scholarly journals Association between the Leukemia Mortality-to-Incidence Ratio and State Geographic Healthcare Disparities in the United States

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3066-3066
Author(s):  
Mina Abdelmalek ◽  
Yu-Che Lee ◽  
Mazen Jizzini ◽  
Ko-Yun Chang ◽  
Yi Lee ◽  
...  
Keyword(s):  
United States ◽  
Board Of Directors ◽  
Incidence Rate ◽  
Clinical Care ◽  
The United States ◽  
Advisory Board ◽  
State Health ◽  
Advisory Committees ◽  
Potential Association ◽  
The Us

Abstract INTRODUCTION : Leukemia is the seventh leading cause of cancer death in the United States (US) in 2021. The Mortality Incidence Rate Ratio, also known as Mortality-to-Incidence Ratio (MIR), is calculated by dividing the mortality rate by the incidence rate for selected cancers and population. The MIR provides a population-based indicator of cancer survival which has previously been used to assess healthcare disparities among different countries. Here weevaluated the potential association between leukemia MIR and state-based health disparities in the US. METHODS: Leukemia (AML, CML, ALL, CLL and other leukemias) MIRs for 2008-2017 were obtained from United States Cancer Statistics (USCS) database provided by the Centers for Disease Control and Prevention (CDC). America's Health Rankings (AHR), a partnership of the United Health Foundation and the American Public Health Association, evaluates the nation's health on a state-by-state basis by using weighted measures in 5 different categories (25% for Behaviors, 22.5% for Community & Environment, 12.5% for Policy, 15% for Clinical Care, and 25% for Outcomes). AHR then determines state health rankings and reflects state health disparities based on these specific factors. Here we analyzed the potential association between leukemia MIRs and state health rankings by linear regression. RESULTS: From 2008 to 2017, a total of 489,037 people were diagnosed with leukemia and 231,069 people died from leukemia in the US. The 10-year average of age-adjusted incidence rate and mortality rate were 14.2 and 6.7 per 100,000 population respectively. The average MIR between all states was calculated to be 0.470. As seen in Table 1, the lowest MIR (best survival) was found in Florida (0.374), New York (0.391), and New Jersey (0.412) with AHR 34, 19 and 11 respectively. The highest MIR (worst survival) was found in Mississippi (0.579), Wyoming (0.570), and Ohio (0.569) with AHR 50, 24 and 37 respectively. According to AHR, over the last decade, the states with the highest health rankings were reported in Vermont (No. 1), Hawaii (No. 2), and Massachusetts (No. 3) with MIR 0.508, 0.439 and 0.502 respectively. The states with the lowest health rankings were reported in Arkansas (No. 48), Louisiana (No. 49), and Mississippi (No. 50) with MIR 0.559, 0.503 and 0.579 respectively. In our analysis, states with better health rankings were significantly associated with lower MIRs (R 2=0.232, P<0.001), as seen in Figure 1. CONCLUSIONS: There is a remarkable geographic difference in leukemia MIRs in the US between 2008-2017. Leukemia MIR was significantly associated with state health rankings reported by the AHR. Although the quality of clinical care for leukemia patients remains to be an important predictor of mortality, our findings suggest that other aggregate determinants of health, including social, economic, and community and physical environment may also play a vital role in influencing leukemia survival. More in-depth analysis of these data focusing on specific leukemia subtypes as well as other factors (race, gender, age) may be helpful in identifying and addressing other non-medical issues negativity impacting on leukemia outcomes in different geographical regions in the United States. Figure 1 Figure 1. Disclosures Wang: Kura Oncology: Consultancy, Honoraria, Other: Advisory board, steering committee, Speakers Bureau; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees; Stemline Therapeutics: Consultancy, Honoraria, Other: Advisory board, Speakers Bureau; Kite Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; Takeda: Consultancy, Honoraria, Other: Advisory board; Pfizer: Consultancy, Honoraria, Other: Advisory Board, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Advisory Board; Mana Therapeutics: Consultancy, Honoraria; BMS/Celgene: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Consultancy, Honoraria, Other: Advisory Board; Jazz Pharmaceuticals: Consultancy, Honoraria, Other: Advisory Board; DAVA Oncology: Consultancy, Speakers Bureau; Rafael Pharmaceuticals: Other: Data safety monitoring committee; Gilead: Consultancy, Honoraria, Other: Advisory board; Daiichi Sankyo: Consultancy, Honoraria, Other: Advisory board; PTC Therapeutics: Consultancy, Honoraria, Other: Advisory board; Genentech: Consultancy; MacroGenics: Consultancy.

Quality of Life after Diagnosis in Survivors of Aggressive Lymphomas

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-16
Author(s):  
Robert M. Kraft ◽  
Melissa C. Larson ◽  
Kathleen J. Yost ◽  
Thomas M. Habermann ◽  
Matthew J. Maurer ◽  
...  
Keyword(s):  
United States ◽  
General Population ◽  
B Cell ◽  
Board Of Directors ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Advisory Committees ◽  
Aggressive Lymphomas ◽  
The Us

Background: Aggressive lymphomas are potentially curable; however, long-term effects of treatment and the disease may adversely affect patients' quality of life (QoL). We investigated QoL at baseline, and up to nine years after diagnosis in survivors of aggressive lymphomas. Methods: Patients newly diagnosed with lymphoma were prospectively enrolled within nine months of diagnosis in the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma Specialized Program of Research Excellence (SPORE) and systematically followed. Patients were enrolled from September 1, 2002 until June 30, 2015. Eligibility criteria included being a United States resident, English-speaking, no history of HIV, and aged 18 years and older. All pathology was reviewed by a lymphoma hematopathologist. Aggressive lymphoma subtypes included in this analysis were diffuse large B-cell lymphoma (DLBCL), Follicular lymphoma grade III, Hodgkin lymphoma, T-cell lymphoma, other non-Hodgkin lymphoma not otherwise specified (NOS), other B-cell lymphoma NOS, and composite lymphomas. We assessed QoL using the Functional Assessment of Cancer Therapy-General (FACT-G) scale at baseline enrollment, and 1, 2, 3, 6, and 9 years post-diagnosis. FACT-G measures well-being (WB) in four domains-physical (PWB), social/family (SFWB), emotional (EWB), and functional (FWB), which are added to create a total (TOT) score. Those who completed <80% of FACT-G questions at any given time point were excluded. "Survivor" was defined as alive at 1, 2, 3, 6, and 9 year follow-up with no active disease or treatment within six months of a given time point. Because patients could be enrolled at any time within the first 9 months from diagnosis, the timing of initial QoL assessment was variable with respect to the start of lymphoma treatment. We estimated longitudinal change in QoL using mixed models incorporating scores from all available time points. The minimally important difference (MID) of 5 points for TOT and 2 points for each of the domains was used to determine clinical significance. Scores were compared to United States (US) general population normative data. All statistical analyses were performed using SAS (v 9.4). Results: From September 1, 2002 to June 30, 2015, 3,028 patients with aggressive lymphomas were prospectively enrolled in the MER, of which 2,018 completed the FACT-G baseline assessment (47% prior to therapy initiation). Of these patients, 1,144 at 1 year, 1,002 at 2 years, 943 at 3 years, 562 at 6 years, and 289 at 9 years post-diagnosis completed the FACT-G at both baseline and each of the respective time points after diagnosis, and met the definition of survivor. The median age at diagnosis of patients analyzed was 59 years (range 18-93). The cohort included 844 female patients (42%). DLBCL comprised 44% of cases, Hodgkin lymphoma 19%, T-cell lymphoma 11%, composite lymphomas 8%, other B-cell NOS 6%, other non-Hodgkin lymphoma NOS 7%, and Follicular lymphoma grade III 5%. QoL increased from baseline enrollment; the largest increase was seen from baseline to 1 year after diagnosis with a statistically and clinically significant mean TOT score difference of 6.7 points. This mean increase in TOT scores sustained over time with an increase of 7.8 points above baseline at 9 years after diagnosis. At baseline, PWB, EWB, and FWB scores were significantly lower in patients with aggressive lymphomas compared to the US general population, and SFWB scores were significantly higher (all p <0.01); however, only SFWB and EWB score differences were clinically significant as defined by MID. SFWB showed only a mild decline from baseline over the course of 9 years. Despite this, all SFWB scores were statistically and clinically significantly higher than the US general population at 1, 2, 3, 6, and 9 years after diagnosis (all p <0.01 and MID >2). Patients with aggressive lymphomas TOT scores at baseline did not differ from the US general population, while TOT scores at 1, 2, 3, 6, and 9 years post-diagnosis were statistically and clinically significantly higher. Overall, the results in the pre-treatment QoL subset were consistent with the cohort as a whole. Conclusions: In survivors of aggressive lymphomas, QoL improved primarily in the first year after diagnosis, and sustained over the course of nine years. QoL in survivors of aggressive lymphomas is higher than the United States general population at 1, 2, 3, 6, and 9 years after diagnosis. Figure Disclosures Maurer: Pfizer: Membership on an entity's Board of Directors or advisory committees; Nanostring: Research Funding; Morphosys: Membership on an entity's Board of Directors or advisory committees; Celgene / BMS: Research Funding; Kite: Membership on an entity's Board of Directors or advisory committees. Farooq:Kite, a Gilead Company: Honoraria. Cerhan:BMS/Celgene: Research Funding; NanoString: Research Funding.

Registry Of Patients Treated With Protein C Concentrate (Human) In The United States and Europe: Interim Results

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1146-1146
Author(s):  
Marilyn J. Manco-Johnson ◽  
Paul Knoebl ◽  
Amy D. Shapiro ◽  
Maureen Finnerty ◽  
Leman Yel ◽  
...  
Keyword(s):  
United States ◽  
Board Of Directors ◽  
Research Funding ◽  
Protein C ◽  
The United States ◽  
Employment Equity ◽  
Advisory Committees ◽  
Protein C Concentrate ◽  
Concentrate Treatment ◽  
Equity Ownership

Abstract Background Protein C (PC) is a naturally occurring, vitamin-K dependent anticoagulant produced by the liver. Deficiency of PC, which can be congenital or acquired, results in a hypercoagulable state. Patients with severe PC deficiency may manifest severe, often life-threatening, disseminated intravascular coagulation (DIC), purpura fulminans (PF), and/or thromboembolism. Highly purified protein C concentrate prepared from human donor plasma (Ceprotin; Baxter Healthcare Corporation, Westlake Village, CA) is an approved therapy for prevention and treatment of venous thrombosis and PF in patients with severe congenital PC deficiency (SCPCD) in the United States. It is indicated in patients with SCPCD for PF and coumarin-induced skin necrosis, and short-term prophylaxis in the European Union and other countries. Use of protein C concentrate (human) has been reported in patients with acquired PC deficiency. The Ceprotin Treatment Registry is a prospective, international, multi-center, open-label, non-interventional, observational study designed to examine the long-term safety and effectiveness of protein C concentrate (human) in the clinical setting. This is the first large, real-world assessment of the treatment of a rare disease with protein C concentrate (human). Here we report data from the first interim analysis in June 2013 covering a 3-year enrollment period. Methods Patients of any age who received, or were initiating/receiving protein C concentrate are included. The study duration is 5 years (3-year enrollment period plus 2 years of follow-up). All study visits/assessments are in accordance with standard of care, with protein C concentrate dose, dose frequency, duration and route of administration determined by the investigator. The study objectives are to determine the most common medical diagnoses associated with protein C concentrate treatment, protein C concentrate treatment regimens, and safety information based on all serious adverse events (SAEs) and rate of treatment-related AE. Other objectives include: an examination of the relationship between protein C concentrate treatment and outcomes in all registry participants, as well as various subgroups. Descriptive statistical analyses are used. Results At the time of data extraction, 34 patients were enrolled from 26 centers; 10 centers in the United States and 16 centers in Europe. Half of the patients were males. The primary diagnosis of PC deficiency was congenital in 25 patients (73.5%) and acquired in 9 patients (26.5%). The median age at diagnosis was 0.03 years (range 0–19.9). Mean plasma PC activity level was 9% (range 1–40.0). The most common (in ≥3 patients) thrombotic disease-associated conditions were PF (50.0%); blindness (44.1%); thromboembolic disease (41.2%), which included deep vein thrombosis, arterial thrombosis and DIC; stroke (32.4%), and renal dysfunction (8.8%). Of the 23 patients being treated with protein C concentrate, 15 were administered protein C concentrate intravenously, and 8 patients received protein C concentrate subcutaneously. The body weights of patients receiving subcutaneous treatment ranged from 10.0 kg to 57.9 kg. A total of 15 patients received an anticoagulant treatment in addition to protein C concentrate. Eight patients reported 23 SAEs, all of which were considered not related to treatment. Eighteen (52.9%) patients reported 72 AEs; only 1 of them, an episode of upper respiratory infection, was considered possibly treatment-related. In 18 patients in whom PC activity recovery was determined after protein C concentrate treatment, there were no patients documented with poor recovery. Protein C concentrate was used during 18 surgeries/invasive procedures and considered effective in all interventions for which data were available. Conclusions Data from the first interim analysis of the Ceprotin Treatment Registry demonstrate that patients with both congenital and acquired severe PC deficiency who are treated with protein C concentrate (human) have a low incidence of treatment related SAEs and AEs, and treatment with protein C concentrate appears to be effective when used during surgery/invasive procedures. Further patient follow up will shed light onto clinical treatment outcomes. Disclosures: Manco-Johnson: CSL Behring: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Novo Nordisk: Membership on an entity’s Board of Directors or advisory committees; Biogen Idec: Membership on an entity’s Board of Directors or advisory committees; Baxter BioScience: Membership on an entity’s Board of Directors or advisory committees; Bayer HealthCare: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Eisai: Research Funding. Knoebl:Novo Nordisk: Consultancy, Honoraria; Baxter: Consultancy, Honoraria. Shapiro:Cangene: Research Funding; Biogen Idec: Research Funding; Baxter BioScience: Research Funding; Bayer HealthCare: Research Funding. Finnerty:Baxter: Employment, Equity Ownership. Yel:Baxter: Employment, Equity Ownership. Gelmont:Baxter: Employment, Equity Ownership.

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

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

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

scholarly journals Real-World Evidence on Treatment Utilization in Lower-Risk Myelodysplastic Syndromes: Findings from a Medical Record Review in the United States

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4666-4666
Author(s):  
Ulrich Germing ◽  
Ravi K. Goyal ◽  
Aylin Yucel ◽  
Rohan C. Parikh ◽  
Maria Jimenez ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Lower Risk ◽  
Research Funding ◽  
The United States ◽  
Full Time ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Advisory Committees ◽  
The Us

Abstract Introduction: Patients diagnosed with myelodysplastic syndromes (MDS) are at an increased risk for developing infections, bleeding events, cardiopulmonary complications, and progressing to acute myeloid leukemia (AML). Patients with lower-risk MDS experience a mean life-year loss of about 6 years, and the main focus of treatment is on management of cytopenias, in particular anemia. Currently, limited real-world evidence exists on prevailing treatment patterns and outcomes in lower-risk MDS in the United States (US). Methods: In this retrospective, non-interventional review of medical records, eligible patients (≥ 18 years of age) with diagnosis of lower-risk MDS (with or without ring sideroblasts and with single-lineage or multilineage dysplasia) between July 1, 2013 and September 30, 2018, were identified by participating clinicians. Patients with prior history of AML or other malignant neoplasms were excluded. This is an ongoing study in the US and interim data are described. Study measures descriptively summarized patient demographics, clinical characteristics at MDS diagnosis, and utilization of medication treatments for the management of anemia. Results: Data from medical records of 50 patients with lower-risk MDS were abstracted by 26 hematologist-oncologists in the US. Participating clinicians had been managing treatment for hematology/oncology patients for an average (standard deviation [SD]) of 16.3 (6.7) years, 53.9% practiced in an academic hospital or cancer center, and 46.2% practiced in a community setting. The mean (SD) age for patients with lower-risk MDS at diagnosis was 64.2 (9.9) years, 64.0% were male, 70.0% were White, and 60% were insured primarily through Medicare. Most patients (54.0%) had Low-risk MDS (as categorized by Revised International Prognostic Scoring System) followed by Very low-risk (28.0%), and Intermediate-risk (18.0%) at initial diagnosis. The most common gene mutations observed were JAK2 (22.0%) and ASXL1 (8.0%). The most common karyotype abnormalities observed were del(5q) (28.0%), −Y (14.0%), and del(7q) (12.0%). During the 12 months before diagnosis of lower-risk MDS, cardiac complications were observed among 18.0% of patients, and 58.0% of patients were either current or former smokers at the time of diagnosis of lower-risk MDS. At the time of data abstraction, mean (SD) follow-up time was 39.6 (21.6) months, and 46 (92.0%) patients had received ≥ 1 line of treatment for MDS-associated anemia. Of these 46 patients, 93.5% received first-line treatment with an erythropoietin-stimulating agent (ESA). In the first-line, most patients received ESA monotherapy (n = 37; 80.4%) followed by ESA-based combination therapy (n = 6; 13.0%), lenalidomide only (n = 2; 4.4%), and azacitidine (n = 1; 2.2%). All 18 patients who received a second-line treatment had received an ESA-based first-line treatment. Second-line treatments received were ESA-based treatment (n = 5; 27.8%), lenalidomide only (n = 5; 27.8%), luspatercept only (n = 4; 22.2%), azacitidine only (n = 3; 16.7%), and filgrastim only (n = 1; 5.6%). Third-line treatment was only observed in 3 patients. Conclusions: In this ongoing study, current analysis for 50 patients with lower-risk MDS in the US showed ESA-based regimens were the most common first-line therapy. ESA-based treatment was again utilized as second-line therapy among some patients who were previously treated with ESA. Disclosures Germing: Janssen: Honoraria; Celgene: Honoraria; Novartis: Honoraria, Research Funding; Jazz Pharmaceuticals: Honoraria; Bristol-Myers Squibb: Honoraria, Other: advisory activity, Research Funding. Goyal: RTI Health Solutions: Other: Full-time employee of RTI Health Solutions, which is business unit of RTI International, a non-profit research organization, which received funding from BMS to conduct this study.. Yucel: BMS: Current Employment, Current holder of individual stocks in a privately-held company. Parikh: RTI-Health Solutions: Other: Full-time employee of RTI-HS, which received funding to conduct this study from BMS.. Jimenez: RTI Health Solutions: Current Employment. Sluga-O'Callaghan: RTI Health Solutions: Current Employment. Tang: Bristol-Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Hughes: BMS: Current Employment. Diez-Campelo: Takeda Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

Treatment Patterns from 2009 to 2015 in Patients with Newly Diagnosed Multiple Myeloma in the United States: A Report from the Connect® MM Registry

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4489-4489 ◽  
Author(s):  
Robert M. Rifkin ◽  
Rafat Abonour ◽  
Brian G.M. Durie ◽  
Cristina J. Gasparetto ◽  
Sundar Jagannath ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
The United States ◽  
Treatment Patterns ◽  
Second Line ◽  
Newly Diagnosed ◽  
First Line ◽  
Advisory Committees ◽  
Frequency Of Use ◽  
The Us

Abstract Introduction: Between 2009 and 2015, use of novel therapies (immunomodulating drugs and proteasome inhibitors) in multiple myeloma (MM) increased. Regimens initiated during this time frame may help project near-term future treatment patterns. Connect® MM is the first and largest prospective, observational, US-based, multicenter disease registry designed to characterize treatment patterns and outcomes for patients (pts) with newly diagnosed MM (NDMM). Pts with NDMM were enrolled in 2 sequential cohorts from Sep 2009 to Apr 2016. This noninterventional registry did not prescribe or limit therapy choices. Study sites represented all census regions, with 89% and 11% split between community and academic sites, respectively. This allowed a reasonable generalizability to patterns for the US. Methods: Connect® MM enrollment was initiated in Sep 2009 at 250 community and academic sites. Pts were enrolled within 2 months of diagnosis. Cohort 1 enrolled 1493 NDMM pts from Sep 2009 to Dec 2011, and Cohort 2 enrolled 1518 NDMM pts from Dec 2012 to Apr 2016. Data were collected at a baseline visit and quarterly visits thereafter until death or discontinuation. The current analysis was conducted for the population of treated pts (N=2848) as of May 2016. This study examined recorded treatment choice of first-line regimen, maintenance therapy, and second-line regimen in 6-month intervals. Trends in regimens were graphically represented using "Tepee" plots (Srinivasan, Shankar. Resource Tepee. Patent US 7,495,673 B1. 24 Feb 2009). Briefly, all pts who initiated treatment during each 6-month interval are represented horizontally, with each horizontal line indicating 100% of all treatment used in that period. The regimens are represented by gray shading with wider bands signifying the more frequently used regimens at each time interval. Results: Median follow‐up for all pts was 39.3 months (0.03‐78.4) in Cohort 1 and 15.4 months (0.2-40.1) in Cohort 2. For the treated population, the median age was 67 years (range 24‐94), 58% were male, 83% were white, and 38% of those reporting International Staging System stage had stage III MM. By US geographical region, 329 (11.6%) pts were from the Northeast, 1036 (36.4%) from the Midwest, 1117 (39.2%) from the South, 360 (12.6%) from the West, 4 (0.1%) from Puerto Rico, and 2 missing (0.05%). Most pts (2285; 80.2%) were from community sites, and 397 (13.9%) were from academic sites with the remaining from government sites. A total of 1416 (47.4%) reported an intent to transplant (stem cell transplant [SCT]) at the initiation of therapy. A total of 666 (25.8%) have progressed and entered second line. Tepee plots of treatment patterns for start of induction for those pts with and without SCT intent are provided in Figure 1A and 1B, respectively. The year 2012 does not feature in these induction plots, as this period corresponds to a time when pts were not enrolled-Cohort 1 had been completed and Cohort 2 had not yet opened. The 4 most common induction regimens for SCT intent, from left to right, in order of decreasing frequency of use, were lenalidomide (R), bortezomib (V), dexamethasone (D) combined (RVD); VD; cyclophosphamide plus VD (CyBorD); and RD. The 5 most common induction regimens for those without SCT intent, from left to right, in order of decreasing frequency of use, were VD, RD, RVD, CyBorD, and V. Triplet therapy in first-line induction pts increased in frequency from 2009 to 2014. The 4 most frequent maintenance regimens for those with SCT intent were R monotherapy, V monotherapy, RD, and RVD. The 4 most common maintenance regimens for pts who did not intend to receive SCT were R monotherapy, RD, VD, and V monotherapy. The most prevalent regimens in the second line were VD, RD, V, and RVD. Additional graphs including treatment patterns by age group (≤ 70 vs > 70 years) and maintenance by conduct of first-line SCT will be presented. Conclusions: Our work utilizes Tepee plots to outline induction and maintenance treatment patterns over time, for both SCT and non-SCT intent pts, using the largest, prospective, noninterventional registry study in the US. Triplet therapy use increased in the time period studied, with RVD being the most frequently used triplet for pts with or without SCT intent. The most common maintenance regimens included R as monotherapy or in combination. Disclosures Rifkin: Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Amgen/ONYX: Membership on an entity's Board of Directors or advisory committees. Abonour:Celgene: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen: Consultancy; Janssen: Consultancy; Takeda: Consultancy. Gasparetto:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria. Jagannath:Bristol-Myers Squibb: Consultancy; Celgene: Consultancy; Merck: Consultancy. Terebelo:Celgene: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene: Consultancy. Kitali:Celgene: Employment, Equity Ownership. Zafar:Celgene: Employment. Srinivasan:Celgene: Employment; Individual Patent: Patents & Royalties: US7,495,673B1 Used for MM-Connect Treatment Patterns Abstract.. Hardin:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees.

scholarly journals No Difference in Survival Among Black Patients with Mycosis Fungoides and Sézary Syndrome: A Multicenter Retrospective Analysis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2441-2441
Author(s):  
Pamela Allen ◽  
Subir Goyal ◽  
Irl Brian Greenwell ◽  
Jane Scribner ◽  
Sunil Rangarajan ◽  
...  
Keyword(s):  
United States ◽  
Board Of Directors ◽  
Mycosis Fungoides ◽  
Median Survival ◽  
Systemic Therapy ◽  
Research Funding ◽  
The United States ◽  
Insurance Status ◽  
Stage At Diagnosis ◽  
Advisory Committees

Abstract Introduction Black (B) patients with Mycosis fungoides and Sézary Syndrome (MF/SS) have inferior survival and distinct clinical presentations, including many high risk features compared to non-black (NB) patients with MF/SS in large registry studies from the United States. We sought to characterize clinical differences in presentation, treatment, and outcomes to identify drivers of disparities among B patients with MF/SS. Methods We performed a retrospective review of 417 patients with MF/SS diagnosed between 1990 and 2020 at 6 academic institutions in the United States that serve populations with large numbers of Blacks and minorities. Patients with pathologic review and a confirmed histopathologic diagnosis of MF or SS with a stage &gt;1B as their highest TNMB stage were eligible for inclusion. The primary objective was to assess differences in clinical characteristics, treatment patterns, and survival between B and NB patients. Clinical variables included demographics, insurance, zip code, tumor characteristics, and treatment. Descriptive analysis was performed for each variable. Comparison between B and NB patients utilized ANOVA for numerical covariates and chi-square test or Fisher's exact test for categorical covariates. Kaplan-Meier curves for OS were generated, and subgroups were analyzed separated. Results Among 417 patients, 204 (48.9%) were Blacks, 196 (47.0%) were White, and (4.1%) were other races (8 Asian, 5 unknown, 4 Hispanic). The diagnosis was MF in 366 (87.8%), SS in 47 (11.3%), and other 4 patients. Stage at diagnosis was available for 384 patients. 37 (9.6%) were stage 1A, 165 (43%) were stage 1B, 34 (8.9%) were stage 2A, 58 (15.1%) were stage 2B, 44 (11.5%) were stage 3, and 46 (12%) were stage 4 at diagnosis. The median survival of the whole cohort (n=417) was B patients were younger (median 50.1 years in B vs. 60.5 in NB, p&lt;0.001), more often female (49.5% in B; 35.7% in NB, p=0.004), had higher rates of reported lymphadenopathy (78.5% vs. 70%, p=0.039), longer delays from symptom onset to diagnosis (2.0 years in Black vs. 1.2 years in NB, p=0.014), and higher rates of bacteremia at any time in their disease course (19.7% in Black, vs. 6.6% in NB, P&lt; 0.001) compared to NB patients. There was no difference in insurance status (private, Medicare/Medicaid, or uninsured) or comorbidities by race. There was also no differences in overall TNMB stage at diagnosis (p=0.14) compartment stage, or highest stage (p=0.076). Progression to a higher T, N, M, or B stage occurred at similar frequencies in B and NB patients (n=83 (43.2%) in Black and n=73 (38.8%) in NB, p=0.38). Time to first therapy, time to systemic therapy, or total lines of therapy also did not differ by racial group. A greater fraction of B compared to NB patients received systemic therapy but this did not reach statistical significance (72.6% in Black vs. 62% in NB, p=0.060). There was no difference in large cell transformation at any point, or white blood cell count (WBC), lactate dehydrogenase (LDH), or T-cell receptor (TCR) clonality in skin/blood at diagnosis. On univariate analysis, race was not associated with survival; the median survival was 10.5 years (95% CI 8-13.2) in B patients and 10.9 years (95% CI 7.2-14.1) in NB patients. Covariates associated with inferior survival included older age (p&lt;0.001), number of comorbidities (p&lt; 0.001), bacteremia (p&lt; 0.001), higher overall TNMB stage, higher individual T, N, M and B stage, progression to a higher N or M stage, positive TCR in the blood, WBC value, and LDH value. Insurance status and year of diagnosis (prior to 2010, vs. following 2010) were not associated with survival. On multivariate cox proportional hazard model, age at diagnosis, comorbidities, extra-cutaneous disease, bacteremia, TNMB stage at diagnosis, and progression to a higher nodal stage remained statistically significant for survival. Conclusions We present the first multicenter analysis of racial disparities in MF/SS, with nearly 50% B patients. B patients had distinct presentations, delay in diagnosis, and higher rates of bacteremia compared to NB patients. In contrast to US-registry studies, there was no difference in survival between B and NB patients. This finding could be explained by access to academic centers and/or higher rates of insurance coverage among B patients in our cohort. Additional analyses will be updated at the time of the presentation. Figure 1 Figure 1. Disclosures Allen: ADC Therapeutics: Consultancy; Kyowa Kirin: Consultancy; Secure Bio: Consultancy. Mehta: Seattle Genetics; Incyte; TG Therapeutics: Consultancy; Seattle Genetics; Incyte; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Affirmed; Kite/Gilead; Roche-Genetech; Celgene/BMS; Oncotartis; Innate Pharmaceuticals; Seattle Genetics; Incyte; Takeda; Fortyseven Inc/Gilead; TG Therapeutics; Merck; Juno Pharmaceuticals/Bristol Myers Squibb: Research Funding. Huen: Rhizen: Research Funding; Elorac: Research Funding; Kyowa Kirin: Research Funding; Tillium: Research Funding; Innate: Research Funding; Galderma: Research Funding; Miragen: Research Funding. Porcu: Viracta: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Innate Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BeiGene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Incyte: Research Funding; Daiichi: Honoraria, Research Funding; Kiowa: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Spectrum: Consultancy; DrenBio: Consultancy.

scholarly journals Defibrotide for the Treatment of Hepatic Veno-Occlusive Disease: An Update from the International Compassionate Use Program in 710 Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1138-1138 ◽  
Author(s):  
Selim Corbacioglu ◽  
Enric Carreras ◽  
Mohamad Mohty ◽  
Antonio Pagliuca ◽  
Maria Ballabio ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Dose Group ◽  
The United States ◽  
Outcome Data ◽  
Occlusive Disease ◽  
Compassionate Use ◽  
Advisory Committees ◽  
The Us ◽  
Daily Dose

Abstract Introduction: Hepatic veno-occlusive disease (VOD; also called sinusoidal obstruction syndrome) is a potentially fatal complication of hematopoietic stem cell transplantation (HSCT). Severe VOD (sVOD) is usually characterized by multi-organ failure (MOF) and >80% mortality. sVOD may develop in a substantial number of high risk patients (pts) and is often unpredictable. Defibrotide is an oligonucleotide that protects endothelial cells from transplant-induced damage and restores the thrombotic-fibrinolytic balance. Defibrotide is now approved in the EU for the treatment of severe hepatic VOD in HSCT. We report here the final results of a large, international compassionate use program (CUP), open from 1998-2009. Methods: Defibrotide was provided on a compassionate basis or via single pt emergency-use requests (collectively, the CUP) to 312 sites in Europe, the US, Asia and the Middle East. There was no protocol; however, eligibility data, defibrotide use, safety and outcome data were requested using case record forms. In the US, pts were required to meet Baltimore criteria for VOD and have MOF. At all other sites, pts who met Seattle criteria for VOD, ultrasound, or histological criteria were eligible. The program included pts diagnosed with VOD as a complication of HSCT as well as chemo-/radiotherapy. Defibrotide was recommended to be administered IV in 4 divided doses daily, each dose infused over 2 hours. The initial dosing recommendations were 10 mg/kg/day with incremental dose increases of 10 mg/kg every 24 to 48 hours to a maximum daily dose of 60 mg/kg, depending on tolerability and response to treatment. Following results of a US Phase 2 study, the dose recommendation was 25 mg/kg/day. Duration of treatment was at the discretion of the investigator. Reported data included adverse events (AEs) and survival at Day+100 post HSCT or chemo-/radiotherapy. Results: Enrollment data were provided for 1129 pts. Safety and outcome data (submitted voluntarily) were provided for 710 pts reported to have received ≥1 dose of defibrotide (433 male [61%]). Of these, 628 (89%) developed VOD following HSCT (499 [71%] allogeneic; 112 [16%] autologous; 17 [2%] other/missing) and 79 (11%) developed VOD following chemo-/radiotherapy alone; information on the index event that led to VOD was missing for 3 pts. The median age was 25 (range, 0.2-70) years; 303 (43%) were <18 years. In the 710 pts, median time to onset of VOD from HSCT or start of chemo-/radiotherapy was 13 days. A total of 623 (88%) had bilirubin >2 mg/dL, 584 (82%) had weight gain >5%, 548 (77%) had hepatomegaly, 477 (67%) had ascites, 455 (64%) had right upper quadrant pain, and 292 (41%) had MOF. Per Bearman criteria or MOF, 429 (60%) had sVOD. The median daily dose of defibrotide was 25 mg/kg given for a median of 15 days. The most common doses were 25 or 40 mg/kg/day (498 of 638 pts with dosing information, 78%). AEs were reported in 378 pts (53%); most were serious (364/710, 51%) and fatal (350/710, 49%). Causes of death were generally reported as AEs, hence the most common new or worsening AEs were recorded as MOF (n=144 [20%], all fatal) and VOD (n=79 [11%], 78 fatal). Among the other AEs, sepsis (n=49 [7%], 48 fatal) was the most common. Incidence of serious AEs and fatalities was generally similar across dose subgroups. At least one hemorrhage event was reported by 85 (12%) pts (55 serious, including 37 fatal), most commonly gastrointestinal (n=33, 5%) or respiratory (n=24, 3%). Central nervous system (CNS) hemorrhage was reported in 10 pts (1%). Respiratory tract hemorrhage was highest in the 60/80 mg/kg/day dose group (9%) vs lower doses (<5%), but gastrointestinal and CNS hemorrhages were similar across dose groups (4%-6% and 0%-2%, respectively). Sixty three (9%) pts withdrew due to an AE, most due to hemorrhage (n=50, 7%), which was primarily gastrointestinal (n=22, 3%). Across all doses in the 710 pts evaluated, the Kaplan-Meier (KM) estimate of survival at Day+100 was 54%. Figure shows KM estimated survival by dose group; in the 25 mg/kg/day subgroup (the approved EU dose) it was 58% at Day+100. Conclusions: This large compassionate-use experience demonstrated that defibrotide was generally well tolerated and AEs were typical for this population. The overall KM estimated survival rate of 54% at Day+100 is consistent with prior studies. Results from subgroup analyses support the 25 mg/kg/day dosing as an optimal approach. Support: Jazz Pharmaceuticals Figure 1 Figure 1. Disclosures Corbacioglu: Gentium: Consultancy, Honoraria. Off Label Use: Defibrotide is an investigational treatment for veno-occlusive disease in the United States.. Carreras:Gentium S.p.A.: Expert Testimony Other, Research Funding, Speakers Bureau. Mohty:Gentium S.p.A./Jazz Pharmaceuticals Inc.: Honoraria, Research Funding. Pagliuca:Gentium S.p.A.: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Ballabio:Jazz Pharmaceuticals Inc.: Employment, Equity Ownership. Hume:Jazz Pharmaceuticals Inc.: Employment. Bandiera:Gentium S.p.A.: Employment. Finetto:Gentium S.p.A.: Employment. Richardson:Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals Inc.: Research Funding.

scholarly journals The Role of Proteasome Activator PA28α in Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5499-5499
Author(s):  
Yanyan Gu ◽  
Benjamin G Barwick ◽  
Mala Shanmugam ◽  
Craig C Hofmeister ◽  
Jonathan L. Kaufman ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Plasma Cells ◽  
Hematologic Malignancy ◽  
The United States ◽  
Myeloma Cell ◽  
Advisory Board ◽  
20S Proteasome ◽  
Advisory Committees

Multiple myeloma (MM) is a commonly occurring hematologic malignancy in the United States with poor prognosis. Among all treatments, proteasome inhibitor (PI) based regimens have been a major breakthrough for patients' outcomes. Available PIs all target 20S proteasome core complex, and the duration of response is limited by toxicity and resistance development. Until now, the underlying mechanism of drug resistance remains unclear. The proteasome is the major proteolytic machinery in protein homeostasis which is pivotal for myeloma cell survival. A functional proteasome consists of 20S proteasome core particle with regulatory particle on one or both ends. There are 3 types of proteasome regulators that could activate a 20S proteasome, PA700 (19S), 11S REG (PA28) and PA200. The 11S REG (PA28) protein family consists of three members, α, β, and γ. PA28 α/β are IFN-γ inducible and with higher expression in antigen presenting cells. Currently, the function of 11S subunit remains largely unknown. Our analysis of plasma cells from MM patients and healthy donors has demonstrated that expression of 11S proteasome is higher in myeloma cells than normal plasma cells and progressively upregulated with disease progression. To further identify the function of 11S proteasome especially PA28α in MM, we generate PA28α knockdown stable MM cell lines. We have found that knockdown of PA28α inhibits MM cell growth and proliferation, also induces myeloma cell resistance to PIs. The mechanism of PI resistance is different from knocking down of 19S or 20S proteasome subunits. Silencing of PA28α inhibits proteasome activity and decreases proteasome work load concurrently, resulting in a favorable proteasome load vs capacity ratio. Altogether, in this report, we describe the function of PA28α in MM cells, also provide novel insights into regulating PIs sensitivity through modulation of the 11S proteasome subunit PA28α. Disclosures Hofmeister: Nektar: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Imbrium: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Kaufman:Karyopharm: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria; Amgen: Consultancy; Bristol-Myers Squibb: Consultancy; Incyte: Consultancy; Celgene: Consultancy; Winship Cancer Institute of Emory University: Employment; AbbVie: Consultancy; Takeda: Consultancy; TG Therapeutics: Consultancy. Nooka:Amgen: Honoraria, Other: advisory board participation; GSK: Honoraria, Other: advisory board participation; Celgene: Honoraria, Other: advisory board participation; Takeda: Honoraria, Other: advisory board participation; Spectrum pharmaceuticals: Honoraria, Other: advisory board participation; BMS: Honoraria, Other: advisory board participation; Janssen: Honoraria, Other: advisory board participation; Adaptive technologies: Honoraria, Other: advisory board participation. Boise:Genentech Inc.: Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Research Funding. Lonial:Takeda: Consultancy, Research Funding; Amgen: Consultancy; BMS: Consultancy; Janssen: Consultancy, Research Funding; GSK: Consultancy; Karyopharm: Consultancy; Genentech: Consultancy; Celgene Corporation: Consultancy, Research Funding.

scholarly journals A Phase 1/2 Study to Evaluate the Safety and Efficacy of Ponatinib with Chemotherapy in Pediatric Patients with Philadelphia Chromosome-Positive (Ph+) Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 47-47
Author(s):  
Yousif Matloub ◽  
Lia Gore ◽  
Mignon L. Loh ◽  
Chin-Hon Pui ◽  
Michael J. Hanley ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Pediatric Patients ◽  
Phase 1 ◽  
The United States ◽  
Advisory Board ◽  
Marketing Approval ◽  
Phase 2 ◽  
Advisory Committees ◽  
Free Survival ◽  
Secondary Endpoints

Introduction: Ph+ ALL accounts for 3-5% of pediatric ALL and is associated with improved outcomes when tyrosine kinase inhibitors (TKIs) are added to chemotherapy, with 5-year event-free survival (EFS) and overall survival (OS) of 58-60% and 70-86%, respectively. Ponatinib is a potent third-generation TKI pan-BCR-ABL1 inhibitor that is active against BCR-ABL1 and all identified single resistance mutations, including the gatekeeper alteration, T315I, which confers resistance to other TKIs. Ponatinib has marketing approval in more than 50 countries, which includes the United States and European Union, for adults with chronic-/accelerated-/blast-phase chronic myeloid leukemia or Ph+ ALL that are resistant/intolerant to other TKIs or are T315I+. Ponatinib may also overcome drug resistance in pediatric patients with relapsed or resistant Ph+ ALL. This study will assess the pharmacokinetics, safety, and efficacy of ponatinib in pediatric patients. Methods: This Phase 1/2, single-arm, open-label, multicenter study (NCT04501614) will enroll approximately 18 patients in Phase 1 and 68 patients in Phase 2, including those enrolled in Phase 1 at the recommended Phase 2 dose (RP2D). Patients (aged ≥1 year to ≤21 years) with Ph+ ALL, Ph+ mixed phenotype acute leukemia, or Ph-like ALL (US only) with ABL class lesions will be enrolled. Enrolled patients must have either relapsed or are resistant or intolerant to ≥1 prior therapy with a BCR-ABL1-targeted TKI or have a BCR-ABL1 T315I mutation. Patients &gt;16 years must have a Karnofsky performance status ≥50%; patients ≤16 years must have a Lansky Play Scale ≥50%. During Phase 1, prior to availability of an age-appropriate formulation (AAF), patients must weigh ≥30 kg and be able to swallow tablets. The Phase 1 study will establish the RP2D of ponatinib in combination with the chemotherapy backbone using the adult tablet formulation in patients able to swallow tablets. Patients will receive fixed doses of ponatinib based on body weight ranges. The initially selected doses are expected to achieve systemic exposures that approximately match adult exposures after a 30-mg dose. Dose selection for the AAF will be in a separate cohort and informed by the results of a relative bioavailability study in healthy adult volunteers. A rolling 6 design will be used for both cohorts; additional cohorts may be enrolled at lower or higher doses based on the emerging data. In both Phase 1 and Phase 2, patients will receive two 35-day blocks of therapy (reinduction and consolidation). Each block includes 29 days of study treatment consisting of daily ponatinib and a modified United Kingdom ALL R3 chemotherapy backbone regimen, followed by a rest period of at least 6 days with daily ponatinib only. Disease assessment will occur at the end of each block. Patients will undergo an end-of-treatment visit 25 to 30 days after the last dose of study treatment in the consolidation block, or earlier if the patient is proceeding to alternate therapy or optional ponatinib continuation therapy. For the Phase 1 study, the primary endpoint is the RP2D of ponatinib (tablet and AAF) in combination with chemotherapy. Secondary endpoints are complete response (CR) rate at the end of the reinduction block and characterization of BCR-ABL1 domain mutations prior to and following ponatinib treatment. For the Phase 2 study, the primary endpoint is the CR rate at the end of the reinduction block. Secondary endpoints will be summarized descriptively, and include the proportion of patients in continued CR or who achieve CR at the end of consolidation, the proportion with minimal residual disease-negative status &lt;0.01% at the end of each block, and the proportion who relapsed or progressed, and time-to-event estimates including EFS, progression-free survival, and OS. The study will include approximately 70 study sites in approximately 16 countries. Disclosures Matloub: Takeda: Current Employment. Gore:Amgen, Novartis, Roche: Membership on an entity's Board of Directors or advisory committees. Loh:Medisix Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Other: Institutional Research Funding. Pui:Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees. Hanley:Takeda: Current Employment. Lu:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Current Employment. Leonard:Takeda: Current Employment. Granier:Incyte: Current Employment. Silverman:Servier: Other: advisory board; Syndax: Other: advisory board; Takeda: Other: advisory board. OffLabel Disclosure: Ponatinib has marketing approval in the United States and European Union for adult patients with chronic-/accelerated-/blast-phase chronic myeloid leukemia or Ph+ ALL that are resistant/intolerant to other TKIs or are T315I+. This trials-in-progress abstract describes a study in pediatric patients.

Results of an Early Access Treatment Protocol (EAP) of Daratumumab in United States Patients with Relapsed or Refractory Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2133-2133
Author(s):  
Ajai Chari ◽  
Tomer M Mark ◽  
Amrita Krishnan ◽  
Keith Stockerl-Goldstein ◽  
Saad Z Usmani ◽  
...  
Keyword(s):  
United States ◽  
Multiple Myeloma ◽  
Board Of Directors ◽  
Research Funding ◽  
Treatment Protocol ◽  
The United States ◽  
Advisory Committees ◽  
Early Access ◽  
Patient Reported ◽  
Grade 3

Abstract Background: Daratumumab (dara) is a human CD38-directed monoclonal antibody indicated for the treatment of patients (pts) with multiple myeloma (MM) who have received ≥3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMID) or who are double-refractory to a PI and an IMID. Accelerated approval was granted in the United States (US) in November 2015, based largely on the results of MMY2002, a pivotal phase 2 study in this pt population. Methods: The objectives of this multicenter, open-label early access treatment protocol (EAP) were to provide early access to dara treatment and collect safety and patient-reported outcome (PRO) data in this pt population. Eligibility criteria were similar to those of pivotal study MMY2002 and included age ≥18 years, documented MM, progression by IMWG criteria following the most recent therapy, ≥3 prior lines of therapy including a PI and an IMID or disease double-refractory to a PI and an IMID, ECOG performance status score 0-2, no known chronic obstructive pulmonary disease or persistent asthma, no ongoing MM therapy, and no prior exposure to anti-CD38 antibody therapy. Pts received dara 16 mg/kg IV weekly for 8 weeks, then every 2 weeks for 16 weeks, and then every 4 weeks until disease progression, unacceptable toxicity, or 60 days after US approval. Pre- and post-infusion medications were administered as in study MMY2002. Serious adverse events (SAEs), grade 3-4 AEs, infusion related reactions (IRRs), and PRO data were collected. Results: In total, 400 pts were screened and 348 pts were enrolled and dosed at 39 US sites from July to November 2015. Median age was 65 (range 27-94) years; 72% were white, and 17% were African American. Three-fourths of pts were symptomatic with an ECOG score of 1 (58%) or 2 (16%). Pts received a median of 8 (range 1-17) doses, and median treatment exposure was 1.9 (range 0.03-6.0) months. Median durations of infusion were 7.4, 4.4, and 3.5 hours for the first, second, and all subsequent infusions, respectively. Half of pts (52%) transitioned to commercial drug after marketing authorization, whereas 37% discontinued due to progressive disease. Treatment emergent grade >3 AEs were reported in 51% of pts. The most common grade ≥3 AEs were thrombocytopenia (15%) and anemia (14%). SAEs occurred in 35% of pts, including 12% of pts with SAEs which were reported by investigators as drug-related. The most common SAEs were infections, which occurred in 11% of pts. Nine percent of pts discontinued therapy due to AEs, including 3% for drug-related AEs. Thirteen (4%) pts had an AE with a fatal outcome, including 2 (0.6%) pts with drug-related AEs (pyrexia, thrombocytopenia/ subdural hematoma). IRRs occurred in 56% of pts, including 8% with grade >3 IRRs. IRRs occurred in 56%, 2%, and 2% of first, second, and all subsequent infusions, respectively; the most common IRRs were respiratory or thoracic symptoms (cough, dyspnea, throat irritation, nasal congestion), which occurred in 31% of pts. The median change from baseline in all the domains of the EQ-5D-5L and EORTC QLQ-C30 scales after 1 and 2 cycles as well as at pts' last assessment was 0, with the exception of EQ-5D-5L VAS, which showed a median increase of 1 and 2 units after 1 and 2 cycles, respectively. Conclusions: EAP results in US pts confirmed the safety profile of dara in MM pts with >3 prior therapies including a PI and IMID or who were refractory to both PI and IMID. SAEs occurred in one-third of pts, but only 12% of pts experienced a drug-related SAE. More than half of pts experienced IRRs, which primarily occurred during the first infusion and were grade 1-2 in severity. Pts maintained their health-related quality of life during a median duration of 2 months of therapy. Disclosures Chari: Array Biopharma: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Amgen Inc.: Honoraria, Research Funding; Takeda: Consultancy, Research Funding; Pharmacyclics: Research Funding. Mark:Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Research Funding, Speakers Bureau; Bristol Myers Squibb: Speakers Bureau. Stockerl-Goldstein:Janssen: Speakers Bureau. Usmani:Novartis: Speakers Bureau; Pharmacyclics: Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Millenium: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Array: Research Funding; Skyline: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Britsol-Myers Squibb: Consultancy, Research Funding; Onyx: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; BioPharma: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Londhe:Janssen Scientific Affairs, LLC: Employment. Etheredge:Janssen Research & Development, LLC: Employment. Parros:Janssen Research & Development, LLC: Employment. Fleming:Janssen Global Services, LLC: Employment. Liu:Janssen Research & Development, LLC: Employment. Freeman:Janssen Scientific Affairs, LLC: Employment. Ukropec:Janssen Scientific Affairs, LLC: Employment. Lin:Janssen Scientific Affairs, LLC: Employment. Lonial:BMS: Consultancy; Novartis: Consultancy; Celgene: Consultancy; Janssen: Consultancy; Onyx: Consultancy; Merck: Consultancy; Onyx: Consultancy; Janssen: Consultancy; BMS: Consultancy; Celgene: Consultancy; Millenium: Consultancy; Novartis: Consultancy.

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