score did not differ between the two groups (3.6 vs 4.0, p=0.0583), a significantly higher percentage of patients treated with Vd had some comorbidities including hepatitis and renal disease. Among patients with laboratory tests, patients treated initially with Vd had lower hemoglobin (10.8 vs 11.4 g/dl, p=0.0012) and higher serum creatinine (2.3 vs 1.4 mg/dl, p<0.0001) during the pre-index period. The overall average treatment duration in COT1 was significantly longer among patients treated with Rd vs Vd (10.9 vs 7.0 months, p<0.0001). Among patients who were still on active COT1, the mean duration in COT1 was longer among patients treated with Rd than Vd (18.7 vs 13.3 months, p=0.0061). A significantly higher percentage of patients treated with Vd progressed to COT2 (52.5%, vs 26.2% p<0.0001) as compared to Rd. Among patients who progressed to COT2, those treated with Vd had a shorter TTNT compared to Rd (Mean: 9.3 vs 12.8 months, p=0.0049). After adjusting for baseline demographic and clinical factors using Cox regression, TTNT remained significantly shorter for Vd vs those treated with Rd (HR: 2.67, 95% CI: 1.9-3.7, p <0.0001). Conclusion: Slightly over half of MM patients in the US Veteran population were treated with a regimen containing novel therapies; Rd and Vd were the most commonly observed among these. Patients treated initially with Vd had a significantly shorter TTNT compared to those treated with Rd. The difference remained significant after controlling for baseline characteristics including markers for higher disease severity among patients on Vd. Disclosures Parikh: Celgene Corporation: Employment, Equity Ownership, Research Funding. Pandya:Celgene: Research Funding. Abouzaid:Celgene Corporation: Employment, Equity Ownership, Research Funding. Baser:Celgene: Research Funding. Xie:Celgene: Research Funding. Patel:Celgene: Consultancy.

scholarly journals Treatment Patterns and Outcomes in Elderly Patients with Newly Diagnosed Multiple Myeloma: Results from the Connect® MM Registry

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3129-3129
Author(s):  
Hans C. Lee ◽  
Sikander Ailawadhi ◽  
Cristina Gasparetto ◽  
Sundar Jagannath ◽  
Robert M. Rifkin ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Causes Of Death ◽  
Age Groups ◽  
Treatment Patterns ◽  
Age Group ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Background: Multiple myeloma (MM) is common among the elderly, with 35% of patients (pts) diagnosed being aged ≥75 years (y). With increasing overall life expectancy, the incidence and prevalence of newly diagnosed and previously treated MM patients ≥80 y is expected to increase over time. Because elderly pts are often excluded from clinical trials, data focused on their treatment patterns and clinical outcomes are lacking. The Connect® MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed MM (NDMM) designed to examine real-world diagnostic patterns, treatment patterns, clinical outcomes, and health-related quality of life patient-reported outcomes. This analysis reviews treatment patterns and outcomes in elderly pts from the Connect MM Registry. Methods: Pts enrolled in the Connect MM registry at 250 community, academic, and government sites were included in this analysis. Eligible pts were adults aged ≥18 y with symptomatic MM diagnosed ≤2 months before enrollment, as defined by International Myeloma Working Group criteria; no exclusion criteria were applied. For this analysis, pts were categorized into 4 age groups: <65, 65 to 74, 75 to 84, and ≥85 y. Pts were followed from time of enrollment to the earliest of disease progression (or death), loss to follow-up, or data cutoff date of February 7, 2019. Descriptive statistics were used for baseline characteristics and treatment regimens. Survival outcomes were analyzed using Cox regression. Time to progression (TTP) analysis excluded causes of death not related to MM. Results: Of 3011 pts enrolled (median age 67 y), 132 (4%) were aged ≥85 y, and 615 (20%) were aged 75-84 y at baseline. More pts aged ≥85 y had poor prognostic factors such as ISS stage III disease and reduced hemoglobin (<10 g/dL or >2 g/dL <LLN) compared with other age groups, although no notable differences between creatinine and calcium levels were observed across age groups (Table). A lower proportion of elderly pts (75-84 and ≥85 y) received triplet regimens as frontline therapy. More elderly pts received a single novel agent, whereas use of 2 novel agents was more common in younger pts (Table). The most common frontline regimens among elderly pts were bortezomib (V) + dexamethasone (D), followed by lenalidomide (R) + D, whereas those among younger pts included RVD, followed by VD and CyBorD (Table). No pt aged ≥85 y, and 4% of pts aged 75-84 y received high-dose chemotherapy and autologous stem cell transplant (vs 61% in the <65 y and 37% in the 65-74 y age group). The most common maintenance therapy was RD in pts ≥85 y (although the use was low) and R alone in other age groups (Table). In the ≥85 y group, 27%, 10%, and 4% of pts entered 2L, 3L, and 4L treatments respectively, vs 43%, 23%, and 13% in the <65 y group. Progression-free survival was significantly shorter in the ≥85 y age group vs the 75-84 y age group (P=0.003), 65-74 y age group (P<0.001), and <65 y age group (P<0.001; Fig.1). TTP was significantly shorter in the ≥85 y group vs the <65 y group (P=0.020); however, TTP was similar among the 65-74 y, 75-84 y, and ≥85 y cohorts (Fig. 2). Overall survival was significantly shorter in the ≥85 y group vs the 75-84 y, 65-74 y, and <65 y groups (all P<0.001; Fig. 3). The mortality rate was lowest (46%) during first-line treatment (1L) in pts aged ≥85 y (mainly attributed to MM progression) and increased in 2L and 3L (47% and 54%, respectively); a similar trend was observed in the younger age groups. The main cause of death was MM progression (29% in the ≥85 y vs 16% in the <65 y group). Other notable causes of death in the ≥85 y group included cardiac failure (5% vs 2% in <65 y group) and pneumonia (5% vs 1% in <65 y group). Conclusions: In this analysis, elderly pts received similar types of frontline and maintenance regimens as younger pts, although proportions varied with decreased use of triplet regimens with age. Considering similarities in TTP across the 65-74 y, 75-84 y, and ≥85 y cohorts, these real-world data support active treatment and aggressive supportive care of elderly symptomatic pts, including with novel agents. Additionally, further clinical studies specific to elderly patients with MM should be explored. Disclosures Lee: Amgen: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ailawadhi:Janssen: Consultancy, Research Funding; Takeda: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Cellectar: Research Funding. Gasparetto:Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Jagannath:AbbVie: Consultancy; Merck & Co.: Consultancy; Bristol-Myers Squibb: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy. Rifkin:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Narang:Celgene: Speakers Bureau. Terebelo:Celgene: Honoraria; Jannsen: Speakers Bureau; Newland Medical Asociates: Employment. Toomey:Celgene: Consultancy. Hardin:Celgene: Membership on an entity's Board of Directors or advisory committees. Wagner:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Cancer Society: Other: Section editor, Cancer journal. Omel:Celgene, Takeda, Janssen: Other: Patient Advisory Committees. Srinivasan:Celgene: Employment, Equity Ownership. Liu:TechData: Consultancy. Dhalla:Celgene: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Abonour:BMS: Consultancy; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.

Clinical Outcomes of Patients with Newly Diagnosed Multiple Myeloma Receiving Triplet Therapy in the Connect MM® Disease Registry

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4229-4229
Author(s):  
Jatin J. Shah ◽  
Rafat Abonour ◽  
Mohit Narang ◽  
Jayesh Mehta ◽  
Howard R. Terebelo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Advisory Committees ◽  
Risk Of Death ◽  
Equity Ownership ◽  
Triplet Regimen

Abstract Introduction: Triplet therapies are used for treatment (Tx) of both transplant-eligible and -ineligible patients (pts) with newly diagnosed multiple myeloma (NDMM). Actual patterns and outcomes of Tx are not fully understood. Connect MM® is the first and largest multicenter, US-based, prospective observational cohort study designed to characterize Tx patterns and outcomes for pts with NDMM. This analysis describes demographic and disease characteristics of pts who received triplet Tx as an induction regimen and for whom transplant was or was not intended. The analysis explores the relationship of these factors with overall survival (OS) and other efficacy endpoints. Patients and Methods: Pts aged ≥ 18 y with NDMM within 60 days of diagnosis were eligible for enrollment regardless of disease severity, medical history, or comorbidities. Data including transplant intent (yes/no) was collected at baseline; follow-up data was collected quarterly thereafter. Based on the initial intent, 2 groups were identified: patients with intent to transplant who received transplant (TT) and pts with no intent to transplant who did not receive a transplant (NT). Triplet Tx was defined as the combination of ≥ 3 concurrent therapeutic agents in the first course of Tx (within 56 days of study entry). KM analysis adjusted for age was conducted for OS. Because decisions on use of transplant and triplet therapy are influenced by multiple factors, a multivariable Cox regression analysis was performed to evaluate the contribution of the triplet therapy (yes/no) to OS and was adjusted for other variables, including age, comorbidities, and ISS staging. Results: Between September 2009 and December 2011, 1493 pts were enrolled. This analysis was on 1436 pts: 650 pts with transplant intent and 786 pts without transplant intent. The data cutoff date was November 30, 2014, and the median follow-up for overall survival (OS) was 33.8 mos. Of pts with transplant intent, 451 (69%) received transplant (TT) and 199 (31%) did not. Of pts without transplant intent, 62 (8%) received transplant and 724 (92%) did not (NT). The abstract focuses on TT and NT groups only. NT pts tended to be older and have more advanced ISS staging and higher β2-microglobulin levels than TT pts (Table). The most common triplet regimen given during the first course treatment (within 56 days) was lenalidomide, bortezomib, and dexamethasone (RVd). RVd was administered to 34% of the NT pts (76/225) and 59% of the TT pts (152/257). The most common non-triplet regimen was bortezomib and dexamethasone (Vd), which was given to 31% of NT pts (156/499) and 38% of TT pts (73/194). Within the NT group, pts given triplet Tx had a lower risk of death than those who did not receive triplet Tx (P = .0013). The multivariable analysis found triplet Tx to be associated with a 36% reduced risk of death (hazard ratio [HR] = 0.64 [95% CI, 0.50-0.82]; P = .001). ISS disease stage (HR = 1.43 [95% CI, 1.21-1.69]; P < .001) and history of diabetes (HR = 1.38 [95% CI, 1.08-1.78]; P = .012) were negative prognostic factors for OS. Within the TT group, pts who received triplet Tx did not attain an OS benefit (P = .8993), and no baseline characteristics were significantly associated with OS. These results may be limited by other factors not considered that may have influenced physicians' choice of treatment, including the use of maintenance therapy and a short follow-up period of 33.8 months. Conclusions: Triplet Tx as a first regimen is associated with longer OS in pts without transplant intent who did not receive a transplant. RVd and Vd were the most common first Tx regimens, respectively. Continued follow-up of these pts and enrollment of an additional cohort will provide additional data with mature follow-up. Table 1. Table 1. Disclosures Shah: Bristol-Myers Squibb: Research Funding; Array: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees. Abonour:Celgene: Research Funding, Speakers Bureau. Narang:Celgene: Speakers Bureau. Mehta:Celgene Corporation: Speakers Bureau. Terebelo:Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacylics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Gasparetto:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millennium: Honoraria, Other: Export Board Committee, Speakers Bureau. Toomey:Celgene: Consultancy. Hardin:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Srinivasan:Celgene Corporation: Employment, Equity Ownership. Larkins:Celgene Corporation: Employment, Equity Ownership. Nagarwala:Celgene Corporation: Employment, Equity Ownership. Rifkin:Onyx Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Millennium Pharmaceuticals, Inc., Cambridge, MA, USA, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Real-World Analysis of Ruxolitinib Treatment Patterns and Outcomes Among Patients with Myelofibrosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4750-4750 ◽  
Author(s):  
Tanya Burton ◽  
Kejal Parikh ◽  
Manish Patel ◽  
Kevin Sundquist ◽  
Lincy S. Lal ◽  
...  
Keyword(s):  
Health Plan ◽  
Research Funding ◽  
Index Date ◽  
Myeloproliferative Neoplasm ◽  
Treatment Patterns ◽  
Systemic Steroid ◽  
Administrative Claims ◽  
Employment Equity ◽  
Oncology Research ◽  
Equity Ownership

Background: Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by bone marrow fibrosis, splenomegaly, cytopenias, and poor survival. Ruxolitinib (RUX) is the only approved treatment for Intermediate or High-risk MF. In a previous study, we have shown almost 1 in 3 patients initiating RUX had dose modifications during the first 3 months of treatment (Burton T et al. HemaSphere 2019). The objective of this study was to assess RUX treatment patterns among patients with MF. Methods: This retrospective analysis used administrative claims data from a large US health plan to identify adults (aged ≥ 18 years) with ≥ 1 claim for RUX and ≥ 2 non-diagnostic medical claims for primary (International Classification of Diseases [ICD] 9th or 10th Revision [9/10]: 238.76, D47.4) or secondary MF (ICD-9/10: 289.83, D75.81) from January 1, 2012 to June 30, 2018. The first RUX claim on or after the first MF claim defined the index date. Included patients were continuously enrolled in a commercial or Medicare Advantage health plan for 3 months before the index date (pre-index period) and 6 months on or after the index date (post-index period). Clinical characteristics, MF-related treatments, health care resource utilization (HCRU), and costs were assessed during the pre- and post-index periods. Costs were adjusted to 2018 US dollars using the medical component of the Consumer Price Index. Cohorts were created based on the maximum (max) RUX daily dose observed during the 6-month post-index period: suboptimal max < 30 mg/day (SUB); and optimal max ≥ 30 mg/day (OPT). All variables were analyzed descriptively. Results: Among 495 eligible patients, mean (SD) age was 69.4 (10.3) years; 54.1% were male; and 25% had a primary MF diagnosis code. Median initial RUX dose was 30 mg/day and patients continued with this dose for a mean (SD) of 70.0 (45.8) days. RUX dose was modified for 19.4% of patients during the 6-month post-index period, and the distribution of max RUX daily doses was: < 15 mg (13.7%), 15-29 mg (24.9%), 30-40 mg (55.8%), and > 40 mg (5.7%). Two groups based on max RUX dosing were further analyzed: 191 (38.6%) in the SUB cohort (< 30 mg), and 304 (61.4%) in the OPT cohort (≥ 30 mg). Patients in the SUB cohort were older than patients in the OPT cohort (SUB: mean 70.8 [SD 10.1] years; OPT: mean 68.5 [SD 10.3] years; P = 0.013), but the mean Charlson Comorbidity Index scores did not differ (SUB: mean 1.6 [SD 1.8]; OPT: mean 1.5 [SD 1.8]; P = 0.601). Rates of anemia were higher at baseline for the SUB cohort than the OPT cohort (SUB: 64.9%; OPT: 53%; P = 0.009). During the 6-month post-index period, compared with patients in the OPT cohort, patients in the SUB cohort had a higher proportion of thrombocytopenia (SUB: 31.4%; OPT: 22.7%; P = 0.03). Nearly half (45.5%) the sample used a supportive agent such as an androgen, systemic steroid, or erythropoiesis-stimulating agent during the post-index period (SUB: 48.2%; OPT: 43.8%; P = 0.34). With respect to HCRU and costs, the SUB cohort had a higher proportion of emergency department (ED) visits than the OPT cohort during baseline (SUB: 31.4%; OPT: 23.4%; P = 0.048); and baseline total mean (SD) all-cause costs were USD 18,079 (21,876) overall, USD 18,908 (24,411) for the SUB cohort, and USD 17,559 (20,145) for the OPT cohort (P = 0.523). During the 6-month follow-up period, 31.1% of patients had ≥ 1 ED visit (SUB: 35.1%; OPT: 28.6%; P = 0.131), 22.8% had ≥ 1 inpatient (IP) hospitalization (SUB: 24.6%; OPT: 21.7%; P = 0.455), and total mean (SD) all-cause costs were USD 94,498 (97,391) overall (SUB: USD 93,289 [115,418]; OPT: USD 95,258 [84,315]; P = 0.839). Conclusion: In this study, patients with MF treated with RUX experienced significant disease burden and high costs, regardless of dose. Both anemia and thrombocytopenia were observed along with nearly half of patients using a supportive agent. Given the large proportion of patients with a dose adjustment, suboptimal dosing, and an IP hospitalization, there continues to be a need for additional therapeutic options for patients with MF. Disclosures Parikh: Celgene Corporation: Employment, Equity Ownership. Patel:Celgene Corporation: Employment, Equity Ownership. Sundquist:Optum: Employment, Equity Ownership. Lal:Optum: Employment. Copher:Celgene Corporation: Employment. Gerds:Roche: Research Funding; Incyte: Consultancy, Research Funding; Sierra Oncology: Research Funding; CTI Biopharma: Consultancy, Research Funding; Imago Biosciences: Research Funding; Celgene Corporation: Consultancy, Research Funding; Pfizer: Consultancy.

scholarly journals Real-World Treatment Patterns and Overall Survival Among Medicare Fee-for-Service Beneficiaries Newly Diagnosed with Peripheral T-Cell Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3492-3492
Author(s):  
Anne Shah ◽  
Allison Petrilla ◽  
Mayvis Rebeira ◽  
Joseph Feliciano ◽  
Thomas W. LeBlanc ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Brentuximab Vedotin ◽  
Treatment Patterns ◽  
Fee For Service ◽  
Newly Diagnosed ◽  
Medicare Beneficiaries ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Background: Peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous group of lymphoid malignancies characterized by a clinically aggressive course with poor prognosis. A majority of PTCL patients are ≥60 years of age and typically present with advanced stage disease and multiple comorbidities. There remains no consensus standard of care for patients with most PTCL subtypes. Multi-agent chemotherapy, consisting of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or CHOP with etoposide (CHOEP), are guideline recommended options for nodal subtypes. Limited contemporary real-world data exist on the treatment patterns and overall survival (OS) of PTCL patients treated with CHOP or non-CHOP regimens in the United States before the FDA approval of brentuximab vedotin in combination with chemotherapy in November 2018 based on the ECHELON-2 trial. Objective: To evaluate treatment patterns and OS prior to the approval of brentuximab vedotin among Medicare Fee-for-Service (FFS) beneficiaries newly diagnosed with PTCL. Methods: The 100% sample of Medicare FFS claims (Parts A/B/D) was used to identify patients aged ≥65 years with ≥1 inpatient or ≥2 distinct outpatient diagnosis claims for PTCL (index event) from January 2011 to December 2017. Patients were required to have a least 6 months prior and 12 months post-index continuous Medicare enrollment, and were followed until disenrollment, death, or the end of the study period, whichever occurred first. OS, defined as the time from initial episode or treatment start date to the validated date of death, was measured using the Kaplan-Meier method; patients without a death date were assumed to be alive at the time of analysis and were censored. Results: A total of 2551 Medicare FFS beneficiaries with a PTCL diagnosis met study criteria and were included for analysis. The majority of patients were white (86.9%), over half were male (52.9%), and mean age was 75 years. Patients had multiple comorbidities at diagnosis (Charlson Comorbidity Index (CCI) score 4.47), including hypertension (77.3%), diabetes (32.9%), and chronic obstructive pulmonary disease (28.1%). Among the 2551 patients in the study cohort, 62.4% (n=1593 of 2551) received at least one identifiable drug regimen; 25.5% of treated patients received CHOP (n=407), 3.1% CHOEP (n=50) and 71.2% (n=1134) other regimens. Of patients treated with other regimens, 37.7% (n=427) received steroids only, 22.4% (n=254) steroids with unidentifiable chemotherapy, 6.9% (n=78) cyclophosphamide, 6.2% (n=70) methotrexate, 4.6% (n=52) brentuximab vedotin, 3.6% (n=41) bendamustine, 3.5% (n=40) romidepsin, and 15.2% (n=172) other therapy combinations. Among patients who were treated with CHOP, 16.6% (n=66) received an identifiable second line of therapy (LoT), 48.7% (n=194) an unidentifiable second LoT, and the remainder (34.7%, n=138) had no evidence of further anti-cancer treatment. The median time from CHOP initiation to a subsequent LoT was 5.6 months. The mean baseline CCI score for patients treated with CHOP was 4.33 (±2.93) compared with 4.76 (±2.97) for patients treated with other therapies (p=0.0118). In patients receiving an identifiable first LoT, median OS among CHOP and non-CHOP recipients was 4.8 years (95% CI 3.0-6.1) and 4.4 years (95% CI 3.0-4.9), respectively (Table). The 5-year OS estimate was 49% in patients receiving CHOP compared with 46% for non-CHOP recipients. Conclusions: Fewer than 30% of Medicare beneficiaries newly diagnosed with PTCL were treated with intensive chemotherapy as first LoT. Acknowledging a possible selection bias for more fit PTCL patients receiving CHOP, this group had increased OS compared with patients receiving non-CHOP therapy. However, the 5-year OS across all cohorts was less than 50%. New therapies such as brentuximab vedotin may fill the need for PTCL Medicare beneficiaries who may not be able to tolerate CHOP or CHOP-based regimens. Disclosures Shah: Avalere Health, An Inovalon Company: Employment. Petrilla:Avalere Health, An Inovalon Company: Employment. Rebeira:Seattle Genetics: Employment. Feliciano:Seattle Genetics: Employment, Equity Ownership. LeBlanc:Astra Zeneca: Consultancy, Research Funding; Duke University: Research Funding; Jazz Pharmaceuticals: Research Funding; Daiichi-Sankyo: Membership on an entity's Board of Directors or advisory committees; Helsinn: Consultancy; Agios: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NINR/NIH: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Otsuka: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Research Funding; CareVive: Consultancy; Celgene: Honoraria; Flatiron: Consultancy; American Cancer Society: Research Funding; Heron: Membership on an entity's Board of Directors or advisory committees; Medtronic: Membership on an entity's Board of Directors or advisory committees; Pfizer Inc: Consultancy. Lisano:Seattle Genetics, Inc.: Employment, Equity Ownership.

Nilotinib Versus Imatinib in Patients (pts) with Newly Diagnosed Philadelphia Chromosome-Positive (Ph+) Chronic Myeloid Leukemia in Chronic Phase (CML-CP): ENESTnd 36-Month (mo) Follow-up

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 452-452 ◽  
Author(s):  
Giuseppe Saglio ◽  
Philipp D. LeCoutre ◽  
Ricardo Pasquini ◽  
Saengsuree Jootar ◽  
Hirohisa Nakamae ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Philadelphia Chromosome ◽  
Safety Data ◽  
Molecular Response ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership

Abstract Abstract 452FN2 Background: In ENESTnd, pts treated with nilotinib demonstrated higher and faster rates of major molecular response (MMR, ≤ 0.1% BCR-ABLIS), deeper molecular response (MR4, ≤ 0.01%IS and MR4.5, ≤ 0.0032%IS), and complete cytogenetic responses (CCyR) along with significantly lower rates of progression to AP/BC and fewer CML-related deaths compared with imatinib by 12 and 24 mo. Here, we report data with a minimum follow-up of 24 mo; however, efficacy and safety data based on considerably longer follow-up of ≥ 36 mo will be presented. As demonstrated in IRIS and other imatinib trials, most pts who progress on imatinib do so within the first 3 years of therapy. Thus, this 36-mo update of ENESTnd will be important to further verify the benefits of nilotinib in newly-diagnosed pts. Methods: 846 adult pts with newly-diagnosed Ph+ CML-CP were randomized to nilotinib 300 mg twice daily (BID) (n = 282), nilotinib 400 mg BID (n = 281), or imatinib 400 mg once daily (QD) (n = 283). MMR, MR4, MR4.5, time to progression to AP/BC on treatment, progression-free survival (PFS) on treatment, and overall survival (OS) were evaluated. Results: By 24 mo, both doses of nilotinib demonstrated significantly higher rates of MMR, MR4, and MR4.5 vs imatinib (Table). Nilotinib-treated pts achieved median BCR-ABLIS levels of 0.09% (300 mg BID) and 0.10% (400 mg BID) by 12 mo, while this level of reduction was not observed before 24 mo on imatinib. More pts with CCyR achieved MMR at 12 and 24 mo with either dose of nilotinib vs imatinib (Table). Regardless of Sokal risk, rates of MMR and MR4.5 were higher for nilotinib at both doses vs imatinib (Table). Progression to AP/BC (excluding clonal evolution [CE]) on treatment was significantly lower for nilotinib vs imatinib (2 pts and 3 pts with nilotinib 300 mg BID [P = .0059] and 400 mg BID [P =.0196]), respectively vs 12 pts with imatinib). After achieving CCyR, 4 pts treated with imatinib progressed to AP/BC and 2 pts treated with nilotinib 400 mg BID progressed after achieving both CCyR and MMR (1 also achieved MR4). No pt who achieved MR4.5 progressed at any time. All but 1 pt who progressed to AP/BC on treatment were in the intermediate and high Sokal risk groups; 1 pt treated with nilotinib 400 mg BID progressed in the low Sokal risk group who had an E255V mutation at progression. When considering progression events of pts after discontinuation of treatment, an additional 7, 2, and 6 events (excluding CE) were observed with nilotinib 300 mg BID, nilotinib 400 mg BID and imatinib, respectively. Twice as many pts had emergent mutations on imatinib (n = 20) vs nilotinib (n = 10 on 300 mg BID; n = 8 on 400 mg BID). At 24 mo, OS remained similar in all groups, but there were fewer CML-related deaths in both nilotinib 300 mg BID (5 pts) and nilotinib 400 mg BID (3 pts) arms vs imatinib (10 pts). Both drugs were well tolerated and few new adverse events (AEs) and lab abnormalities were observed between 12- and 24-mo of follow-up. Nilotinib 300 mg BID had the fewest discontinuations due to AEs/lab abnormalities (9% vs 13% and 10% with nilotinib 400 mg BID and imatinib, respectively). Conclusions: With a minimum follow-up of 24 mo, nilotinib continued to demonstrate superiority vs imatinib with faster and deeper molecular responses and a significantly decreased risk of progression. These data support the use of nilotinib as a standard of care option in newly-diagnosed adult pts with Ph+ CML-CP. Disclosures: Saglio: Novartis Pharmaceutical: Consultancy, Speakers Bureau; Bristol-Myers Squibb: Consultancy, Speakers Bureau; Pfizer: Consultancy. Off Label Use: Nilotinib is a safe and effective treatment for patients with CML. LeCoutre:Novartis: Honoraria, Research Funding, Speakers Bureau; Bristol Myers Squibb: Honoraria. Pasquini:Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Nakamae:Novartis: Consultancy, Research Funding, Speakers Bureau; BMS: Consultancy, Research Funding, Speakers Bureau. Flinn:nOVARTIS: Research Funding. Hochhaus:Novartis Pharmaceutical: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding. Hughes:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Ariad: Honoraria, Membership on an entity's Board of Directors or advisory committees. Larson:Novartis Pharmaceuticals: Consultancy, Honoraria, Research Funding. Hoenekopp:Novartis Pharmaceutical: Employment, Equity Ownership. Gallagher:Novartis: Employment. Yu:Novartis: Employment, Equity Ownership. Blakesley:Novartis Pharmaceutical: Employment. Kim:BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding. Kantarjian:Novartis: Consultancy; Novartis: Research Funding; Pfizer: Research Funding; BMS: Research Funding.

scholarly journals Quality-Adjusted Survival for Low-Dose Cytarabine (LDAC) Versus Glasdegib+LDAC Among Newly Diagnosed Acute Myeloid Leukemia Patients Who Are Not Candidates for Intensive Chemotherapy: A Q-TWiST Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2610-2610 ◽  
Author(s):  
Youngmin Kwon ◽  
Timothy J Bell ◽  
Caitlyn Solem ◽  
Joseph C Cappelleri ◽  
Courtney Johnson ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myeloid Leukemia ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Equity Ownership ◽  
Relative Gains ◽  
Mean Time ◽  
Low Dose Cytarabine

Introduction: The efficacy and safety of glasdegib (a selective oral inhibitor of hedgehog signaling pathway) in combination with low-dose cytarabine (LDAC) was evaluated in a randomized, phase 2 trial of newly diagnosed acute myeloid leukemia (AML) patients (BRIGHT AML 1003; NCT01546038). Patients receiving glasdegib+LDAC experienced statistically significant and meaningful gains in overall survival (OS) compared with patients receiving LDAC alone (median OS [95% CI]): 8.3 months [4.7-12.2] vs 4.3 months [1.9-5.7]). This analysis examined whether quality-adjusted survival improvements were similarly observed using a quality-adjusted time without symptoms of disease progression or toxicities (Q-TWiST) approach to evaluate possible trade-offs between time with adverse events (toxicities), time in relapse/progression (i.e., with symptoms of disease), and 'good' survival (i.e., time without toxicities or symptoms of progression [TWiST]) when comparing regimens. Methods: OS in BRIGHT AML 1003 data, restricted to a follow-up of 20 months, was partitioned into time with toxicity (TOX: grade 3+ adverse events prior to progression), TWiST, and time post-progression (REL). Progression was defined as treatment discontinuation due to insufficient clinical response or death; patients who discontinued for other reasons (including adverse events) were censored at the date of discontinuation unless death occurred within 28 days of discontinuation. Q-TWiST was calculated by multiplying restricted mean time in each state by respective utilities (U) and then summing up the utility-adjusted time. Base case analysis used U(TOX)=U(REL)=0.5 and U(TWiST)=1.0; threshold analyses were performed varying U(TOX) and U(REL) jointly each from 0 to 1. Relative gains in Q-TWiST (i.e., Q-TWiST difference (combination vs LDAC) / OS in LDAC arm) of ≥15% were considered clearly clinically meaningful per the clinical literature. Sensitivity analysis varied the length of follow-up and AE definitions; subgroup analyses were also performed. 95% confidence intervals were obtained using the bootstrap procedure. Results: At 20 months of follow-up, the survival rate for glasdegib+LDAC and LDAC arm was 28.2% and 7.9%, respectively. Glasdegib+LDAC patients (n=78) compared with LDAC patients (n=38) had significantly longer mean time in TWiST (+3.4 [95% confidence interval: 1.8, 5.2] months) and TOX (+0.8 [0.1, 1.6] months), and longer but non-significant REL (+0.3 [-1.9, 2.3] months). Q-TWiST was 4.0 [2.1, 5.8] months longer for glasdegib+LDAC, translating into a 75% relative improvement in quality-adjusted survival relative to LDAC alone. In threshold analyses, absolute and relative Q-TWiST gains ranged from 3.5 to 4.5 months and 66% to 85%, respectively (Table 1). They exceeded the clinically meaningful threshold for gains in Q-TWiST and were statistically significant across all combinations of U(TOX) and U(REL). Results were robust to length of follow-up 6 to 24 month and remained significant when including all adverse events regardless of grade. Discussions/Conclusions: Glasdegib+LDAC is an add-on therapy that has demonstrated significant survival benefits for newly diagnosed AML patients who are unable to receive intensive chemotherapy. While patients can experience a longer time with toxicities from receiving glasdegib+LDAC (as expected since it is given as an add-on therapy), the trade-off can still be favorable as the treatment provides added time spent in 'good' health (i.e., a significantly longer time in TWiST). In the BRIGHT AML 1003 cohort, the relative gains in OS greatly exceeded previously established thresholds for being clearly clinically meaningful, which suggests that the benefits of glasdegib+LDAC vs LDAC alone outweigh the risks. Table 1 Disclosures Kwon: Pfizer Inc.: Research Funding; Pharmerit International: Employment. Bell:Pfizer Inc.: Employment, Equity Ownership. Solem:Pharmerit International: Employment; Pfizer Inc.: Research Funding. Cappelleri:Pfizer: Employment, Equity Ownership. Johnson:Pfizer Inc.: Research Funding; Pharmerit International: Employment. Bhattacharyya:Pfizer Inc: Employment, Equity Ownership. Hoang:Pfizer Inc.: Employment, Equity Ownership. Cortes:Novartis: Consultancy, Honoraria, Research Funding; Biopath Holdings: Consultancy, Honoraria; Takeda: Consultancy, Research Funding; BiolineRx: Consultancy; Forma Therapeutics: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding; Astellas Pharma: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding; Merus: Consultancy, Honoraria, Research Funding; Immunogen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Sun Pharma: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding.

A New Multinational Observational Study In Multiple Myeloma: Initial Report Of The PREAMBLE Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1964-1964
Author(s):  
Ravi Vij ◽  
Mehdi M. Moezi ◽  
Robin Foà ◽  
Gordon Cook ◽  
Antonio Palumbo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Research Funding ◽  
Clinical Effectiveness ◽  
Novel Therapies ◽  
Employment Equity ◽  
The Us ◽  
Equity Ownership ◽  
Baseline Characteristics

Abstract Introduction The advent of novel immunomodulatory drugs (IMiDs) and proteasome inhibitors (PIs) have improved clinical outcomes of multiple myeloma (MM) in the past decade. Clinical trial data have shown combination novel therapies (IMiD+PI) can provide even further improvement. The PREAMBLE (Prospective Research Assessment in Multiple Myeloma: an Observational Evaluation) is a global study designed to evaluate clinical effectiveness, healthcare resource utilization, and patient-reported outcomes associated with novel therapies for treatment of relapsed or refractory MM (R/R MM) in the real-world daily practices in the US and Europe. We describe the study design and baseline characteristics of the first 111 patients enrolled. Methods This is a prospective, observational, longitudinal cohort study of adult patients with R/R MM who received at least 1 prior therapy and initiated treatment with IMiDs, PIs, or IMiDs+PIs within 90 days prior to or 30 days after enrollment. Follow-up is up to 3 yrs after consent. Patients receive standard of care treatment as determined by the treating physician. Planned enrollment is 1000 patients in North America (NA) and Europe (EU; France, Germany, Italy, and UK). Results As of June 28, 2013, 111 patients from 63 sites in NA (n=64) and EU (n=47) have been enrolled. Baseline characteristics are summarized in Table 1. Cytogenetics (by FISH) was determined in 51% (n=57) of patients; of these, 16% (n=9) were high risk with del 17p (78%) as the predominant abnormality. Baseline treatment varied by region: of the patients in NA, IMiDs were used in 44% (n=28), PIs in 36% (n=23), and IMiD+PI in 20% (n=13) versus 60% (n=28), 34% (n=16), and 6% (n=3), respectively, in EU. Of the 16% high risk patients and the 25% of patients initially diagnosed at ISS stage III, none received IMiD+PI. The percentage of patients who received only 1 prior regimen at enrollment was 46% (n=26) in the IMiD group, 41% (n=16) in the PI group, and 63% (n=10) in the IMiD+PI group while the percentage of patients who received 3 or more prior regimens was 16% (n=9) in the IMiD group, 36% (n=14) in the PI group, and 6% (n=1) in the IMiD+PI group. Median time from diagnosis to enrollment for patients receiving IMiDs was 43 months, PIs was 42 months, and IMiDs+PIs was 33 months. Conclusion PREAMBLE provides a rich data source for evaluation of clinical, economic, and humanistic outcomes in patients treated for R/R MM. Initial data suggest different treatment patterns between patients in the US and in EU. Continued follow-up and larger sample size may help identify factors associated with different treatment choices and impact on clinical effectiveness, tolerability, resource utilization, and humanistic outcomes in patients treated for R/R MM. Disclosures: Vij: Celgene: Research Funding, Speakers Bureau; Onyx: Research Funding, Speakers Bureau; Millennium: Speakers Bureau; BMS: Honoraria; Lilly: Honoraria. Palumbo:Amgen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen Pharmaceuticals: Consultancy, Honoraria; Millenium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria. Kaya:Millennium: Honoraria, Speakers Bureau. Durie:Millennium: Consultancy; Onyx: Consultancy; Celgene: Consultancy. Cella:BMS: Consultancy. Annemans:BMS: Consultancy. Su:BMS: Employment, Equity Ownership. Mukhopadhyay:BMS: Employment, Equity Ownership. Le:BMS: Employment. Petrucci:Celgene: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria.

scholarly journals Bosutinib Vs Imatinib for Newly Diagnosed Chronic Myeloid Leukemia (CML) in the BFORE Trial: 18 Month Follow-up

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 896-896
Author(s):  
Carlo Gambacorti-Passerini ◽  
Michael W. Deininger ◽  
Michael J. Mauro ◽  
Charles Chuah ◽  
Dong-Wook Kim ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Primary Endpoint ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Employment Equity ◽  
Advisory Committees ◽  
Equity Ownership ◽  
Grade 3

Abstract Introduction: Bosutinib is a potent SRC/ABL tyrosine kinase inhibitor approved for treatment of adults with CML resistant or intolerant to prior therapy. Here we compare the efficacy and safety of first-line bosutinib versus imatinib in patients with chronic phase (CP) CML enrolled in BFORE after ≥18 months of follow-up. Methods: BFORE (NCT02130557) is an ongoing, multinational, open label phase 3 study that randomized 536 patients 1:1 to 400 mg QD bosutinib (n=268) or 400 mg QD imatinib (n=268 [3 not treated]). The prespecified primary endpoint was major molecular response (MMR) rate at 12 months in the modified intent-to-treat (mITT) population, defined as Philadelphia chromosome‒positive (Ph+) patients with e13a2/e14a2 transcripts, and excluding Ph- patients and those with unknown Ph status and/or BCR-ABL transcript type (mITT: BOS, n=246; IM, n=241). Efficacy results refer to the mITT population unless otherwise noted. Results: MMR rate was higher with bosutinib versus imatinib at 18 months (56.9% vs 47.7%; P=0.042). Among all randomized patients (ITT) 18-month MMR rates were higher for bosutinib (56.7% vs 46.6%; P &lt;0.02). Earlier analyses (Table) showed complete cytogenetic response (CCyR) rate by 12 months (77.2% vs 66.4%; P=0.0075) was significantly higher with bosutinib versus imatinib. Rates of BCR-ABL1 transcript ratio ≤10% (International Scale) at 3 months (75.2% vs 57.3%), as well as MR4 at 12 months (20.7% vs 12.0%) and MR4.5 at 12 months (8.1% vs 3.3%), were all higher with bosutinib versus imatinib (all P &lt;0.025). By comparison at 18 months, rates of MR4 (24.4% vs 18.3%) and MR4.5 (11.4% vs 7.1%) were consistent with this trend. Also after ≥18 months follow-up, time to MMR (hazard ratio=1.36, based on cumulative incidence; P=0.0079) and time to CCyR (hazard ratio=1.33; P=0.0049) were shorter for bosutinib (Figure). Cumulative incidence of transformation to accelerated/blast phase disease at 18 months was 2.0% and 2.9% for bosutinb and imatinib, respectively, of which 2 bosutinib and 4 imatinib patients discontinued treatment due to transformation. Additional treatment discontinuations due to suboptimal response/treatment failure occurred in 11 (4.1%) and 35 (13.2%) of bosutinib and imatinib patients, respectively. Dose increases happened in 20% of bosutinib-treated and 31% of imatinib-treated pts There were 2 deaths and 9 deaths in the bosutinib and imatinib arms, respectively. One patient taking bosutinib died within 28 days of last dose, while 4 patients taking imatinib died with that period from last dose. Overall survival at 18 months was 99.6% vs. 96.6% for bosutinib and imatinib groups, respectively. Grade ≥3 diarrhea (8.2% vs 0.8%) and increased alanine (20.9% vs 1.5%) and aspartate (10.1% vs 1.9%) aminotransferase levels were more frequent with bosutinib. Cardiovascular, peripheral vascular, and cerebrovascular events were infrequent in both arms (3.4%, 1.9%, and 0.4% bosutinib vs 0.0%, 1.1%, and 0.8% imatinib; grade ≥3: 1.5%, 0%, and 0.4% vs 0%, 0%, and 0.4%). There were no deaths in the bosutinib arm and 1 death in the imatinib arm due to treatment-emergent vascular events. Treatment discontinuations due to drug-related toxicity occurred in 15.3% and 9.4% of bosutinib and imatinib patients, respectively. Conclusion: After 18 months of follow-up,the MMR benefit seen with bosutinib over imatinib was sustained. These results are in line with observations at 12 months where patients taking bosutinib had significantly higher response rates (primary endpoint) and achieved responses sooner than those on imatinib. Safety data were consistent with the known safety profiles. These results suggest that bosutinib may be an important treatment option for patients with newly diagnosed CP CML. Disclosures Gambacorti-Passerini: Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy. Deininger: Novartis: Consultancy, Research Funding; Pfizer: Consultancy; Celgene: Research Funding; BMS: Consultancy, Research Funding; Gilead: Research Funding; ARIAD: Consultancy; Ariad Pharmaceuticals, Bristol Myers Squibb, CTI BioPharma Corp, Gilead, Incyte, Novartis, Pfizer, Celgene, Blue Print, Galena: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy. Mauro: Bristol-Myers Squibb: Consultancy. Chuah: Avillion: Honoraria; Chiltern: Honoraria; BMS: Honoraria, Other: Travel; Novartis: Honoraria. Kim: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees, Research Funding; Il-Yang: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Milojkovic: Novartis: Consultancy, Honoraria; Incyte: Honoraria, Speakers Bureau; Pfizer: Consultancy, Honoraria; BMS: Consultancy, Honoraria; ARIAD: Consultancy, Honoraria. le Coutre: BMS: Honoraria; Pfizer: Honoraria; Incyte: Honoraria; Novartis: Honoraria, Research Funding; ARIAD: Honoraria. García Gutiérrez: Pfizer: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Incyte: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding. Crescenzo: Pfizer: Employment, Equity Ownership. Leip: Pfizer: Employment, Equity Ownership. Bardy-Bouxin: Pfizer: Employment, Equity Ownership. Hochhaus: Novartis: Research Funding; Pfizer: Research Funding; Incyte: Research Funding; Ariad: Research Funding; MSD: Research Funding; BMS: Research Funding. Brümmendorf: Pfizer: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Cortes: Sun Pharma: Research Funding; ARIAD: Consultancy, Research Funding; Novartis Pharmaceuticals Corporation: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; BMS: Consultancy, Research Funding; ImmunoGen: Consultancy, Research Funding; Teva: Research Funding.

scholarly journals Treatment Patterns and Adherence Among Patients with Myelodysplastic Syndromes Receiving Deferasirox As Iron Chelation Therapy: A Real World Medicare Database Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4759-4759
Author(s):  
Alex Z Fu ◽  
Yanni Hao ◽  
Austin Coe ◽  
Ying Qiu ◽  
Zhiyi Li ◽  
...  
Keyword(s):  
Cardiac Event ◽  
Iron Chelation ◽  
Treatment Patterns ◽  
Event Free Survival ◽  
Employment Equity ◽  
Transfusion Threshold ◽  
Free Survival ◽  
Equity Ownership ◽  
Baseline Characteristics

Abstract Background: Patients with myelodysplastic syndrome (MDS) may present with anemia and become red blood cell (RBC) transfusion dependent (TD), which increases the risk of iron overload (IO). Iron chelation therapy (ICT) treats IO and has been shown to be associated with improved survival and quality of life among TD MDS patients. Deferasirox (DFX) is an oral ICT used to reduce IO in TD MDS patients. This study aims to assess real-world treatment patterns and adherence among MDS patients on Medicare receiving DFX as ICT. Methods: This was a retrospective cohort study using 100% Medicare claims data from 2006-2013. Patients were diagnosed with MDS, identified using ICD-9 codes (238.72-238.76), and entered the study cohort when they met a minimum transfusion threshold of either: 10 consecutive weeks with at least 1 unit of RBC transfusion, or 20 total units of RBC transfusions. Treatment patterns, including discontinuation and treatment changes, were assessed among patients who received DFX as initial ICT and who had ≥180 days of follow-up. Discontinuation was defined as a minimum 45-day treatment gap. Adherence was defined as a medication possession ratio (MPR) ≥ 0.8. Treatment discontinuation, overall survival, acute myeloid leukemia (AML)-free survival, and cardiac event-free survival were compared between adherent and non-adherent patients using Kaplan Meier (KM) survival analysis, as well as Cox regressions controlling for time-dependent ICT use and baseline characteristics. Survivals were estimated as time from cohort entry to the event. Results: Among 6,796 MDS patients who met the minimum transfusion threshold, 591 (8.7%) received ICT. Median weeks of ICT was 15.14 (range=2.29 - 201.43 weeks). 583 (98.6%) initiated with DFX, and 374 DFX patients had a follow-up period of ≥180 days. Of these 374 patients, 213 (57.0%) discontinued DFX treatment within 180 days of initiation. Among the remaining 161 patients, one switched to deferoxamine (DFO), none augmented treatment with DFO, and 160 continued on DFX. The KM-estimated 3-month and 1-year DFX discontinuation rates were 36.5% and 77.4%, respectively, and the average time to discontinuation was 84.4 [Standard Deviation [SD]=48.6] days. Overall, the average 6-month MPR was 0.69 (SD=0.30), and 49.1% of patients were adherent (MPR≥0.8). Adherent patients had similar baseline characteristics compared with non-adherent patients, except that a lower proportion had renal disease (24.2% vs. 38.3%, P<0.01). Patients adherent to DFX had a lower risk of therapy discontinuation (Hazard Ratio=0.07, 95% Confidence Interval, 0.05-0.11) compared with non-adherent patients. Additionally, adherent patients had significantly longer cardiac event-free survival compared with non-adherent patients (1-year rate for cardiac-event/death: 66.1% vs. 76.1%, respectively, P<0.01). There were no statistically significant differences in overall survival and AML-free survival between adherent and non-adherent cohorts. Overall and AML-free survival were longer in the adherent cohort, however this did not reach statistical significance. Conclusions: DFX was the most commonly used ICT among eligible MDS patients. The majority of patients discontinued DFX within 1 year. Adherence to DFX was associated with statistically significant improved cardiac-event free survival. Further analysis on the long-term impact of the duration of chelation is warranted. Disclosures Fu: Novartis Pharmaceuticals Corporation: Consultancy. Hao:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Coe:Novartis Pharmaceuticals Corporation: Employment. Qiu:Novartis Pharmaceutical Corp: Employment, Equity Ownership. Li:Novartis Pharmaceuticals Corporation: Consultancy. Hanna:Novartis Pharmaceuticals Corporation: Consultancy. Tang:Novartis Pharmaceuticals Corporation: Consultancy. Elliott:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Paley:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership.

Sign in / Sign up

Export Citation Format

Share Document