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

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.

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Examining the Clinical Features and Underlying Cardiovascular Risk Among Patients with Polycythemia Vera in the REVEAL Study

Blood ◽

10.1182/blood.v128.22.1934.1934 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1934-1934 ◽

Cited By ~ 1

Author(s):

Brady L. Stein ◽

Ahmad Naim ◽

Michael R. Grunwald ◽

Alison R. Moliterno ◽

Stephen T. Oh ◽

...

Keyword(s):

Risk Factors ◽

Board Of Directors ◽

Research Funding ◽

Clinical Characteristics ◽

The United States ◽

Employment Equity ◽

Advisory Committees ◽

Reveal Study ◽

History Of ◽

Equity Ownership

Abstract Background:Patients with polycythemia vera (PV) often present with a broad range of clinical characteristics that may contribute to increased risks of cardiovascular (CV) morbidity and mortality, including thrombotic events (TE). Limited contemporary real-world data have been reported about the clinical burden of PV and treatment patterns in the United States. The ongoing REVEAL study collects data on disease burden, clinical management, patient-reported outcomes, and healthcare resource utilization for patients with PV in the United States. This analysis reports clinical characteristics, including underlying CV risk factors, for patients enrolled in the REVEAL study as of April 28, 2016. Methods: REVEAL is a multicenter, nonrandomized, prospective, observational study enrolling patients ≥18 years of age with a PV diagnosis who are actively managed in an academic or community setting. For this analysis, data regarding PV disease and diagnosis, clinical characteristics, and treatment patterns were collected at enrollment during usual-care visits and were based on physician assessment, electronic medical records, and local laboratory values. Ten-year CV risk factors selected for this analysis were adapted from the Framingham Heart Study for CV diseases. Results: At data cutoff, 2307 patients were available for this analysis. Mean (SD) age was 66.3 (12.2) years, 54.4% were male, 89.9% were white, 62.7% had at least some college education, and 51.1% were retired. Approximately 6% of patients had a family history of PV, primarily in parents (35.1%) and siblings (33.8%). A history of second malignancies was reported for 344 patients (14.9%). The majority of patients (84.6%) were diagnosed with PV based on an abnormal blood test alone or in combination with a bone marrow test. Among patients who were diagnosed with a mutational test (n=1078), 95.2% were diagnosed via an abnormal JAK2V617F test result. Abnormal hemoglobin (57.3%), hematocrit (55.4%), or both (47.5%) were among the most common blood values assessed for PV diagnosis. At diagnosis, 58.5% of patients were classified with high-risk PV (age ≥60 years or history of a TE); this percentage increased to 77.3% at REVEAL enrollment. The average (SD) disease duration from diagnosis to enrollment was 5.8 (6.1) years. At enrollment, 91.5% of patients were under active management for PV (phlebotomy ± aspirin, 34.0%; hydroxyurea ± aspirin, 27.0%; and phlebotomy + hydroxyurea ± aspirin, 23.2%). Underlying CV risk factors that were either diagnosed or treated in 86.0% of enrolled patients included hypertension (66.5%), history of smoking (46.2%), current smoking at enrollment (10.9%), obesity (34.2%), hyperlipidemia (27.4%), and diabetes (14.8%). At enrollment, 431 (18.7%) patients reported having ≥1 TE, including 181 patients who had a TE between PV diagnosis and enrollment. Venous and arterial TEs were reported in 11.1% and 8.6% of patients, respectively. Most commonly reported venous TEs were deep vein thrombosis (5.9%) and pulmonary embolism (2.5%); most common arterial TEs were cerebrovascular arterial thrombosis including transient ischemic attack (5.1%) and acute myocardial infarction (1.7%). Increased rates of TEs were observed among patients with hyperlipidemia (23.6%) and hypertension (21.0%; Table 1), compared with patients who did not have any risk factors (10.5%). Conclusion: A large proportion of patients in the REVEAL study had 1 or more underlying CV risks, including age, hypertension, smoking, obesity, hyperlipidemia, and diabetes, which may contribute to the risk of thrombosis. Longitudinal data from REVEAL will provide a better understanding of how these factors affect CV outcomes over time. Disclosures Stein: Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding. Naim:Incyte Corporation: Employment, Equity Ownership. Grunwald:Janssen: Research Funding; Forma Therapeutics: Research Funding; Medtronic: Equity Ownership; Alexion: Membership on an entity's Board of Directors or advisory committees; Ariad: Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Oh:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; CTI: Research Funding. Paranagama:Incyte Corporation: Employment, Equity Ownership. Cordaro:Incyte Corporation: Employment, Equity Ownership. Sun:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Boccia:Celgene: Consultancy, Honoraria, Speakers Bureau; Amgen/Onyx: Consultancy, Honoraria, Speakers Bureau; Gilead: Speakers Bureau; Genentech: Consultancy, Honoraria, Speakers Bureau; Eisai: Consultancy, Honoraria, Speakers Bureau. Mesa:Ariad: Consultancy; CTI: Research Funding; Gilead: Research Funding; Galena: Consultancy; Novartis: Consultancy; Promedior: Research Funding; Celgene: Research Funding; Incyte Corporation: Research Funding.

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

Blood ◽

10.1182/blood.v122.21.1146.1146 ◽

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.

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Disease and Clinical Characteristics of Patients with Polycythemia Vera: An Early View of the Reveal Study

Blood ◽

10.1182/blood.v126.23.2813.2813 ◽

2015 ◽

Vol 126 (23) ◽

pp. 2813-2813

Author(s):

Brady Stein ◽

Alison Moliterno ◽

Ralph V. Boccia ◽

Ahmad B. Naim ◽

Joseph A. Cordaro ◽

...

Keyword(s):

Research Funding ◽

Clinical Characteristics ◽

Thromboembolic Event ◽

Employment Equity ◽

Advisory Committees ◽

Reveal Study ◽

Patient Reported ◽

The Us ◽

History Of ◽

Equity Ownership

Abstract Background: Patients with polycythemia vera (PV) have an increased symptom burden (eg, fatigue, pruritus, and splenomegaly-related symptoms) and an increased risk of mortality compared with the general population, often resulting from thrombotic events, disease transformation to myelofibrosis, or secondary malignancies. There are limited data regarding PV burden and treatment patterns in a contemporary, real-world US setting. REVEAL is an ongoing observational study being conducted to describe contemporary demographics, burden of disease, clinical management, patient-reported outcomes, and healthcare resource utilization among patients with PV in the US. The objective of this assessment is to describe the clinical characteristics at enrollment among patients currently enrolled in REVEAL (enrollment from July 22, 2014 to June 9, 2015). Methods: REVEAL is a multicenter, noninterventional, nonrandomized, prospective, observational study. Eligible patients are ≥18 years of age with a PV diagnosis and currently under active management by a physician in the US. Data regarding disease and clinical characteristics, patient-reported outcomes, and health resource utilization are being collected at usual-care visits over a planned 36-month observation period. Analyses of these preliminary data were descriptive. Results: At data cutoff, 865 patients were enrolled (total planned enrollment, n=2000) from 174 sites (academic, n=27; community, n=147). Median (range) age at enrollment was 67 (22-95) years, 55.5% were male, 89.5% were white, and 45.4% had a history of smoking. Most patients (99.4%) had health insurance, including Medicare (56.0%), PPO (24.3%), or HMO (11.6%). Fifty-two percent were retired, 29.6% were employed, and 4.5% were unable to work or disabled. A total of 40.2% of patients completed a college/graduate degree, 19.9% had some college, and 32.5% completed high school or the equivalent. Documented major World Health Organization diagnostic criteria included JAK2V617F mutation in 50.9% of patients, elevated hemoglobin in 52.3%, and red cell mass in 5.5%. A bone marrow biopsy was conducted in 24.0% of patients, approximately half of whom (52.4% of the 24.0%) had trilineage myeloproliferation. Erythropoietin levels were abnormal in 19.7% of patients. Approximately half (46.6%) of patients had physician-reported PV-related symptoms at diagnosis, most frequently fatigue (25.2%) and pruritus (14.0%). At enrollment, median disease duration was 52.6 months; 42.3% of patients were diagnosed ≥5 years before enrollment. The most common comorbidities were hypertension (51.3%), obesity (14.2%), dyspnea (13.4%), myalgia (11.2%), and diabetes mellitus (11.1%). Mean hematocrit was 44.9%, hemoglobin was 14.5 g/dL, white blood cell count was 11.4×109/L, platelet count was 363.7×109/L, and absolute neutrophil count was 363.7×109/L. Twenty-one percent of patients had a history of thrombotic events, with 13.1% and 8.6% of patients experiencing ≥1 venous or arterial thromboembolic event, respectively. Of the 261 reported thrombotic events, 43.7% occurred after diagnosis of PV. The most common PV symptoms recorded at enrollment (using the Myeloproliferative Neoplasm Symptom Assessment Form) were fatigue (37.1%), pruritus (24.0%), headache (18.6%), insomnia (17.0%), dizziness (13.2%), bone pain (10.5%), and blurred vision (7.9%); 19.7% of 518 evaluable patients had palpable splenomegaly. Fewer than half of patients were receiving aspirin at enrollment (47.7%). The most common PV treatments ± aspirin were phlebotomy (PBT; 63.5%), hydroxyurea (HU; 42.2%), watchful waiting (5.3%), and ruxolitinib (3.1%); 23.0% of patients received PBT + HU. Conclusion: The REVEAL study is unique in that it captures data from both academic and community centers, and therefore includes a broader segment of the PV population typically not described in the literature. REVEAL can provide novel insights into questions related to the contemporary demographics of PV, practice patterns regarding diagnosis and therapy, and the real-world burden of PV and its impact on patients' quality of life and work productivity. Preliminary descriptive data from this early subset of patients suggest that a high proportion of patients report having PV-related symptoms at diagnosis, fewer patients are treated with aspirin than expected, and that thromboembolic event rates remain high after diagnosis. Disclosures Stein: Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees. Moliterno:Incyte Corporation: Membership on an entity's Board of Directors or advisory committees. Boccia:Incyte Corporation: Honoraria. Naim:Incyte Corporation: Employment, Equity Ownership. Cordaro:Incyte Corporation: Employment, Equity Ownership. Peng:Incyte Corporation: Employment, Equity Ownership. Sun:Incyte Corporation: Employment, Equity Ownership. Parasuraman:Incyte Corporation: Employment, Equity Ownership. Mesa:Promedior: Research Funding; Novartis Pharmaceuticals Corporation: Consultancy; NS Pharma: Research Funding; CTI Biopharma: Research Funding; Gilead: Research Funding; Pfizer: Research Funding; Incyte Corporation: Research Funding; Genentech: Research Funding.

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Patterns of Care of Aged Chronic Lymphocytic Leukemia Patients in the United States: Systematic Analysis of 457 Patients in the Connect CLL Registry

Blood ◽

10.1182/blood.v124.21.4672.4672 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4672-4672

Author(s):

Chadi Nabhan ◽

Natalie Galanina ◽

Neil E. Kay ◽

Anthony R. Mato ◽

David L. Grinblatt ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

The United States ◽

Initial Therapy ◽

Patterns Of Care ◽

First Line ◽

Employment Equity ◽

Advisory Committees ◽

Equity Ownership ◽

Baseline Characteristics

Abstract Introduction: The median age at diagnosis for CLL pts in the US is 72 years. As clinical trials in CLL have largely enrolled younger pt populations, data on disease and pts' characteristics, patterns of care, prognosis, and molecular features in aged CLL pts are limited. With this in mind, we conducted a prospective study to update critical demographic data and patterns of care for aged CLL pt. Patients and Methods: Connect®-CLL is a US-based prospective, longitudinal, multi-center, observational registry that is aimed at understanding patterns of CLL management without a study-specific intervention. We enrolled pts treated at an academic (n=155) or community (n=1340) setting between 2010 and 2014. Eligible pts were adults with a clinical diagnosis of CLL who required therapy 2 or less months after enrollment. Data on demographics, baseline characteristics, and treatment selection are presented here using descriptive statistics. Continuous variables are reported using appropriate measures of dispersion and central tendency (means, medians, ranges and standard deviations) while categorical variables are summarized as number and percentage of the analysis population. Results: Of 1495 enrolled pts, 457 (30.5%) were ≥75 years (57.3% males, 94.2% white). Rai stage III/IV was noted in 33% and B symptoms (predominantly fatigue (58.4%)) were observed in 68.1%. These and other clinical baseline characteristics appeared similar to pts younger than 75 years except that older pts had more prior malignancies (33.5% vs. 19.8%) and co-morbidities (69.3% vs. 53.6%). Cardiac, neurologic, and renal disorders were the most common morbidities in pts ≥75 years (11.5%, 8.8%, and 4.6% respectively). Imaging studies were performed in 157 (60.2%) older pts and in 416 (65.7%) pts less than 75 years prior to initial therapy. Percentage of pts with bulky nodes (> 5 cm) by imaging was similar in the two groups, 19.3% overall. Prognostic biomarker data were available on 247 pts (178 (72%) <75 years; 69 (28%) ≥75 years). While a higher proportion of older pts had CD38+ CLL (55.1% vs. 40.5%, P=0.038), the proportions of patients with ZAP-70+ CLL were similar between the two groups. In total, 137 (9%) older and 378 (25%) younger pts had 17p and 11q analysis by FISH at enrollment prior to first-line therapy. Of these, 27.0% of pts ≥75 years and 20.6% of pts <75 years had a deletion of either 17p or 11q (P=0.125). Out of all pts enrolled in the registry, 894 (60%) received first-line treatment (261 (29%) pts ≥75 years and 633 (71%) <75 years) as their indication for study entry. Amongst these treated pts, interim analysis shows (data cutoff date: 25 June 2014) progressive marrow failure was more commonly used as the indication for therapy in older pts compared to younger pts (52.1% vs. 38.5%; P<0.001), while splenomegaly was a more common cause for therapy in younger pts (16% vs. 9%; P<0.01). Rai stage III/IV at time of first therapy was 46% and 49% for younger and older pts, respectively. Progressive lymphocytosis was used as the indication for therapy in one third of pts regardless of age. Seventy-four percent of older CLL pts received first-line therapies containing rituximab (R) vs. 85% in pts <75 years (P<0.0001). R-bendamustine was the most common first-line regimen for CLL pts ≥75 (23.4%) while FCR was more commonly given to pts <75 years (32.5%). R-monotherapy was used in 18.8% of older pts versus 9.5% in pts <75 years (P<0.0001). Of note, approximately 25% of CLL pts ≥75 years did not receive R-based regimens for initial therapy. Conclusions: Connect®-CLL is the largest prospective, multicenter CLL registry in the United States. CLL Pts ≥75 years more frequently overexpress CD38 and may more commonly demonstrate high risk cytogenetics by FISH, although the difference did not reach statistical significance. Pts ≥75 years also more commonly had co-morbid diseases, and surprisingly 25% did not receive first-line R-based therapy. CLL pts are rarely included in front-line clinical trials (<3%). Given that novel therapies are increasingly available for CLL patients a continued analysis is warranted to determine their use in elderly vs younger patients as well. A longer follow up is needed to evaluate the impact of these findings on outcomes. Disclosures Nabhan: Celgene: Honoraria, Research Funding. Off Label Use: Lenalidomide in CLL. Kay:Celgene: Research Funding. Mato:Genentech, Celgene, Millenium: Speakers Bureau. Grinblatt:Celgene: Honoraria, Speakers Bureau. Kipps:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Lamanna:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Weiss:Celgene: Consultancy. Flinn:Celgene: Research Funding. Swern:Celgene: Employment, Equity Ownership. Street:Celgene: Employment, Equity Ownership. Kristen:Celgene: Employment, Equity Ownership. Flowers:Celgene, Prescription Solutions, Seattle Genetics, Millennium (unpaid), Genentech (unpaid) : Consultancy; Gilead, Spectrum, Millennium, Janssen: Research Funding.

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Lintuzumab and Low-Dose Cytarabine Compared to Placebo and Low-Dose Cytarabine in Patients with Untreated Acute Myeloid Leukemia (AML) 60 Years and Older: Results of a Randomized, Double-Blinded Phase 2b Study,

Blood ◽

10.1182/blood.v118.21.3613.3613 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3613-3613 ◽

Cited By ~ 4

Author(s):

Jeffrey E. Lancet ◽

Mikkael A. Sekeres ◽

Brent L. Wood ◽

Laurie E. Grove ◽

Larissa Sandalic ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Low Dose ◽

P Value ◽

Advisory Committees ◽

History Of ◽

Equity Ownership ◽

Double Blinded ◽

Low Dose Cytarabine

Abstract Abstract 3613 Background: Older adults with AML who decline intensive induction chemotherapy lack effective therapeutic options, as evidenced by a median overall survival (OS) of ∼5 months with low-dose cytarabine treatment (Burnett 2007). Leukemic blast cells express CD33 in most patients with AML. While antitumor activity has been previously demonstrated by CD33-directed agents, none of these are currently available. Lintuzumab (SGN-33) is a humanized antibody directed to CD33 that was studied in patients with myeloid malignancies and demonstrated tolerability with modest monotherapy activity. To determine if the addition of lintuzumab to low-dose cytarabine could prolong survival in older patients with untreated AML, a randomized, placebo-controlled, double-blinded phase 2b study was conducted (ClinicalTrials.gov #NCT00528333). Methods: The study was conducted at 72 international sites between November 2007 and August 2010. Patients were >60 years of age with centrally confirmed, previously untreated AML; the minimum blast percentage required was 20% with ≥50% CD33 expression. Maximum allowed WBC at baseline was 30,000/μL. All patients declined treatment with intensive induction chemotherapy. Cytarabine 20 mg was administered SC twice daily on Days 1–10 of each 28-day cycle (12 cycles maximum). Patients were randomized to additionally receive either lintuzumab 600 mg or placebo IV: in Cycle 1 on Days 1, 8, 15, and 22, and on Days 1 and 15 of subsequent cycles. Patients were stratified according to age, ECOG performance status (PS), and history of antecedent hematologic disorder (AHD). Cytogenetic risk was determined at baseline according to Fröling 2006. The primary endpoint of the study was OS, determined using an unstratified log rank test. Secondary endpoints included peripheral blood count recovery, transfusion requirements, infection rates, and quality of life. As patients choosing less-intensive therapy often incorporate quality of life into their treatment decision, follow-up bone marrow biopsies were not required in the study. Results: 211 patients were randomized in the study (107 lintuzumab arm, 104 placebo arm). The study arms appeared balanced; overall, the median patient age was 70 years (range 60–90), 53% were female, and baseline ECOG PS was 0/1 (55%) or 2 (45%). Baseline blast percentages were ≥30% in 74% of patients and 23% had a history of AHD. A median of 95% CD33 expression was documented at baseline in either bone marrow or peripheral blood. Median number of treatment cycles was 4 in the lintuzumab arm and 3 in the placebo arm. At the time of the analysis, 24 patients were alive and the maximum follow-up was 32 months. The estimated median OS for the lintuzumab + low-dose cytarabine arm was 4.7 months compared with 5.1 months for the placebo + low-dose cytarabine arm with a hazard ratio (lintuzumab to placebo) of 0.96, indicating that lintuzumab was not associated with a treatment effect (P value 0.76, 95% CI [0.72, 1.28]). Rates of infections or fevers of unknown origin requiring hospitalization or IV antibiotics did not differ between the study arms. Overall, 28% of patients were observed to have no peripheral blasts, ANC >1.0 x109/L, platelets >100 × 109/L, and no transfusions for at least 1 week. The median OS among all patients was 5.0 months, which was significantly impacted by cytogenetic risk (8.7 months for standard-risk compared with 4.5 months for high-risk; P value 0.0024). The incidence of adverse events (AEs) was comparable between the treatment groups, with the exception of infusion-related reactions which occurred more frequently in the lintuzumab arm. The most common ≥ Grade 3 non-hematologic AEs in the study were pneumonia (12%) and sepsis (8%). Conclusions: In this randomized, placebo-controlled, double-blinded phase 2b trial, the combination of lintuzumab and low-dose cytarabine did not improve OS compared with placebo and low-dose cytarabine. While lintuzumab was not effective, CD33 remains a compelling target for AML because it is widely expressed by malignant cells and appears to be absent from pluripotent hematopoietic stem cells. This was the largest study to date of patients treated with low-dose cytarabine; the median OS across both treatment arms was 5 months. A similar outcome was observed in the subgroup of patients with high-risk cytogenetics, confirming that low-dose cytarabine remains a valid comparator in trials of older patients with AML. Disclosures: Lancet: Seattle Genetics, Inc.: Research Funding. Off Label Use: Lintuzumab is an investigational monoclonal antibody directed against CD33. Sekeres:Celgene Corp.: Membership on an entity's Board of Directors or advisory committees; Celgene Corp.: Honoraria; Seattle Genetics, Inc.: Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees. Wood:Seattle Genetics, Inc.: Research Funding. Grove:Seattle Genetics, Inc.: Equity Ownership; Seattle Genetics, Inc.: Employment. Sandalic:Seattle Genetics, Inc.: Equity Ownership; Seattle Genetics, Inc.: Employment. Sievers:Seattle Genetics: Employment, Equity Ownership. Jurcic:Seattle Genetics, Inc.: Consultancy; Seattle Genetics, Inc.: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics, Inc.: Research Funding.

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Baseline Laboratory Parameters Potentially Associated with Thrombophilia in Patients with Chronic ITP.

Blood ◽

10.1182/blood.v120.21.2191.2191 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2191-2191

Author(s):

Raymond S.M. Wong ◽

Kalpana Bakshi ◽

Andres Brainsky

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Protein S ◽

Coagulation Cascade ◽

Published Data ◽

Employment Equity ◽

Advisory Committees ◽

Increased Risk ◽

History Of ◽

Equity Ownership

Abstract Abstract 2191 Background: The concept that chronic immune thrombocytopenia (cITP) may be pro-thrombotic has progressively gained acceptance as reports show an increased risk of thromboembolism (TEE) among cITP patients. A report from the Danish National Patient Registry showed an incidence of venous TEE of 5.32/1000 patient years (PYs) among cITP patients and 2.04/1000 PYs in a reference cohort (Severinsen 2010). Similar results were found in a US claims database study (Bennett 2008). ITP experts have gradually acknowledged this higher risk, but the reason for it is not understood. Many hematologic markers have been shown to be indicators of thrombophilia or activation of the clotting cascade (Jenkins 2012; De Stefano 2002; Tsai 2002); to our knowledge they have not been systematically and prospectively studied in cITP patients. Aim: Describe the frequency of potential laboratory predictors of thrombophilia in cITP. Methods: Adults with cITP were enrolled in an ongoing study to evaluate effects of eltrombopag on the bone marrow. A “thrombophilia panel” of suspected/known indicators of a thrombophilic state or activation of the coagulation cascade was collected at baseline. Patients could not have been treated with thrombopoietin receptor (TPO-R) agonists 6 months prior to enrollment. Patients with history of TEE and ≥2 risk factors for thrombosis were not eligible for enrollment. Results: Baseline thrombophilia panels were available for all 167 patients. Median age was 41 years; 108 (65%) patients were female. Approximately half of the patients were Caucasians (48.5%), while 31.1% and 19.2% had Central South and East Asian heritage. Median time since ITP diagnosis was 3.9 years (range, 0.2–45.7). Thirteen (8%) patients reported prior exposure to TPO-R agonists. Most patients (95%) had no family history of TEE and no patient had a history of TEE. Most patients (81%; Table 1) had abnormal levels of at least one well-known or suspected predictor of thrombosis or marker of activation of the coagulation cascade, and 93 (56%) had >1 abnormality. The most frequent abnormalities were elevated Factor VIII (48%), elevated d-dimer (32%), lupus anticoagulant (26%), and deficient protein S (22%; Table 2). Discussion: To our knowledge this is the only published prospective study of a thrombophilia profile in a cohort of cITP patients. Recently published data suggest that patients with cITP have a higher risk of TEE but no adequate explanation for this has been furnished. The fact that a high proportion of patients in this study had markers of thrombophilia or activation of clotting provides a working hypothesis that may at least partially elucidate this trait. Summary/conclusions: The multiple baseline abnormalities in possible predictors of thrombophilia may support the theory that ITP is pro-thrombotic, but they need to be assessed in and compared to the general population to allow proper understanding of their implications. The potential correlation of these abnormalities with TEE in this cohort will be reported upon study conclusion. Disclosures: Wong: GlaxoSmithKline: Research Funding; Pfizer: Research Funding; Biogen-Idec: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Bayer: Consultancy, Research Funding; Johnson & Johnson: Research Funding; MSD: Research Funding; Roche: Research Funding; Bristol-Myers Squibb: Research Funding. Bakshi:GlaxoSmithKline: Employment, Equity Ownership. Brainsky:GlaxoSmithKline: Employment, Equity Ownership, Patents & Royalties.

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Iron Deficiency Anemia in Infants and Toddlers – Role of Milk and Constipation

Blood ◽

10.1182/blood.v120.21.5171.5171 ◽

2012 ◽

Vol 120 (21) ◽

pp. 5171-5171

Author(s):

Madhavi Lakkaraja ◽

Lesley Small ◽

Maura Frank ◽

Aliza Solomon ◽

Nicole Kucine ◽

...

Keyword(s):

Iron Deficiency ◽

Board Of Directors ◽

Research Funding ◽

Deficiency Anemia ◽

Infants And Toddlers ◽

Iron Intake ◽

Advisory Committees ◽

Phone Calls ◽

History Of ◽

Equity Ownership

Abstract Abstract 5171 Introduction: One of the most common nutritional deficiencies in the world is iron-deficiency anemia and young children are at high risk of developing it. In spite of fortification of foods in the United States, there is a high prevalence of anemia in infants and toddlers increasing their risk of neuro-developmental effects. Constipation is defined as delay or difficulty in defecation ≥ 2 weeks. Around one year of age, various changes are commonly implemented in a child's diet including introduction of whole milk and solids. Children may then present with sub-clinical colitis, constipation and anemia secondary to blood loss in stool or develop anemia due to increased consumption of milk. The American Academy of Pediatrics (AAP) recommends screening for anemia at 1 year and 2 year visits. The only clue to intolerance to milk may be symptomatic constipation and treating the anemia and switching the type of milk often helps to resolve this problem. This study explores the relation between iron deficiency, constipation and milk. Methods: This is an ongoing prospective study, which has been extended from Cornell to different centers. Data presented here is only from the Cornell principal site. Children between 6 months and 30 months visiting the resident's pediatric clinic and having routine blood work drawn as a part of their visit were included in the study. The National Health Sciences (NHS) Constipation questionnaire was administered to the parents of these children; ≥ 2 was considered Constipation. In addition, a detailed diet history of the child, and history of medicines and illness was taken and questions were asked about family history of anemia, constipation and allergies. If the mother was breast feeding, questions were asked about her dairy intake. Comparisons were made between children with and without constipation/iron deficiency. If the child had Hemoglobin (Hgb) <11, the child was started on Iron as per clinic policy, and phone calls were made to check for compliance with Iron. In addition letters including a printed calendar and a note on Iron rich foods were mailed out to the parents. Results: Two hundred five children, 92 females and 113 males between 8 and 30 months mean age 16. 7 months, are enrolled in the study. Seventy-two children (35 %) were constipated (score ≥2). Forty-two children (20. 5%) had Hgb <11. Children who had Hgb < 11 were not more constipated (45%) than those who had Hgb ≥11 (35%). In the Hgb <11 group, there was no significant difference in Hgb between children with and without constipation (p = 0. 19), however there was a difference in Hgb between infants with a Constipation score 0 and score 1 (p = 0. 03). Of the 42 children who had Hgb <11, 3 were later found to have sickle trait or alpha thalassemia trait, which were identified when iron intake did not improve the Hgb level. Compliance with Iron: Of the 39 children who were on Iron, 9 parents could not be reached via phone. Only 6 parents gave no Iron at all but another 12 did not give Iron properly resulting in 18/30 or 60% of infants/toddlers not receiving an adequate trial of replacement Iron. Among the side effects of Iron, one parent felt Iron caused rash on back and wanted multivitamin with Iron after finishing a month's course, one child had discoloration of teeth, so the parent gave it with juice. Two parents with infants with apparent true milk protein allergy colitis said constipation improved with diet change and iron. Conclusions: The prevalence of mild anemia is high in infants and toddlers. There was no clear association of constipation and anemia. Compliance is one of the key factors for Iron replacement therapy and in view of how erratic compliance was, it is imperative to give proper instructions to the parent while prescribing Iron. Material to better indicate which foods were rich in iron and follow-up phone calls were included in the management to optimize iron intake of anemic children. We will include more patients, more closely monitor the change in the diet of the child, and monitor responses to Iron therapy in children with low Hgb. In addition, different practices at other involved centers e. g. Brooklyn hospital Center may allow comparison of the time of screening (9 months v/s 1 year) and testing with Hemoglobin/Hematocrit versus a full Complete Blood Count with indices. Disclosures: Bussel: Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cangene: Research Funding; GlaxoSmithKline: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Research Funding; IgG of America: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding; Eisai, Inc: Membership on an entity's Board of Directors or advisory committees, Research Funding; Shinogi: Membership on an entity's Board of Directors or advisory committees, Research Funding; Symphogen: Membership on an entity's Board of Directors or advisory committees; Sysmex: Research Funding; Portola: Consultancy.

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Defibrotide for the Treatment of Patients with Hepatic Veno-Occlusive Disease/Sinusoidal Obstruction Syndrome with/without Multi-Organ Dysfunction Following Chemotherapy: Results from an Ongoing Expanded Access Program

Blood ◽

10.1182/blood.v126.23.3121.3121 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3121-3121

Author(s):

Nancy A. Kernan ◽

Paul G. Richardson ◽

Angela R. Smith ◽

Brandon M. Triplett ◽

Stephan A. Grupp ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

The United States ◽

Occlusive Disease ◽

Sinusoidal Obstruction Syndrome ◽

Employment Equity ◽

Advisory Committees ◽

Kaplan Meier ◽

Equity Ownership ◽

Chemotherapy Patients

Abstract Introduction Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (VOD/SOS), is an unpredictable, potentially life-threatening complication of conditioning regimens for hematopoietic stem cell transplant (HSCT). Although VOD/SOS usually is thought of as a complication of HSCT, there is also a known risk in patients following chemotherapy in a non-HSCT setting. Severe hepatic VOD/SOS (ie, with multi-organ dysfunction [MOD]), may be associated with >80% mortality. Endothelial cell (EC) damage is a critical factor in the pathophysiology of VOD/SOS. Preclinical data suggest that defibrotide stabilizes ECs with direct, as well as EC-mediated, restoration of the thrombo-fibrinolytic balance. Defibrotide is approved for treatment of severe hepatic VOD/SOS in adult and pediatric patients in the European Union. In the United States, defibrotide is available as an investigational drug through an ongoing expanded-access protocol for treatment of hepatic VOD/SOS. Methods In the original protocol, patients were eligible if they had hepatic VOD/SOS by Baltimore criteria post-HSCT and MOD, defined by renal (tripling of creatinine levels or reduced creatinine clearance with or without dialysis) and/or pulmonary (need for oxygen supplementation with or without assisted ventilation) dysfunction. Symptoms of VOD/SOS were not considered adverse events (AEs) unless the event was considered serious. The protocol was later amended to include (1) post-chemotherapy patients with hepatic VOD/SOS; (2) patients with hepatic VOD/SOS without MOD, and (3) VOD/SOS per modified Seattle criteria. Enrolled patients received defibrotide 25 mg/kg/d in 4 divided doses for a recommended ≥21 days. Here, we describe efficacy and safety results with defibrotide for the subset of patients that developed VOD/SOS post-chemotherapy. Results Out of 642 patients who developed VOD/SOS and received ≥1 dose of defibrotide, 69 patients received chemotherapy without HSCT; 52% (n=36) had MOD, and 48% (n=33) did not. Median age was 8 years (range, <1 month-58.0 years), and 55 patients (80%) were ≤16 years (39 patients were children aged 2-11); 54% of patients were male. The most common primary diseases were acute lymphocytic leukemia (44%) and acute myelogenous leukemia (10%). Chemotherapeutic agents received by more than 30% of patients were vincristine, cyclophosphamide, cytarabine, doxorubicin, methotrexate and PEG-L-asparaginase. Antibody-drug conjugates linked to ozogamicin that are associated with development of VOD/SOS (gemtuzumab and inotuzumab) were received by 3 and 1 patient, respectively. The Kaplan-Meier estimated day +100 survival rate was 77.4% (95% confidence interval, 65.4%-85.7%). For patients with MOD and without MOD, the Kaplan-Meier estimated day +100 survival rates were 74.3% (56.4%-85.7%) and 80.9% (62.3%-90.9%), respectively. Overall, ≥1 AE was reported in 44 chemotherapy patients (63.8%). Of these, 14 (20.3%) had AEs assessed by the investigator as possibly, probably, or definitely related to defibrotide. Treatment-related AEs occurring in ≥2 patients were hypotension (4.3%), nausea (2.9%), vomiting (2.9%), and epistaxis (2.9%). Hemorrhagic AEs of any severity occurring in ≥2 patients were pulmonary (7.2%), epistaxis (5.8%), and gastric (2.9%). Serious AEs were reported in 26 patients (37.7%), most commonly multi-organ failure (7.2%), hypoxia (5.8%), and pulmonary hemorrhage (5.8%). AEs led to discontinuation in 4 patients (gastric, gastrointestinal and mouth hemorrhages, epistaxis, and hypotension). No treatment-related deaths were reported. Conclusions Day+100 survival of 77.4% in patients developing VOD/SOS following a variety of chemotherapy regimens without HSCT (80% of which were pediatric, primarily children) is a clinically encouraging finding. Defibrotide treatment in this group of 69 patients developing VOD/SOS post-chemotherapy was generally well-tolerated, with only 5.8% of patients discontinuing due to an AE and no treatment-related fatalities. Enrollment to the study continues. Support: Jazz Pharmaceuticals. Disclosures Kernan: Gentium S.p.A.: Research Funding. Off Label Use: Defibrotide is an investigational treatment for hepatic veno-occlusive disease/sinusoidal obstruction syndrome in the United States.. Richardson:Celgene Corporation: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Millennium Takeda: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. Grupp:Novartis: Consultancy, Research Funding. Antin:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Gentium S.p.A.: Membership on an entity's Board of Directors or advisory committees. Liang:Jazz Pharmaceuticals: Employment, Equity Ownership. Hume:Jazz Pharmaceuticals: Employment, Equity Ownership. Hannah:Jazz Pharmaceuticals: Consultancy. Nejadnik:Jazz Pharmaceuticals: Employment, Equity Ownership. Soiffer:Gentium SpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees.

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Pregnancy Management and Outcomes in Patients with Myeloproliferative Neoplasms

Blood ◽

10.1182/blood-2021-153887 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4615-4615

Author(s):

Iyad Arusi ◽

Vikas Gupta ◽

Ann Kinga Malinowski ◽

Nadine Shehata ◽

Dawn Maze

Keyword(s):

Observational Study ◽

Board Of Directors ◽

Pregnancy Outcomes ◽

Research Funding ◽

Myeloproliferative Neoplasms ◽

Driver Mutation ◽

Advisory Committees ◽

Consensus Recommendations ◽

Risk Patients ◽

History Of

Abstract Introduction: While BCR-ABL1 negative myeloproliferative neoplasms (MPN) are typically diagnosed in the sixth decade of life, approximately 20% of patients are diagnosed before the age of 40 years. Patients with MPN of reproductive age are being increasingly encountered in clinical practice. Concurrently, there has been increased awareness of the risks of pregnancy complications in patients with MPN and the importance of MPN-specific management to help mitigate these risks. MPN are associated with thrombotic and hemorrhagic complications, and pregnancy may amplify the thrombotic risk. Additionally, MPN may be associated with an increased risk of placental dysfunction and associated complications of preeclampsia, fetal growth restriction, preterm delivery and fetal loss. The aim of this observational study was to report on pregnancy outcomes in a modern cohort of patients with MPN managed according to consensus recommendations. Methods: We conducted a retrospective review of patients with MPN and pregnancy evaluated at either the Princess Margaret Cancer Centre or Mount Sinai Hospital in Toronto, Canada between January 1, 2010 and December 31, 2020. Diagnoses were defined according to the WHO 2016 criteria using information available from hospital records. Descriptive statistics were used to describe selected baseline characteristics. Categorical variables were summarized with counts and percentages. Results: A total of 32 patients with MPN and pregnancy were included in the study (Table 1). The median age at the time of the index pregnancy was 33 (range 21 - 45) years. The most common MPN diagnosis was essential thrombocythemia (ET, n=15), followed by polycythemia vera (PV, n=9) and primary myelofibrosis (PMF, n=8). Driver mutation data was available for 30 patients: 17 (57%) had mutated JAK2, 5 (17%) CALR, and 9 (30%) had no driver mutation identified. Five patients had a prior history of venous thrombosis, all of which were portal vein thrombosis, and 2 patients had a history of bleeding events. Information on antenatal treatment was available for 22 patients: 18 (82%) patients received aspirin, 3 (14%) received antenatal low molecular weight heparin (LMWH) and 3 (14%) received interferon (IFN; interferon alpha 2b in 2 cases and pegylated interferon alfa 2a in 1); 16 (73%) received post-partum LMWH. Information on maternal complications was available for 22 patients. There were 2 thrombotic events (1 antepartum and 1 postpartum) and 1 postpartum hemorrhage. There were no cases of preeclampsia. Of 22 pregnancies, there were 19 live births (86%), 2 first trimester losses (9%) and 1 second trimester loss (5%). Gestational age was 37 weeks or more in 16/17 (94%) and was 33 weeks for 1 patient. Vaginal deliveries were performed in 11/20 (55%) cases and 9/20 (45%) were Cesarean deliveries. Discussion: This observational study represents a modern cohort of MPN patients treated according to consensus recommendations. Our findings highlight that MPN patients have better pregnancy outcomes than those previously described in the literature. Limitations of this retrospective study include a small sample, missing data, and potential underreporting of early pregnancy loss. Pregnancy in patients with MPN is associated with unique risks that may be reduced with interventions such as antepartum aspirin, IFN in higher risk patients, and postpartum LMWH. That not all standard risk patients were managed with aspirin and postpartum LMWH suggests educational opportunities exist for hematologists and maternal-fetal medicine physicians involved in the care of these patients. Figure 1 Figure 1. Disclosures Gupta: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS-Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria; Pfizer: Consultancy; Roche: Consultancy; Constellation Pharma: Consultancy, Honoraria; Sierra Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding. Malinowski: Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy. Maze: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene-BMS: Honoraria; Takeda: Research Funding; PharmaEssentia: Research Funding; Kronos Bio: Research Funding.

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

Blood ◽

10.1182/blood-2021-151911 ◽

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 >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<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< 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<0.001), number of comorbidities (p< 0.001), bacteremia (p< 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.

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