Is Adherence to the American College of Chest Physicians Recommended Anticoagulation Treatment Duration Associated with Different Outcomes Among Patients with Venous Thromboembolism?

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1126-1126 ◽  
Author(s):  
Alex C. Spyropoulos ◽  
Ron Preblick ◽  
Jackie Kwong ◽  
Melissa Lingohr-Smith ◽  
Jay Lin
Keyword(s):  
Venous Thromboembolism ◽  
Treatment Duration ◽  
Bleeding Risk ◽  
Patient Characteristics ◽  
Baseline Period ◽  
Employment Equity ◽  
Minimum Duration ◽  
Study Population ◽  
Equity Ownership

Abstract Introduction: Venous thromboembolism (VTE) represents a major clinical and economic burden. The American College of Chest Physicians (ACCP) Guideline 9th Edition on the treatment of VTE recommends a minimum duration of anticoagulation (AC) therapy depending on patient risk profiles. The objectives of this study were to evaluate the clinical and economic outcomes associated with adherence to the AC treatment duration recommendation among VTE patients in the real world setting. Methods: Adult patients (≥18 years of age) with at least 1 inpatient diagnosis or 2 outpatient diagnoses on two different dates of deep vein thrombosis (DVT) and/or pulmonary embolism (PE), based on ICD-9-CM codes, were identified from the IMS Pharmetrics Plus database during 1/1/2009 through 3/31/2013. The first VTE diagnosis was defined as the index event. Study patients were required to have continuous insurance coverage during the 12 months before (baseline) and after (follow-up) the index event and no prior VTE diagnosis in the baseline period. They were also required to have received at least one outpatient anticoagulant treatment within 30 days of the initial VTE diagnosis with a minimum medication days of supply of 30 days. ACCP recommend that patients with provoked VTE or unprovoked VTE and high bleeding risks receive AC treatment for at least 3 months and that patients with unprovoked VTE and low or moderate bleeding risks or patients with cancer receive AC treatment for at least 6 months. Patient records in the database including ICD-9-CM codes and RIETE bleeding risk scores were used to group patients into 2 cohorts, one comprised of patients who received AC treatment for a duration as recommended by the ACCP (adherent group, AD) and the other comprised of patients who received AC treatment for a duration less than that recommended by the ACCP (non-adherent group, non-AD). Patient demographics and clinical characteristic were evaluated during the baseline period. Healthcare resource utilization, including hospital admissions, outpatient medical services, and prescription drug usage, were measured during the baseline and follow-up periods. VTE recurrence, defined as hospitalization or ER visit with a VTE diagnosis code, was also measured during the follow-up period. Multivariate regression analysis was utilized to compare clinical and economic outcomes of study cohorts while controlling for key patient characteristics. Results: The study population included 81,827 patients with a mean age (standard deviation) of 55.3 (13.8) years. For the index VTE event, 61% had DVT only, 26% had PE only, and 13% had DVT/PE. Of the study population, the minimum ACCP recommended AC treatment durations were 3 and 6 months for 27% (n=22,157) and 73% (n=59,670) of patients, respectively. Among all patients, 74% (n=60,550) received AC therapy for the ACCP recommended duration. The proportion of patients with VTE risks, including recent hospitalization (17% vs. 9%, p<0.001), recent surgery (9% vs. 6%, p<0.001), index diagnosis of PE only (28% vs. 20%, p<0.001), and index diagnosis of DVT/PE (15% vs. 8%, p<0.001) was greater in the AD cohort than in the non-AD cohort. Furthermore, mean Charlson Comorbidity Index score (1.67 vs. 1.59, p<0.001) and RIETE bleeding risk score (RIETE ≥1: 66% vs. 55%, p<0.001) were higher for the AD cohort compared to the non-AD cohort. The most prevalent anticoagulants used for treatment were warfarin (89% vs. 96%, p<0.001) and low molecular weight heparin (58% vs. 59%, p<0.01). After controlling for key patient characteristics, risks for all-cause hospitalization (Odds ratio (OR): 0.80, confidence interval (CI): 0.77-0.83, p<0.001) and VTE recurrence (OR=0.91, CI: 0.86-0.95, p<0.001) were lower among VTE patients in the AD cohort vs. the non-AD cohort, as were differences in all-cause total healthcare payments (-$3,416, p<0.001) and VTE-related healthcare payments (-$2,139, p<0.001) during the follow-up period. Conclusions: Approximately a quarter of the study population with VTE did not receive treatment with AC therapy for the minimum duration as recommended by the ACCP guideline. Patients who did not receive outpatient AC therapy for the recommended duration had more VTE recurrences, utilized more inpatient services, and had higher healthcare costs than patients who received AC therapy for the ACCP recommended duration. Disclosures Spyropoulos: Daiichi Sankyo, Inc.: Consultancy. Preblick:Daiichi Sankyo, Inc.: Employment, Equity Ownership. Kwong:Daiichi Sankyo, Inc.: Employment, Equity Ownership. Lingohr-Smith:Chimerix, Inc.: Consultancy; Bristol-Myers Squibb: Consultancy; Daiichi Sankyo, Inc: Consultancy; Novosys Health: Employment. Lin:Chimerix, Inc.: Consultancy; Daiichi Sankyo, Inc: Consultancy; Bristol-Myers Squibb: Consultancy; Novosys Health: Employment.

Apixaban Reduces Hospitalization In Patients With Venous Thromboembolism: An Analysis Of The AMPLIFY-EXT Trial

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3638-3638 ◽  
Author(s):  
Xianchen Liu ◽  
John Thompson ◽  
Hemant Phatak ◽  
Jack Mardekian ◽  
Anthony R. Porcari ◽  
...  
Keyword(s):  
Placebo Group ◽  
Venous Thromboembolism ◽  
Controlled Trial ◽  
Anticoagulation Therapy ◽  
Cox Proportional Hazards ◽  
Employment Equity ◽  
Double Blind ◽  
Significant Difference ◽  
Equity Ownership

Abstract Introduction Venous thromboembolism (VTE) is associated with a considerable risk for morbidity and recurrence and related hospitalizations. In the Apixaban after the Initial Management of Pulmonary Embolism and Deep Vein Thrombosis with First-Line Therapy-Extended Treatment (AMPLIFY-EXT) trial, a double-blind placebo-controlled trial with 12 months of treatment, two doses of apixaban (2.5 mg and 5 mg, twice daily) versus placebo significantly reduced symptomatic recurrent VTE or all-cause death without increasing the rate of major bleeding among 2,482 VTE patients who had completed 6-12 months of anticoagulation therapy. In this study, the effects of apixaban therapy versus placebo on medical hospitalization during AMPLIFY-EXT trial were evaluated. Methods A total of 2,477 patients who received study drugs were included in the analysis. All-cause hospitalizations during the trial were captured by dedicated case report forms. Outcomes of interest were; rate of hospitalizations and time from randomization to the first hospitalization. Patients were censored at either death, loss to follow-up, or end of study, whichever came first. Effects of treatment with apixaban versus placebo on the rates of hospitalization were assessed using Cox proportional hazards regression models. Results During a mean follow-up of 12.3 months, 138 patients were hospitalized at least once, 62 (7.5%/year) in the placebo group (n=826), 42 (4.8%/year) in the apixaban 2.5 mg group (n=840), and 34 (4.0%/year) in the apixaban 5 mg group (n=811). Compared with placebo, apixaban 2.5 mg [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.44–0.96; p=0.030] and 5 mg (HR 0.54, 95%CI 0.36–0.83, p=0.004) were both associated with significant reduction in hospitalization. There was no significant difference in hospitalizations between the 2 doses of apixaban (5 mg vs. 2.5 mg: HR 0.84, 95%CI 0.53–1.32, p=0 .445). The mean time to first hospitalization was 153.7 days in the placebo group, 196.9 days in the apixaban 2.5 mg group, and 202.4 days in the apixaban 5 mg group (Figure). Conclusions Extended anticoagulation with apixaban at either a dose of 5 mg or 2.5 mg significantly reduced the risk of hospitalization, possibly due to the reduction in VTE recurrence. Disclosures: Liu: Pfizer: Employment, Equity Ownership. Thompson:Pfizer: Employment, Equity Ownership. Phatak:BMS: Employment, Equity Ownership. Mardekian:Pfizer: Employment, Equity Ownership. Porcari:Pfizer: Employment, Equity Ownership. Johnson:Pfizer: Employment, Equity Ownership.

Follow-up of Real Life Treated Multiple Myeloma Patients: Response, Disease Progression and Overall Survival,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3937-3937
Author(s):  
Hareth Nahi ◽  
Johan Liwing ◽  
Katarina Uttervall ◽  
Johan Andreasson ◽  
Astrid Gruber ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Practice ◽  
Real Life ◽  
M Protein ◽  
Novel Agents ◽  
Response Distribution ◽  
Employment Equity ◽  
Study Population ◽  
Equity Ownership

Abstract Abstract 3937 Treatment results in clinical practice and in real life can be different from each other. Therefore, evaluating real life outcomes in Multiple Myeloma (MM) patients in order to understand treatment outcome in clinical practice is very important. All patients diagnosed with MM and treated between Jan 2000 and Jul 2010 at Karolinska University Hospital, Huddinge and Södersjukhuset were included. Furthermore, all diagnosed patients between Jan 2005 and Jul 2010 at Karlolinska University Hopital, Solna were included. At diagnosis data regarding age, gender, type of myeloma and skeleton destruction as well as Ca, Hb, β2-microglobelin, albumin and creatinine were collected. For each treatment line, drugs given and specific start and stop dates for each drug were collected. Serum and urine M-protein was collected at baseline and each time the measurement differed from the previous. Near complete response (nCR) was defined as an immeasurable M-protein in the blood and urine by standard electrophoresis but not always confirmed by immunofixation since it was not required in clinical practice. Partial response (PR) was defined as a 50% reduction in M-protein. No response (NR) was defined as less than 50% reduction of M-protein. Progress was considered when M-protein increased with ≥ 25%. Novel agents were defined as bortezomib, lenalidomide and thalidomide. In the total population n=674, 89 (13%) patients were excluded due to non treatment demanding disease or plasmacytoma without MM diagnosis setting the study population to n=585. The median follow up of the study population was 815 days. The median age in the study population was 68 years and 45% were women. High dose treatment (HDT) was given to 214 (37%) patients. The median age in the HDT population was 58 years and 34% were women. The median age in the non-HDT population was 75 years and 51% was women. The median number of given treatment lines was 2. The proportion of patients receiving more treatment lines were declining rapidly with the number of received lines of therapy. The response distribution for the entire population nCR/PR/NR was 27/41/32 in 1st line, 18/34/48 in 2nd line. In the HDT population the same response distribution was 50/38/12 in 1st line and 28/38/34 in 2nd line. In the non-HDT population the response distribution was 14/43/43 in 1st line and 12/33/55 in 2nd line. The depth of the responses was significantly dependent on the line of therapy. Responses were significantly better in the HDT population vs. the non-HDT population in the first two treatment lines. There seems to be a correlation between the responses in 1st and 2nd line in the entire population. Improving the responses in 2nd line compared to 1st line seems not very likely. Statistical analysis shows that the non-HDT patients receiving novel agents in 1st line had a significantly higher probability of achieving nCR, 25% vs 9%.The same statistical difference was seen in the HDT patients with nCR rates of 65% vs 47%. The median TTP/TTNT for the study population was 309/381 days in the 1st line and 182/210 in 2nd line. In the HDT population the TTP/TTNT was 538/639 days in 1st line and 199/257 in 2nd line. In the non-HDT population the TTP/TTNT was 244/295 days in 1st line and 177/193 in 2nd line. In the HDT population both the TTP and the TTNT in the 1st line were significantly better than in the non-HDT population with no difference in the 2nd line. There was a significant trend of increasing TTP/TTNT in 1st line depending on the increased depth of the response. Statistical analysis showed that the use of novel agents in 1st line predicted a longer TTP for the non-HDT population. Median OS was 4.3 years 95% CI [3.9;5.0] with 53% censored. HDT patients had a significant longer median OS 6.3 years 95% CI [5.4;8.5] than the non-HDT patients OS 3.0 years 95% CI [2.2;3.6]. The median OS for non-HDT patients with 1st line best response nCR was 4.9 years, PR 3.3 years and NR 1.5 years. Kaplan-Mayer analysis shows that use of novel agents in the 1st line predicted a longer OS, median 5.1 years vs. 4.1 years. Patients receiving 2nd and 3rd line treatment were declining rapidly. To get a good response in 1st line increases the likelihood of having a good response in 2nd line. Receiving an nCR in 1st line seems to be very important and this study confirms the prognostic impact of achieving at least nCR. The use of novel agents improves the outcome for patients in clinical practice. Disclosures: Liwing: Janssen-Cilag: Employment, Equity Ownership. Näsman:Janssen-CIlag: Consultancy. Aschan:Janssen-Cilag: Employment, Equity Ownership.

Overall Safety and Treatment Duration in Lenalidomide (LEN)-, Thalidomide (THAL)-, and Bortezomib (BORT)-Treated Patients (Pts) within the European Post-Approval Safety Study (EU PASS) of Relapsed/Refractory Multiple Myeloma (RRMM)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4068-4068
Author(s):  
Barbara Gamberi ◽  
Charalampia Kyriakou ◽  
John Ashcroft ◽  
Miguel T. Hernandez ◽  
Jo Caers ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Disease Progression ◽  
Treatment Duration ◽  
Treatment Discontinuation ◽  
Study Entry ◽  
Current Clinical Practice ◽  
Employment Equity ◽  
Equity Ownership ◽  
Grade 3

Abstract Abstract 4068 Background: The efficacy and tolerability of LEN in pts with RRMM has been demonstrated in 2 large, randomized, phase 3 studies (MM-009/010). BORT and THAL have also been shown to be effective for RRMM treatment. While many studies have described the safety of antimyeloma drugs in the clinical trial setting, few have addressed the issue of tolerability in current clinical practice. Aims: In this study, we compared the incidence of adverse events (AEs) of special interest, such as neutropenia, thrombocytopenia, venous thromboembolism (VTE), peripheral neuropathy (PN) and second primary malignancies (SPM) in pts treated with LEN versus other antimyeloma therapies for RRMM in current clinical practice. Additionally, duration of treatment was assessed in the context of therapy received just prior to study entry. Methods: In this post-approval, observational, non-interventional, EU PASS study, pts with RRMM were enrolled into either the LEN cohort (LEN-based therapy) or the background cohort (all non-LEN based therapies) at the investigators' discretion. Thromboprophylaxis was per local standard practice. AEs were graded according to NCI-CTCAE v3.0. Assessments for SPM were to be conducted up to 36 months (mos) after treatment discontinuation. Results: As of May 2012, overall median follow-up was 5.7 mos (range 0.02–39.8), (6.4 mos LEN, 5.7 mos THAL, 4.9 mos BORT). There were 3107 pts across 268 institutions in 17 European countries enrolled: 2141 received LEN, 751 received BORT, 110 received THAL, and 105 received other therapies or had incomplete information on the treatment arm. 127 pts from the background cohort crossed over following the physician's decision to initiate LEN treatment as a subsequent therapy. Median age was 70 years (range, 25–95) and 54% were male. Most pts (65%) had good performance status (ECOG score 0–1); 17% had an ECOG score of 2–4. Median overall number of prior therapies was 2 (range, 0–6) and this was consistent across the cohorts: 53% had 2 prior therapies and 21% had ≥3. Baseline characteristics were similar between groups. Overall, 1397 (45.0%) had a grade 3–4 AE. Grade 3–4 neutropenia occurred in 14%, 4%, and 5% of pts in the LEN, BORT, and THAL groups, respectively. Grade 3–4 thrombocytopenia developed in 8%, 9%, and 3% of pts, respectively. In the LEN group, only 7% of pts (1% grade 3–4) reported PN (4% newly occurring) while receiving LEN (despite 36% of pts presenting with PN at baseline) compared with 28% (5% grade 3–4) with BORT (22% PN at baseline) and 16% (2% grade 3–4) with THAL (19% PN at baseline). Grade 3–4 VTE developed in 2.7% of pts in the LEN group, 0.7% in the BORT group, and 1.8% in the THAL group. Overall treatment discontinuation rates (including disease progression) were 70%, 85%, and 86% in the LEN, BORT, and THAL groups, respectively, with nearly identical discontinuation rates due to AEs (17%) in each group, and disease progression rates of 15–20%. SPM incidence was ≤1% overall and invasive SPM incidence rate per 100 patient-years (95% CI) was 1.4 (0.94 –2.09) at a median follow-up of 10 mos and was comparable across the cohorts. Incidence of death during the study was comparable with all treatments (LEN 6%, BORT 4%, and THAL 5%); the incidence of treatment-related AEs leading to death was 1.4%, 1.2% and 0.9%, respectively. The median treatment duration was 4.6 mos in the overall population; 5.4 mos in pts treated with LEN, 3.7 mos in pts treated with BORT, and 4.6 mos in pts treated with THAL. At a 5.7 mos median follow-up, 19.9%, 2.0%, and 14.5% of pts in the LEN, BORT, and THAL arms had a treatment duration of >12 mos; and 2.2%, 0.3%, and 0.9% had a treatment duration of >24 mos, respectively. In an analysis of study treatment by last therapy prior to study entry, patients receiving THAL or BORT followed by LEN had a median on-study treatment duration of 5.7 mos and 5.2 mos, respectively, independent of the line of treatment. In comparison, pts receiving THAL or BORT followed by BORT had lower median study treatment duration of 3.7 mos and 3.8 mos, respectively. Conclusions: Results of this non-interventional, observational study show that AEs were similar with all treatments except for higher rates of neutropenia and lower rates of PN with LEN, compared with BORT or THAL. Despite the current short overall follow-up, treatment duration within the LEN, BORT, or THAL groups appears to be unaffected by prior treatment received but was longer for LEN when compared with BORT or THAL. Disclosures: Küenburg: Celgene Corporation: Employment, Equity Ownership. Rosettani:Celgene Corporation: Employment, Equity Ownership. Ryder-Smith:Celgene Corporation: Employment, Equity Ownership.

Bleeding Incidence Among Patients With Venous Thromboembolism: A Large US Insurance Database Analysis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2916-2916 ◽  
Author(s):  
Xianchen Liu ◽  
Lin Xie ◽  
Hemant Phatak ◽  
Jack Mardekian ◽  
Wilson Tan ◽  
...  
Keyword(s):  
Heart Disease ◽  
Venous Thromboembolism ◽  
Major Bleeding ◽  
Research Funding ◽  
Index Date ◽  
Bleeding Risk ◽  
Employment Equity ◽  
History Of ◽  
Equity Ownership ◽  
Insurance Database

Abstract Introduction It is crucial to assess clinical benefit and bleeding risk when selecting an anticoagulant for patients with venous thromboembolism (VTE). This study examined the incidence of major bleeding and non-major bleeding and clinical predictors of major bleeding among patients with VTE in the usual clinical practice setting. Methods VTE patients aged ≥18 years were identified from the Truven Health MarketScan commercial or Medicare supplemental insurance database. Index date was defined as the first VTE diagnosis between 07/01/2006 – 12/31/2011. Patients were required to have ≥2 VTE outpatient diagnoses within a 3-week window or have 1 VTE diagnosis in an inpatient setting, have a continuous health plan enrollment for 6 months prior to the index date (baseline), and have no VTE diagnosis in the baseline period. Major bleeding was defined as any bleeding that resulted in hospitalization or blood transfusion; all other bleeds were non-major bleeding. Patients were followed until major bleeding/non-major bleeding, death, disenrollment, or end of study. Multivariate Cox regression was used to examine factors associated with major bleeding. Results Of 267,655 eligible patients, 182,972 patients were with deep vein thrombosis (DVT) only (68.4%), 69,169 with pulmonary embolism (PE) only (25.8%); and 15,514 with both (5.8%). Mean age was 61.5 years, and 53.1% were female. Mean follow-up period was 17.3 months (median=12.1). The annual incidence of major bleeding and non-major bleeding were 3.9% and 20.1%, respectively. The median time to major bleeding from index VTE diagnosis was 2.2 months. Major risk factors at baseline for major bleeding (Risk increase>20%) were history of major bleeding (HR=10.78, 95%CI=10.30-11.28) and non-major bleeding (HR=1.61, 95%CI=1.54-1.68), chemotherapy (HR=1.27, 95%CI=1.20-1.35), age ≥65 vs.≤40 years (HR=1.27, 95%CI=1.18-1.37), alcohol abuse (HR=1.26, 95%CI=1.16-1.38), cancer (HR=1.25, 95%CI=1.19-1.31), and heart disease (HR=1.23, 95%CI=1.18-1.28) (Table). Baseline hormone therapy (HR=0.74, 95%CI=0.68-0.80) and pregnancy (HR=0.59, 95%CI=0.46-0.74) were associated with reduced risk for major bleeding. Conclusions Major and non-major bleeding were common in patients with VTE. Multiple factors, especially history of bleeding, age≥65 years, alcohol abuse, cancer and heart disease, were associated with increased risk for major bleeding. Further research needs to examine bleeding risk associated with anticoagulant therapy. Disclosures: Liu: Pfizer: Employment, Equity Ownership. Xie:StatInMed: Employment, Research Funding. Phatak:BMS: Employment, Equity Ownership. Mardekian:Pfizer: Employment, Equity Ownership. Tan:Pfizer: Employment, Equity Ownership. Baser:StatInMed: Employment, Research Funding. Ramacciotti:BMS: Employment, Equity Ownership.

scholarly journals Progression-Free Survival in Third-Line Treatment of Relapsed/Refractory Multiple Myeloma Among Patients with Who Have Received Prior Bortezomib and Immunomodulatory Drugs

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3311-3311
Author(s):  
Sundar Jagannath ◽  
Anuja Roy ◽  
Jonathan K Kish ◽  
Denise Globe ◽  
Orsolya Lunacsek ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Standard Of Care ◽  
Employment Equity ◽  
Free Survival ◽  
Treatment Regimens ◽  
Risk Of Progression ◽  
Study Population ◽  
Equity Ownership ◽  
Immunomodulatory Drug

Abstract Background: There are limited data on real-world treatment outcomes for novel agents used in the treatment of relapsed/refractory multiple myeloma (RRMM). These data are particularly important for patients who have already received bortezomib (BTZ) and an immunomodulatory drug (IMiD) given the lack of a standard of care in 3rd line and the costs of novel therapies including lenalidomide (LEN), carfilzomib (CFZ) and pomalidomide (POM). Methods: Data including patient and disease characteristics, treatment information and mortality data were collected from electronic medical records. RRMM patients diagnosed between 01/2007-08/2014 having received at least three treatment regimens (not including maintenance) were selected from the International Oncology Network (ION) database. Treatment regimens were aggregated into 8 mutually exclusive categories. Progression-free survival (PFS), based on physician reported date of progression, was calculated by treatment regimen overall and for the subgroup of patients who had prior BTZ and IMiD exposure. A multivariate proportional hazard model was used to estimate the risk of progression or death in the subgroup adjusting for age, gender, race, year of diagnosis, ISS stage, presence of cytogenetic abnormality, immunoglobulin type, receipt of stem-cell transplant (SCT), ECOG status and comorbidities at diagnosis. Results: There were 391 patients that met inclusion criteria. Mean age at diagnosis was 68 years, 46.9% being ISS III and 55.5% were classified as IgG. Median duration of follow-up was 36.1 months with 45% of patients being deceased by the end of follow-up. SCT information was available for 218 patients: 25.2% were deemed ineligible, 46.8% received an SCT and 28% of eligible patients had no evidence of receiving a SCT. BTZ and an IMiD were received by 239/391 (61.1%) patients prior to 3rd line. PFS in 3rd -line for the overall study population and the subgroup are presented in Table 1. For the subgroup, the median PFS in 3rd-line among regimens with at least 10 patient was: BTZ monotherapy ± non-IMiD - 7.3 months; LEN monotherapy or ± non-proteasome inhibitor (PI) - 4.9 months; BTZ + IMiD - 7.3 months; CFZ monotherapy ± IMiD - 3.7 months; and POM monotherapy ± PI - 5.8 months. Although not statistically significant, risk of progression or death after adjustment for baseline demographic and clinical characteristics was lower for BTZ + IMiD and other chemotherapies and higher for LEN monotherapy or ± non-PI, CFZ monotherapy ± IMiD and POM monotherapy ± PI compared to BTZ mono ± non-IMID (Table 1). Conclusions: These data are the first recent real-world treatment outcomes in RRMM. For BTZ-, LEN-, and POM-containing regimens, PFS was non-significantly shorter in 3rd-line for those patients with prior BTZ and IMiD treatment compared to the overall study population. For the subgroup, the results of the multivariate proportional hazards model showed no significant difference in the risk of progression or death in 3rd-line for patients with prior BTZ and IMiD therapy compared to other treatment regimens. As such, there remains a significant unmet need for novel treatment regimens which significantly improve PFS for the subgroup of patients who have received prior treatment with both BTZ and an IMiD. Table 1. Overall Patients with prior BTZ and IMiD¥ 3rd - Line Treatment Regimen N PFS (95% CI) N PFS (95% CI) HR p-value BTZ mono ± non-IMID 128 9.1 (7.1 - 10.9) 69 7.3 (4.2 - 10.8) REF - LEN mono ± non-PI 88 7.0 (4.7 - 10.6) 45 4.9 (3.0 - 8.6) 1.23 0.43 BTZ + IMID (thalidomide or lenalidomide) 59 9.4 (5.3 - 12.3) 39 7.3 (5.0 - 15.0) 0.84 0.55 THAL mono ± non-PI 12 8.5 (1.4 - 16.4) 7 9.8 (0.1 - 50.4) 0.94 0.89 MEL mono ± non-IMiD, non-PI 19 8.3 (3.4 - 13.2) 7 3.4 (0.6 - NR) 1.16 0.78 MEL + THAL 5 25.2 (0.7 29.4) 4 25.2 (0.7 - 29.4) * * CFZ mono ±IMID / Other † 37 3.6 (2.6 - 8.4) 34 3.7 (2.8 - 8.4) 1.13 0.68 POM mono ± PI / Other 17 9.6 (1.6-13.8) 15 5.8 (1.4 - 13.8) 1.18 0.68 Other Chemotherapies 26 5.6 (2.1 -13.3) 19 7.9 (1.9 - 14.0) 0.95 0.87 ¥ Steroids (dexamethasone or prednisone) may have been given in conjunction with any of the therapies per usual standard of care. † Includes patients treated with combination CFZ + POM. * Patients combined with "Other Chemotherapies" in model. Key: BTZ - bortezomib; CI - confidence interval; CFZ - carfilzomib; IMiD - immunomodulatory drug; LEN - lenalidomide; MEL - melphalan; NR - not reached; PI - proteasome inhibitor; POM - pomalidomide; THAL - thalidomide. Disclosures Jagannath: Janssen: Honoraria; Celgene: Honoraria; Merck: Honoraria; Bristol Myers Squibb: Honoraria; Novartis: Honoraria. Roy:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Kish:Xcenda LLC: Employment. Globe:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Lunacsek:Xcenda LLC: Employment. Eaddy:Xcenda LLc: Employment. Kuriakose:Novartis: Employment, Equity Ownership. Willey:Xcenda LLc: Employment. Siegel:Celgene Corporation: Consultancy, Speakers Bureau; Amgen: Speakers Bureau; Takeda: Speakers Bureau; Novartis: Speakers Bureau; Merck: Speakers Bureau.

scholarly journals Benefit-Risk of Ponatinib Vs. Bosutinib in Chronic Phase Chronic Myeloid Leukemia (CP-CML) Patients Who Failed Two Prior Tyrosine Kinase Inhibitors (TKIs): An Indirect Comparison

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3154-3154 ◽  
Author(s):  
Moshe Yair Levy ◽  
Lisa J McGarry ◽  
Hui Huang ◽  
Stephanie Lustgarten ◽  
Christopher Nieset ◽  
...  
Keyword(s):  
Treatment Duration ◽  
Indirect Comparison ◽  
Clinical Trial Data ◽  
Study Drug ◽  
Advisory Board ◽  
Trial Data ◽  
Employment Equity ◽  
Equity Ownership ◽  
Surrogate Measures

Abstract INTRODUCTION: Prior to the introduction of bosutinib and ponatinib, CP-CML patients who had failed 2 prior lines of TKI had limited treatment options with generally poor treatment response and outcomes. These newer TKIs are important additions to the treatment armamentarium, but the optimal choice of 3rd-line (3L) treatment has not been established. Clinical trials in patients who have failed 2 previous lines of TKI suggest ponatinib is more efficacious than bosutinib, but with a less favorable side-effect profile, requiring a potential benefit-risk tradeoff in treatment choice. Comparison of overall benefit-risk from available clinical trial data is challenging due to single- arm designs, low overall mortality, disparate impact of characteristic side-effects, and the likely crossover/sequential use of alternative TKIs among patients discontinuing therapy. We therefore examined efficacy outcomes previously validated as predictors of long-term survival, as well as treatment duration and reason for study drug discontinuation, as surrogates for overall benefit-risk in 3L CP-CML patients treated with ponatinib vs. bosutinib. METHODS: Using clinical trial data for 3L CP-CML from Khoury 2012 for bosutinib and PACE (unpublished) for ponatinib, we examined efficacy outcomes including major (MCyR) and complete (CCyR) cytogenetic response, and major molecular response (MMR), durability of response, duration on therapy and reasons for discontinuation among patients treated with ponatinib vs. bosutinib after failing 2 prior TKIs. Outcomes were evaluated at similar follow-up time points: median 28.5 (range 0.3-56.2) months bosutinib; median 30.5 (0.2-39.8) months ponatinib. Efficacy outcomes were defined such that patients were required to demonstrate improvement relative to baseline to be counted as responders. Investigator-reported primary reason for discontinuation was examined and considered caused by treatment failure if due to death, disease progression or unsatisfactory response. RESULTS: Treatment response was higher for 3L CP-CML patients treated with ponatinib (N=98) than with bosutinib (N=118) across all measures. MCyR was achieved by 67% of ponatinib vs. 32% of bosutinib patients, CCyR by 56% of ponatinib vs. 24% of bosutinib patients, and MMR by 42% vs. 15%. Patients who received ponatinib experienced more durable responses with 93% of the ponatinib patients who achieved MCyR estimated to retain response after 2 years vs. 59% of the bosutinib patients who achieved this response level. After approximately 2.5 years of follow up, less than one-third (29%) of bosutinib patients remained on study drug vs. the majority (57%) of ponatinib patients (Figure). The median treatment duration was substantially shorter for bosutinib vs. ponatinib, with patients remaining on ponatinib therapy more than 3.5 times as long as on bosutinib (Figure). The majority of 3L bosutinib patients that discontinued did so due to treatment failure (58.3% of the patients who discontinued), while less than one-quarter (23.8%) of ponatinib patients who discontinued did so due to failure. The impact of AEs on discontinuation was similar: about 1 in 5 patients on both therapies discontinued due to AEs. CONCLUSIONS: Our indirect comparison using a variety of surrogate measures provides strong evidence of superior efficacy and durability of response with ponatinib vs. bosutinib in 3L CP-CML patients; the higher proportion of ponatinib patients continuing on therapy and the longer duration of therapy also suggest patients experience better overall response and tolerability outcomes with ponatinib vs. bosutinib. Based on the surrogate measures of patient benefit- risk examined in this analysis, ponatinib appears to provide a net overall benefit vs. bosutinib in 3L CP-CML patients. Figure 1 Figure 1. Disclosures Levy: ARIAD Pharmaceuticals, Inc.: Consultancy, This ASH abstract publication value, advisory board speaking engagement, advisory board participation Other. McGarry:ARIAD Pharmaceuticals, Inc.: Employment, Equity Ownership. Huang:ARIAD Pharmaceuticals, Inc.: Employment, Equity Ownership. Lustgarten:ARIAD Pharmaceuticals Inc: Employment, Equity Ownership. Nieset:ARIAD Pharmaceuticals, Inc.: Employment, Equity Ownership. Haluska:ARIAD Pharmaceuticals, Inc.: Employment, Equity Ownership.

scholarly journals Daratumumab (DARA) Maintenance Therapy Improves Depth of Response and Results in Durable Progression-Free Survival (PFS) Following Dara Plus Cyclophosphamide, Bortezomib, and Dexamethasone (CyBorD) Induction Therapy in Multiple Myeloma (MM): Update of the Lyra Study

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 863-863 ◽  
Author(s):  
Robert M. Rifkin ◽  
Jason M. Melear ◽  
Edward Faber ◽  
William I. Bensinger ◽  
John M Burke ◽  
...  
Keyword(s):  
Stem Cell ◽  
Board Of Directors ◽  
Induction Therapy ◽  
Safety Profile ◽  
Employment Equity ◽  
Advisory Committees ◽  
Depth Of Response ◽  
Equity Ownership ◽  
Grade 3

Background: DARA, a human IgGκ monoclonal antibody targeting CD38, is approved in combination with bortezomib, melphalan, and prednisone (VMP) and bortezomib and dexamethasone (Vd) for newly diagnosed MM (NDMM) and relapsed MM (RMM), respectively. CyBorD is a commonly used immunomodulatory drug-sparing regimen for MM. In the LYRA (NCT02951819) study, DARA plus CyBorD (DARA-CyBorD) demonstrated efficacy and a tolerable safety profile at the end of induction. Here, we present updated findings examining the effect of monthly DARA maintenance on the efficacy and safety of DARA-CyBorD in NDMM and RMM. Methods: LYRA is an ongoing, single-arm, open-label, phase 2 study conducted at US community oncology centers. Patients (pts) were aged ≥18 years with documented MM per IMWG criteria, an ECOG performance score (PS) of 0-2, and ≤1 prior line of therapy. Pts received 4-8 induction cycles of DARA-CyBorD (cyclophosphamide 300 mg/m2 PO on Days 1, 8, 15, and 22; bortezomib 1.5 mg/m2 SC on Days 1, 8, and 15; and dexamethasone 40 mg PO or IV weekly [qw]) every 28 days. DARA was given at 8 mg/kg IV on Days 1 and 2 of C1, 16 mg/kg qw from C1D8 through C2, 16 mg/kg q2w for C3-6, and 16 mg/kg q4w for C7-8. After induction, eligible pts could undergo autologous stem cell transplantation (ASCT). All pts received up to 12 maintenance cycles with DARA 16 mg/kg IV q4w. Results: A total of 101 (87 NDMM, 14 RMM) pts were enrolled; 100 (86 NDMM, 14 RMM) pts received ≥1 treatment dose. Median age was 63 years; most pts were white (81%), male (64%), had ECOG PS 0-1 (94%) and had IgG (57%) MM; 36% of pts had high cytogenetic risk, defined as a del(17p), t(4:14) or t(14;16) abnormality. NDMM and RMM pts received a median of 6 and 8 cycles, respectively, of induction therapy. Thirty-nine NDMM pts and 1 RMM pt underwent ASCT. Fifty percent of pts received plerixafor; median stem cell yield for NDMM pts was 6.2 x 106 (range 2-15 x 106) CD34+ cells/kg. A total of 85 (75 NDMM, 10 RMM) pts received ≥1 dose of maintenance treatment; 63 (56 NDMM, 7 RMM) pts have received all 12 maintenance cycles. In NDMM pts, ORR was 87%, with 64% ≥VGPR and 12% ≥CR, by the end of induction. By the end of maintenance, ORR, ≥VGPR and ≥CR rates were 97%, 82% and 51% in NDMM pts who underwent ASCT and 83%, 70% and 30% in NDMM pts who did not receive ASCT. In RMM pts, ORR, ≥VGPR and ≥CR rates were 79%, 71% and 29% by the end of induction and 86%, 71% and 64% by the end of maintenance. At a median follow up of 24.8 mo in NDMM pts and 26.6 mo in RMM pts, median duration of response was not reached (NR). Median PFS (Figure) was NR in NDMM pts, regardless of transplant status, and was 21.7 mo in RMM pts; median OS was NR in NDMM pts and was 30.1 mo in RMM pts. In NDMM pts the 24-mo PFS rate was 89% in pts who underwent ASCT and 72% in pts who did not receive ASCT. The 24-mo OS rate was 90% for NDMM pts. In RMM pts, the 24-mo PFS and OS rates were 48% and 64%, respectively. All treated pts had ≥1 TEAE. Common TEAEs (≥25%) included fatigue, nausea, cough, diarrhea, upper respiratory tract infection, back pain, vomiting, insomnia, dyspnea, constipation, and headache. Grade 3/4 TEAEs were reported in 62% of pts; the most common (≥10%) was neutropenia (14%). Serious TEAEs occurred in 33% of pts; the most common (&gt;2%) were pneumonia, atrial fibrillation and pulmonary embolism. TEAEs led to permanent treatment discontinuation in 7% of pts, with 2% related to treatment. TEAEs resulted in death in 2 pts (nephrotic syndrome, sudden death); both unrelated to treatment. Infusion reactions (IRs) occurred in 56% of pts including grades 1-2 in 52% of pts, grade 3 in 3% of pts and grade 4 in 1% of pts. Most common (&gt;5%) IRs were chills, cough, dyspnea, nausea, pruritus, flushing and nasal congestion. Conclusion: Maintenance with DARA monotherapy for 12 mo increased the &gt;CR rate in NDMM and RMM pts, consistent with observations in prior studies that longer DARA treatment improves depth of response. Importantly, the increase in ≥CR rate was associated with durable PFS and OS. The 24-mo PFS rates in NDMM and RMM pts compare favorably with results for DARA-VMP and DARA-Vd in NDMM and RRMM, respectively. Safety profile was consistent with previous reports of DARA, with no new safety concerns observed with longer follow-up. These data indicate that DARA-CyBorD is a safe, effective MM treatment and that DARA maintenance increases depth of response and achieves durable remissions. Disclosures Rifkin: Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Melear:Texas Oncology: Employment; DARA: Speakers Bureau. Faber:Cardinal Health: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Bensinger:Amgen, Celgene: Other: Personal Fees, Research Funding, Speakers Bureau; Takeda, Janssen: Speakers Bureau; Sanofi, Seattle Genetics, Merck, Karyopharm: Other: Grant. Burke:Gilead: Consultancy; Celgene: Consultancy; Roche/Genentech: Consultancy. Narang:Celgene: Speakers Bureau. Stevens:Astellas: Consultancy. Gunawardena:Janssen: Employment, Equity Ownership. Lutska:Janssen: Employment. Qi:Janssen: Employment. Ukropec:Janssen: Employment, Equity Ownership. Qi:Janssen: Employment. Lin:Janssen: Employment, Equity Ownership. Yimer:Amgen: Consultancy; Clovis Oncology: Equity Ownership; Puma Biotechnology: Equity Ownership; Celgene: Honoraria; Seattle Genetics: Honoraria; Janssen: Speakers Bureau; AstraZeneca: Speakers Bureau.

scholarly journals Health Resource Utilization and Costs Associated with the Use of Obinutuzumab-Based Regimens Are Similar to Rituximab-Based Regimens for the First-Line Treatment of Follicular Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4721-4721
Author(s):  
Tu My To ◽  
Keith L. Dawson ◽  
Anthony S Masaquel ◽  
Arpamas Seetasith
Keyword(s):  
Drug Treatment ◽  
Follicular Lymphoma ◽  
Real World ◽  
Specific Drug ◽  
First Line ◽  
Employment Equity ◽  
Total Cost ◽  
Claims Database ◽  
Equity Ownership

Introduction: Obinutuzumab (GA101; G), a fully humanized, glycoengineered, type II anti-CD20 monoclonal antibody, is approved in the US for the first-line (1L) treatment of follicular lymphoma (FL). Despite the superior efficacy of G plus chemotherapy (G-chemo) versus rituximab (R) plus chemotherapy (R-chemo) in patients with previously untreated FL demonstrated in the Phase III, randomized GALLIUM study (NCT01332968; Marcus et al. N Engl J Med 2017), information on healthcare resource use (HRU) and real-world costs with G in previously untreated FL patients is limited. The aim of this retrospective cohort study was to examine HRU and costs for G-based and R-based therapies for the 1L treatment of FL using a US claims database. Methods: The data source for this study was the PharMetrics Plus Commercial Claims database. Adult patients (≥18 years) diagnosed with FL between February 1, 2015 and September 30, 2018 and who began any treatment for FL between February 1, 2016 and September 30, 2018 were included. The first FL treatment date within this selection window was denoted the index date. Patients were required to have ≥12 months of pre-index and ≥3 months of post-index continuous study enrolment, and to have at least one FL diagnosis on or during the 12-month pre-index period. Patients with FL treatment during the 12-month pre-index period were excluded in order to select only previously untreated patients. HRU and cost data during the 1L treatment period were descriptive and categorized by HRU category. Costs are in 2018 US dollars ($) and standardized as per patient per month (PPPM) costs. FL treatment determination was based on National Comprehensive Cancer Network guidelines. Results: A total of 1584 FL patients with ≥3 months follow up were analyzed. Overall, 26 patients received G-chemo (any combination) as their 1L treatment, 208 patients received R-CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), 391 patients received R-Benda (bendamustine) and 17 patients received R-CVP (cyclophosphamide, vincristine, prednisone); the remaining 942 patients received other regimens (predominantly other R combinations). Data are reported for those patients who received G-chemo, R-CHOP, R-Benda or R-CVP as 1L therapy (n=642; 281 females, 361 males). Baseline patient characteristics were similar for most variables across treatment groups. Mean (standard deviation [SD]) age was 56.9 (9.7) years and all patients had a Charlson Comorbidity Index (CCI) of ≥2 (mean [SD]: 2.9 [1.9]). Mean (SD) patient follow-up was 14.1 (8.0) months and mean (SD) duration of 1L treatment was 7.0 (5.1) months. A summary of all-cause HRU in patients receiving 1L treatment is provided by treatment category (Figure 1A). The proportion of patients with at least one hospitalization was highest with R-CHOP (23.6%). The proportion of patients with at least one emergency room (ER) visit was highest with R-Benda (29.4%). Mean (SD) total all-cause healthcare costs PPPM during 1L treatment were comparable among G-chemo, R-CHOP and R-Benda (Figure 1B) and lowest with R-CVP ($17,874 [$13,465]). Medical costs (mean [SD]) were highest for R-Benda ($27,716 [$19,610] PPPM) and lowest for R-CVP ($17,373 [$12,908] PPPM). G-chemo was associated with the lowest pharmacy costs ($76 [$107] PPPM) (Figure 1B). Mean (SD) total cost of FL drug treatment PPPM was $16,028 ($9,942) for G-chemo, $11,684 ($6,122) for R-CHOP and $12,108 ($8,794) for R-CVP. Mean (SD) total cost of FL drug treatment PPPM was highest with R-Benda ($21,263 [$15,328]). G-specific drug costs PPPM ($9,643 [$6,071]) were similar to R-specific drug costs ($9,992 [$5,234] R-CHOP; $9,083 [$5,859] R-Benda; and $10,702 [$7,717] R-CVP). Conclusions: Our results depict real-world HRU and costs associated with G and commonly used 1L regimens for FL. In this setting, HRU and costs associated with G-chemo were comparable with R-chemo, supporting the use of G-chemo as a treatment option for patients with previously untreated FL. The study findings are limited by the small sample size of the G-chemo patient cohort (n=26) and short follow-up; to address this, an updated analysis incorporating a larger number of patients is planned. Disclosures To: Genentech, Inc.: Employment, Equity Ownership. Dawson:Roche/Genentech: Equity Ownership; Genentech: Employment. Masaquel:Genentech: Employment; Roche: Equity Ownership. Seetasith:Genentech: Employment, Equity Ownership.

Anticoagulation after venous thromboembolism

2013 ◽  
Vol 33 (03) ◽  
pp. 211-217 ◽  
Author(s):  
S. Eichinger
Keyword(s):  
Venous Thromboembolism ◽  
Prediction Models ◽  
Oral Anticoagulants ◽  
Bleeding Risk ◽  
Patient Characteristics ◽  
Recurrence Risk ◽  
Recurrence Rates ◽  
Clinical Patient ◽  
Recurrent Venous Thromboembolism

SummaryDeciding on the optimal duration of anticoagulation is based on the risk of recurrent venous thromboembolism (VTE) and of bleeding during anticoagulation. The duration of anticoagulation should be at least three months since shorter courses double the recurrence rates.At three months anticoagulation can be stopped in patients with a VTE provoked by a transient risk factor, as the recurrence risk is expected to be lower than the bleeding risk during anticoagulation. Patients with unprovoked VTE are at higher risk of recurrence and prolonged anticoagulation is currently recommended.However, attempts are made to stratify these patients according to their recurrence risk and to identify those with a low recurrence risk who would not benefit from extended anticoagulation. Novel approaches to optimize the management of patients with unprovoked VTE are the use of prediction models which link clinical patient characteristics with laboratory testing to discriminate between patients with a low risk (who may discontinue anticoagulation) and those with high risk (in whom long term anticoagulation is justified). Moreover, new antithrombotic concepts including new oral anticoagulants or aspirin both of which potentially confer a lower bleeding risk and are more convenient for the patients have been explored for extended thromboprophylaxis.

Durable Responses with the JAK1/ JAK2 Inhibitor, INCB018424, In Patients with Polycythemia Vera (PV) and Essential Thrombocythemia (ET) Refractory or Intolerant to Hydroxyurea (HU)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 313-313 ◽  
Author(s):  
Srdan Verstovsek ◽  
Francesco Passamonti ◽  
Alessandro Rambaldi ◽  
Giovanni Barosi ◽  
Peter J. Rosen ◽  
...  
Keyword(s):  
Median Duration ◽  
The United States ◽  
Study Medication ◽  
Employment Equity ◽  
Allele Burden ◽  
Platelet Counts ◽  
Upper Limit ◽  
Equity Ownership ◽  
Grade 3

Abstract Abstract 313 Background: While advanced PV and ET patients at high thrombotic risk are managed primarily with HU, patients who are intolerant or refractory to HU have limited therapeutic options. Identification of a dominant gain-of-function mutation in the JAK2 kinase, V617F, in myeloproliferative neoplasms (MPNs), including PV and ET, provided a key rationale for the development of a molecularly targeted therapy for these diseases. Long term follow-up data from an ongoing trial of INCB018424, a selective JAK 1/ JAK 2 inhibitor, in PV and ET patients refractory or intolerant to HU are presented. Methods: Study 18424-256 is an uncontrolled open-label Phase 2 study being conducted at 6 sites in the United States and Italy. An initial 8-week run-in evaluation established 10-mg and 25-mg twice daily as starting doses for expansion cohorts in PV and ET, respectively; dose adjustments for safety and efficacy are allowed so that each subject is titrated to their most appropriate dose. For PV, response is defined based on Hct control in the absence of phlebotomy, improvement or elimination of palpable splenomegaly when present, and normalization of leukocytosis and thrombocytosis. For ET, response is defined based on improvement or normalization of WBC and platelet counts and, when present, elimination of palpable splenomegaly. PV results (n=34; median 108 months from diagnosis): After a median follow-up of 15 months (range 8–21), 97% of enrolled subjects achieved Hct control to <45% in the absence of phlebotomy, and all continued to maintain phlebotomy-independence at the time of last follow-up visit. Splenomegaly was present in 74% of subjects at entry: 59% of those achieved ≥ 50% reduction in palpable spleen length, or the spleen became non-palpable with all maintaining spleen response at the time of the last follow-up visit. Leukocytosis > 15×109/L was present in 47% of subjects and improved (≤ 15×109/L) or normalized (≤ upper limit of normal) in 88% and 63%, respectively. Thrombocytosis > 600×109/L was present in 38% of subjects and improved (≤ 600×109/L) or normalized (≤ upper limit of normal) in 92% and 69%, respectively. 59% of subjects achieved phlebotomy independence, resolution of splenomegaly and normalization of leukocytosis and thrombocytosis. 6 patients discontinued therapy (3 due to AEs, 2 withdrew consent, 1 for no response). Grade 3 AEs potentially related to study medication included thrombocytopenia (2 patients), neutropenia (1), renal tumor (1), asthenia (1), viral infection (1), and atrial flutter (1). No Grade 4 drug-related AEs have occurred. ET results (n=39; median 84 months from diagnosis): After a median follow-up of 15 months (range 4–21), 49% of enrolled subjects normalized platelet counts to ≤ upper limit of normal after a median of 0.5 months and for a median duration of 3.5 months. 82% maintained platelet counts < 600×109/L, for a median duration of 9.8 months. Of 14 patients with baseline platelet counts > 1000×109/L, 13 have experienced > 50% reduction. 88% maintained normal WBC (median duration 14.5 months). Palpable spleens resolved in 3 of 4 subjects; 1 reduced >50% from baseline. 49% of subjects achieved normalization of WBC and platelet counts in the presence of non-palpable splenomegaly. 9 patients discontinued therapy (4 due to AEs, 2 withdrew consent, 3 for no response). Grade 3 AEs potentially related to study medication included leukopenia (2 patients), GI disorder (1), and peripheral neuropathy (1). No Grade 4 drug-related AEs have occurred. Both patient groups demonstrated reductions in patient-reported symptom scores for pruritus, night sweats, and bone pain. Of 26 PV patients reporting pruritus at baseline (median score of 6 on a 10-point scale), 24 reported scores of 0 after a median duration of 1 month and for a median duration of 7 months. 42% of PV and 56% of ET patients had at least a 20% decrease in JAK2V617F allele burden; 6% of PV and 12% of ET had >50% decrease. Clinical responses were unrelated to the presence/absence of JAK2V617F mutation at entry or to the allele burden changes following treatment. Conclusions: Rapid and durable clinical benefits (normalization of hematological parameters, resolution of splenomegaly and alleviation of symptoms) have been demonstrated in advanced PV and ET patients with >1 year of follow-up. In this study, INCB018424 continues to be a well tolerated, effective therapy in patients with PV and ET refractory or intolerant to hydroxyurea. Disclosures: Verstovsek: Incyte Corporation: Research Funding. Levy:Incyte Corporation: Employment, Equity Ownership. Bradley:Incyte Corporation: Employment. Garrett:Incyte Corporation: Employment. Vaddi:Incyte corporation: Employment. Huber:Incyte Corporation: Employment, Equity Ownership. Schacter:Pfizer Corporation: Employment. Vannucchi:Novartis: Membership on an entity's Board of Directors or advisory committees.

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