Association of Hospitalization Due to Vaso-Occlusive Crisis with Subsequent Sickle Cell Disease-Related Organ Damage Hospitalization: Retrospective Analysis of 3-Year Observational Study Data

Abstract Background: Hospitalization due to vaso-occlusive crisis (H-VOC) is common in individuals with sickle cell disease (SCD), with an increasing occurrence of SCD-related complications, including organ damage, as the disease progresses. Evidence regarding the relationship between H-VOC and SCD-related organ damage, however, is lacking. Aim: To assess whether H-VOC is associated with hospitalization due to SCD-related organ damage, through retrospective analysis of data collected prospectively during a 3-year, multicenter, observational US study (NCT01220115) that aimed to better understand disease burden and management of SCD in individuals aged ≥2 years. Methods: Of the 498 individuals with SCD who were recruited into the US study, data were analyzed from 202 (100 men and 102 women) who were aged ≥16 years and had available hospital admission data. Organ damage was defined based on hospital discharge diagnosis. 1 Variables tested at baseline, in addition to H-VOC, included demographics, blood measures, and treatment history. Age and sex were included by default in all models based on literature suggesting they are relevant factors influencing organ damage. Hazard ratios (HRs) for the time from H-VOC to the first subsequent hospitalization due to SCD-related organ damage were estimated using multivariable Cox regression. Worsening of pre-existing organ damage was not considered as an event due to potential confounding (ie worsening of organ damage related to the pre-existing condition rather than as a consequence of the VOC). Results: During median 3-year follow-up, 55 (27%) individuals experienced at least one hospitalization due to SCD-related organ damage; 2 19 (9%) had multiple visits. Within the 12 months preceding baseline, 22 (11%) individuals had a history of organ damage, there was a median of two H-VOC in the 90 (45%) individuals with history of H-VOC, and 43 (21%) individuals had received chronic transfusion (≥6). History of H-VOC (HR 2.54, 95% confidence interval [CI] 1.46 to 4.43 in past 12 months), genotype (HR 2.69, 95% CI 1.34 to 5.41 for HbSS), and sex (HR 1.90, 95% CI 1.08 to 3.34 for women) were all significantly associated with subsequent hospitalization for SCD-related organ damage. Discussion and conclusion: This analysis demonstrates that history of H-VOC within the preceding 12 months is significantly associated with a higher rate of subsequent hospitalization due to SCD-related organ damage, independent of age, sex, and genotype, and may therefore help identify individuals at high risk of developing organ damage. Despite 21% of individuals receiving chronic transfusions at baseline, this factor did not remain significantly associated with the outcome when also considering genotype and H-VOC. Age and sex were unexpectedly insignificantly associated with the outcome; this is likely due to the relatively short follow-up time. Extending the historical timeframe of organ damage to 5 years did not change our findings, except that age also became significantly associated with subsequent hospitalization for organ damage. Acute chest syndrome and pneumonia were the most common types of historical (baseline) organ damage, whilst gallbladder disease was the most common organ damage observed during the follow-up period that was not observed at baseline. Our data have limited statistical power and generalizability; additional studies are required to confirm these findings. Nevertheless, our findings support the existing evidence of the impact that VOCs may have on individuals with SCD, and highlights the importance of preventing and reducing H-VOC. 1Acute chest syndrome or pneumonia; avascular bone necrosis of hip(s), shoulder(s) or spine; cardiac failure; central nervous system disease (ie abnormal transcranial Doppler, silent infarct, stroke and transient ischemic attack); gallbladder disease; leg ulcer; liver disease (ie hepatic fibrosis/ cirrhosis, hepatic sequestration/sickle-hepatopathy/intrahepatic sickling, pulmonary fibrosis, pulmonary hypertension); priapism; renal disease (ie acute renal failure, chronic renal failure-supportive, dialysis, microalbuminuria/ proteinuria, transplant); retinopathy; and splenic sequestration. 2The top 3 reasons for hospitalization due to SCD-related organ damage were acute chest syndrome or pneumonia (n=29; 53%), renal disease (n=7; 13%) and gallbladder disease (n=6; 11%). Figure 1 Figure 1. Disclosures Heeney: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; FORMA: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Vertex / Crispr Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; bluebird bio: Consultancy; Keros: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: DSMB; Cyclerion: Consultancy, Membership on an entity's Board of Directors or advisory committees. Pattipaka: Novartis: Current Employment, Current holder of individual stocks in a privately-held company. Fermont: Novartis Pharma AG, Basel, Switzerland: Current Employment, Current equity holder in publicly-traded company.

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The Impact of Hemoglobin Level on Risk of End-Organ Damage among Patients with Sickle Cell Disease - A Large-Scale, Longitudinal Analysis

Blood ◽

10.1182/blood-2020-140572 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 27-28 ◽

Cited By ~ 1

Author(s):

William B Ershler ◽

Laura M De Castro ◽

Zahra Pakbaz ◽

Aaron Moynahan ◽

Derek Weycker ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Large Scale ◽

Organ Damage ◽

Cell Disease ◽

Publicly Traded ◽

Advisory Committees ◽

Lower Odds ◽

Patient Demographics ◽

History Of

Background: Sickle cell disease (SCD) is an inherited, chronic, and multifaceted condition. Anemia affects most patients with SCD, and low hemoglobin (Hb) levels have been demonstrated to be correlated with end-organ damage (EOD) such as stroke, chronic kidney disease (CKD), end-stage renal disease (ESRD), and pulmonary hypertension (PH). This study sought to estimate the relationship between Hb and risk of EOD based on large-scale, longitudinal analyses of recent data. Methods: Patients with SCD aged 12 years and older and at least 1 Hb level reported from January 2013 to March 2019 in the large, US-representative, provider-centric Symphony Health claims database were included. For each qualifying patient, Hb values were identified and included as separate observations. Onset of new EOD, including stroke, CKD (including ESRD), and PH were ascertained during the 1-year period after the date of each Hb assessment (index date). History of EOD and other comorbid conditions were identified using claims from the database start date (January 1, 2012) or first activity date, whichever was later, up to the index date, to differentiate from newly diagnosed EOD. Patient demographics and clinical characteristics were summarized descriptively. Bivariate analyses of Hb levels and EOD were assessed using generalized estimating equations (GEE) regression with a logistic link function to account for clustering of observations at the patient level. Multivariable GEE regression was employed to evaluate the independent association between Hb and EOD, adjusting for patient demographics and other SCD complications. Results: A total of 16,754 patients with SCD aged 12 years and older were identified (mean age: 34.7 years, 37.7% male), contributing 41,692 observations of Hb levels (mean [SD], 9.8 [2.0] g/dL). In univariate analyses, higher Hb levels were significantly associated with lower odds of new EOD of any type (Figure). In multivariable analyses, after controlling for age, gender, and history of other SCD complications, patients with Hb b %12 g/dL had significantly lower odds of new EOD versus patients with Hb <7 g/dL (reference group): any of the 3 types of EOD by 63% (P<0.001), CKD by 64% (P<0.001), and PH by 79% (P<0.001). Patients with Hb b %10 g/dL also had significantly lower odds of stroke (by 34% [P=0.026]) versus patients with Hb <7 g/dL (Table). In addition to lower Hb, patients of older age, those who were publicly insured versus commercially insured, and patients with cardiovascular comorbidities (eg, heart failure or myocardial infarction) or other SCD chronic conditions generally had significantly higher odds of new EOD, regardless of type. Previous CKD and stroke were statistically and significantly associated with presence of new EOD of any type and with any of the other 2 types of EOD studied (previous CKD and new PH: P<0.01, new stroke: P<0.05; previous stroke and new CKD: P<0.01, new PH: P<0.05). Conclusions: In this large-scale, longitudinal analysis, a significant reduction in the risk of new EOD was observed among SCD patients with higher Hb levels. History of any EOD significantly correlated with presence of new EOD. New SCD treatments that can increase Hb levels can potentially offer clinical and economic value. Disclosures Ershler: Pharmacosmos Therapeutics Inc: Consultancy, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. De Castro:GlycoMimetics: Membership on an entity's Board of Directors or advisory committees; FORMA Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees. Pakbaz:Amgen: Membership on an entity's Board of Directors or advisory committees; Dova: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Terumo BCT: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Global Blood Therapeutics: Speakers Bureau. Moynahan:Global Blood Therapeutics: Research Funding; Novartis: Research Funding; Policy Analysis Inc.: Current Employment. Weycker:Policy Analysis Inc.: Current Employment, Current equity holder in publicly-traded company; Global Blood Therapeutics: Research Funding; Novartis: Research Funding. Pham:Policy Analysis Inc.: Current Employment; Global Blood Therapeutics: Research Funding; Novartis: Research Funding. Delea:Policy Analysis Inc.: Current Employment, Current equity holder in private company; Global Blood Therapeutics: Research Funding; Novartis: Research Funding. Agodoa:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company. Cong:Global Blood Therapeutics: Current Employment, Current equity holder in publicly-traded company.

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Preliminary Results of a Phase II Study to Determine the Safety of Defibrotide in Children and Adolescents with Sickle Cell Disease-Associated Acute Chest Syndrome (IND 127812)

Blood ◽

10.1182/blood-2020-139617 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 8-9

Author(s):

Jordan Milner ◽

Deborah Friedman ◽

Marise D'Souza ◽

Krishnan Sankaran ◽

Liana Klejmont ◽

...

Keyword(s):

Chest Pain ◽

Pulmonary Function ◽

Board Of Directors ◽

Research Funding ◽

Pulmonary Infiltrate ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Advisory Committees ◽

The Us

Background: Sickle cell disease (SCD) is a vasculopathy resulting in recurrent vaso-occlusive crises leading to endothelial dysfunction, chronic end-organ damage, poor quality of life, early mortality and the major curative therapy to date is allogeneic stem cell transplantation (AlloSCT) (Talano/Cairo, EJH, 2015). Acute chest syndrome (ACS) can result in pulmonary hypertension and is the leading cause of morbidity and mortality in patients with SCD (Gladwin et al, NEJM, 2008). ACS accounts for 25% of deaths (Vichinsky et al, Blood, 1997). Clinical definition of ACS is chest pain, fever, cough, dyspnea, and new pulmonary infiltrate on chest radiography. Defibrotide was approved in the US for the treatment of severe sinusoidal obstructive syndrome (SOS) with renal or pulmonary dysfunction following HSCT (Cairo et al, BJH, 2020). Defibrotide primarily targets endothelium in microvascular beds and has anti-inflammatory and anti-coagulant activity, which can treat the underlying pathophysiology of ACS (Falanga et al, Leukemia, 2003 and Scallia et al, Clin Pharm, 1996 and Pescador et al, Vasc Pharm, 2013). Objective: To determine the safety and toxicity of defibrotide in children, adolescents, and young adults with SCD-associated ACS. Design/Methods: Patients with SCD aged 2 to 40 years meeting ACS criteria (at least two of the following: fever, chest pain, cough, dyspnea, tachypnea, pulmonary infiltrate on chest imaging, decreased oxygen saturation with or without supplemental oxygen requirements) and eligibility were enrolled within 72 hours of diagnosis after consent was obtained (NCT03805581). Baseline studies comprised of chest radiograph, CT chest angiogram, echocardiography with TRJ velocity and brachial artery reactivity, pulmonary function tests, and biomarkers (IFN-a and -g, TNF-a, IL-6, 8, and 10, sCD163, TSP-1, secretory phospholipase A(2), sVCAM-1, sTNFR1, Ang2, sTei-2, PAI-1, sICAM-1, sP-and sE-selectin, sPECAM-1, VEGF-A, C, D and sVEGFR1 and 2). Defibrotide was administered at 6.25mg/kg IV q6 hours and continued for 7 days or until time of discharge, whichever occurred earlier and patients were followed until day +30 following defibrotide. Dose limiting toxicities include Grade III/IV infusion/allergic reaction or hemorrhage probably or directly related to defibrotide. Results: We have enrolled thirteen patients aged 3 to 18 years with a gender ratio (M/F) of 4/9. Patients' genotypes are as follows: hemoglobin SS disease in nine patients, hemoglobin SC disease in two patients, and hemoglobin Sb0/+ thalassemia in two patients. Presenting symptoms included fever, chest pain, cough, dyspnea, tachypnea, pulmonary infiltrate on imaging, and hypoxia.Eight patients completed seven days of treatment, one patient received 6 days of treatment, three patients were discharged after three days of treatment, and one patient withdrew due to recurrent fevers unrelated to defibrotide. All but one patient had resolution of fevers prior to end of treatment. Patients required an average of 1.15 days of oxygen support, with one patient requiring high flow nasal cannula, and no patients required mechanical ventilation. There were no adverse events possibly, probably, or directly related to defibrotide. There was no evidence of hemorrhage in any patient despite four patients receiving concomitant ketorolac or ibuprofen. Of the eleven patients who had pulmonary infiltrates on imaging, eight were evaluated on day +30, two had complete resolution of infiltrate, five had improvements, and one had no change. Seven patients did not follow-up for echocardiography or pulmonary function testing and two of those patients were unable to be evaluated at day +30 due to COVID-19. Discussion: The preliminary data suggest defibrotide is safe and well tolerated in patients with SCD-related ACS. All patients at diagnosis have had baseline studies, which included biomarkers; however, only eight of the thirteen patients have completed all required observations due to poor compliance. After four patients were enrolled and three failed to follow-up, changes to appointment schedules were made with detailed information on all follow-ups. Efforts at improving compliance post therapy are ongoing. Further accrual is needed to determine clinical significance of improvements in cardiac and/or pulmonary function. This study was funded in part by a grant from Jazz Pharmaceuticals. Disclosures Cooke: Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding, Speakers Bureau. Cairo:Nektar Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Technology Inc/Miltenyi Biotec: Research Funding; Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Miltenyi: Research Funding. OffLabel Disclosure: Defibrotide is utilized in patients with acute chest syndrome to decrease the amount of time they are hospitalized and to assist in alleviating symptoms. Defibrotide is approved in the US for sinusoidal obstructive syndrome with renal or pulmonary dysfunction.

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Safety and Efficacy of Venetoclax-Based Treatment in Elderly CLL Patients: A Retrospective Study from the Filo Group

Blood ◽

10.1182/blood-2021-149640 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3747-3747

Author(s):

Charlotte Doublet ◽

Marie-Sarah Dilhuydy ◽

Emmanuelle Ferrant ◽

Pierre Feugier ◽

Alexandra Fayault ◽

...

Keyword(s):

Retrospective Study ◽

Board Of Directors ◽

Research Funding ◽

Progression Free Survival ◽

Oncology Nurses ◽

Advisory Committees ◽

Free Survival ◽

Daily Dose ◽

History Of

Abstract Median age at diagnosis of chronic lymphocytic leukemia is 72 years. However, only few patients over 80 years of age are included in clinical trials, even in those devoted to unfit patients. In order to evaluate both efficiency and safety of venetoclax in this category of patients, we conducted a multicentric retrospective study and collected data from 77 CLL patients from 19 FILO centers who started venetoclax after 80 years of age. Median age at venetoclax initiation was 86 years old (81-97). 63% of patients had a history of heart disease, 62% had renal failure (moderate 59% and severe 3%) and 29% had a history of severe infections. Despite their comorbidities and a CIRS greater than 6 in 70% of cases, their autonomy was preserved with a median performans status of 1 (0-4). In this comorbid geriatric population, pretherapeutic geriatric assessment was only performed in a single patient. The median number of prior therapies was 2 (0-6) with an exposure to a BCR inhibitor in 56% of cases. 11q and 17p deletion were found in 39% and 30% of cases respectively, 39% of patients had a complex karyotype and 30% harbored a TP53 mutation. However, in this real life population, these prognostic factors were only performed in half of patients. IGHV mutational status was only available in 11 patients, and 83% of them had unmutated IGHV. At the time of venetoclax initiation, the tumor lysis syndrome (TLS) risk was moderate in 57% of cases and high in 8% of cases. Venetoclax was administered as a single agent (42%) or in association with rituximab (58%). In total, half of the patients were hospitalized at each dose ramp-up, and only 3 patients were treated on outpatient basis. 82% of the cohort was able to reach the daily dose of 400mg. Half of the patients were included in a phone call monitoring program with oncology nurses to pre-emptively manage side effects and foster therapy adherence. The safety study reported 14% of TLS, with 2 discontinuations of treatment within the first month: one of which led to dialysis and the other to death. As in the previously published studies, 25% of patients had infectious complications, and grade 3 haematological and digestive toxicities were reported in 42% and 22% of cases, respectively. The reduction of the daily dose of venetoclax was necessary for 33%. Permanent discontinuation of venetoclax occurred in 40% of subjects, including 29% of early withdrawal (within the first 3 months). Main reasons for discontinuation were intolerance (21%), CLL progression (21%), death (21%) and scheduled treatment discontinuation (10%). The overall response rate was 86%, consisting of 49% of complete response (unconfirmed by bone marrow biopsy) and 37% of partial response. With a median follow-up of 21months, estimated progression free survival and overall survival were 29 and 38 months respectively. Prior exposure to a BCR inhibitor had no impact on progression free survival. To conclude, venetoclax has a manageable safety profile in elderly patients with comorbidities and can induce prolonged responses. Finally, if additional follow-up by oncology nurses seems to be more and more implemented, the pre-therapeutic onco-geriatric evaluation remains underexploited in this population. Disclosures Ferrant: AstraZeneca: Honoraria; AbbVie: Honoraria, Other: Travel, Accommodations, Expenses; Janssen: Other: Travel, Accommodations, Expenses. Feugier: Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Amgen: Honoraria; Astrazeneca: Consultancy, Honoraria. Laribi: AstraZeneca: Other: Personal Fees; Le Mans Hospital: Research Funding; AbbVie: Other: Personal Fees, Research Funding; Jansen: Research Funding; Novartis: Other: Personal Fees, Research Funding; IQONE: Other: Personal Fees; Astellas Phama, Inc.: Other: Personal Fees; BeiGene: Other: Personal Fees; Takeda: Other: Personal Fees, Research Funding. Tchernonog: JANSSEN: Consultancy; ABBVIE: Consultancy; ASTRAZENECA: Consultancy. Dartigeas: Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Abbvie: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress; Janssen: Membership on an entity's Board of Directors or advisory committees, Other: travel grants/Congress. Quinquenel: Abbvie: Honoraria; Janssen: Honoraria; AstraZeneca: Honoraria.

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Connect MM®—the Multiple Myeloma (MM) Disease Registry: Incidence of Second Primary Malignancies (SPM)

Blood ◽

10.1182/blood.v124.21.4749.4749 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4749-4749

Author(s):

Robert M. Rifkin ◽

Rafat Abonour ◽

Jatin J. Shah ◽

Jayesh Mehta ◽

Mohit Narang ◽

...

Keyword(s):

Multivariate Analysis ◽

Board Of Directors ◽

Solid Tumor ◽

Research Funding ◽

Significant Risk ◽

Significant Risk Factor ◽

Prior History ◽

Advisory Committees ◽

History Of

Abstract Background: Increased rates of SPM have been observed as newer cancer treatments have improved survival over the past 2 decades (Fraumeni et al. NCI, 2006). Higher incidence of specific types of hematologic SPM following MM, especially acute myeloid leukemia and myelodysplastic syndromes, have been reported relative to the general population (Dores et al. NCI, 2006; Mailankody et al. Blood, 2011; Ravazi et al. Blood, 2011; Landgren and Mailankody. Leukemia, 2014). A complex interplay between myeloma-, host-, environmental-, and treatment-related factors likely contributes to the increased incidence of SPM in MM. Connect MM is the first and largest prospective, observational, US-based, multicenter registry designed to characterize patients (pts), treatment patterns, and outcomes in newly diagnosed MM (NDMM) pts. Methods: Between September 2009 and November 2012,a total of 1493 NDMM pts were enrolled from 234 US sites within 2 mos of the first diagnosis of MM. Patient data were collected at baseline and each subsequent quarter using a standardized form. Invasive SPM included hematologic and solid tumor second cancers and non-invasive SPM were defined as non-melanoma skin cancers (NMSC). SPM incidence and incidence rate (IR; number of pts with SPM per 100 patient-yrs [PY]) were calculated for all pts and by exposure to specific treatments, including lenalidomide (LEN). PYs were calculated as the observation period from the start of treatment until the detection of the first reported SPM (per category), death, or end of follow-up (pt lost or data cutoff). Results: As of Dec 10, 2013, SPM data were available for 1493 NDMM pts. The median age was 67 yrs (range, 24-94 yrs), 82% of patients were white and 57% were male. Median follow-up was 29.0 mos (0-49 mos). The median OS of treated pts was 44.4 mos. Fifty pts did not receive treatment and had no SPM reported. A total of 74 of the 1443 treated pts (5.1%) reported SPM. Invasive SPM were observed in 51 pts (3.5%): 37 pts (2.6%) with solid tumors and 14 pts (1.0%) with hematologic SPM. Lung/bronchus and myelodysplastic syndromes were the most frequently reported solid tumor and hematologic SPM respectively. NMSC were reported for 26 pts (1.8%). 3 pts had both an invasive SPM and NMSC. The IRs for invasive, hematologic, and solid tumor SPM by LEN exposure are listed in Table 1. By multivariate analysis, the only significant risk factor for the occurrence of SPM was prior history of invasive malignancy. Demographics (including age, ethnicity, race, and gender), International Staging System stage, family history of myeloma or other cancers, history of smoldering MM or monoclonal gammopathy of unknown significance, or prior radiation therapy were not associated with the occurrence of SPM. Conclusions: This analysis shows that there was no increased risk of invasive SPM in this disease-specific registry of pts with NDMM. The risk of SPM for LEN exposed pts was not greater than that for pts not exposed to LEN. In addition, multivariate analysis indicated the only significant risk factor for SPM was prior history of invasive malignancy. As additional agents are approved for the treatment of MM and the length of pt survival increases, longer prospective observation with expanded enrollment on the registry will better characterize the occurrence of SPM in this pt population. Correlations with risk factors including age, pre-existing MDS, risk status, as well as type and duration of therapy will continue to be investigated. Table 1. Incidence rates (per 100 PYa) by treatment exposure IR per 100 PY (95% CI) SPM LEN-Exposed (n = 977) Non–LEN Exposed (n = 466) Invasive 0.85 (0.61-1.19) 1.16 (0.72-1.86) Hematologic 0.17 (0.08-0.36) 0.47 (0.22-0.99) Solid tumor 0.67 (0.46-0.98) 0.68 (0.36-1.26) NMSC 0.50 (0.32-0.77) 0.41 (0.18-0.91) a PY of exposure is the sum of exposure of all pts. Disclosures Rifkin: Celgene Corp: Consultancy; Millenium: Consultancy; Onyx: Consultancy; Takeda: Consultancy; Amgen: Consultancy. Abonour:Celgene Corp: Honoraria, Speakers Bureau. Shah:Celgene Corp: Consultancy, Research Funding. Mehta:Celgene Corp: Consultancy, Speakers Bureau. Narang:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Terebelo:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Gasparetto:Celgene: Consultancy, Honoraria; Millenium: Honoraria. Thomas:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Toomey:Celgene Corp: Membership on an entity's Board of Directors or advisory committees. Hardin:Celgene Corp: Research Funding. Lu:Celgene Corp: Employment. Kenvin:Celgene Corp: Employment. Srinivasan:Celgene Corp: Employment, Equity Ownership. Ricafort:Celgene Corp: Employment. Nagarwala:Celgene Corp: Employment. Durie:Celgene Corp: Expert Board Committee Other; IRC Onyx: Membership on an entity's Board of Directors or advisory committees; DMC Millennium: Membership on an entity's Board of Directors or advisory committees; IRC J&J: Membership on an entity's Board of Directors or advisory committees.

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Sickle-Cell Disease Patients' Attitudes Towards Their Treatment with Hydroxycarbamide

Blood ◽

10.1182/blood-2019-125673 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1013-1013

Author(s):

Frédéric Galactéros ◽

Ersi Voskaridou ◽

Anoosha Habibi ◽

Giovanna Cannas ◽

Laure Joseph ◽

...

Keyword(s):

Sickle Cell Disease ◽

Board Of Directors ◽

Sickle Cell ◽

Research Funding ◽

Fetal Hemoglobin ◽

Treatment Discontinuation ◽

Cell Disease ◽

Advisory Committees

Hydroxyurea (HU) is approved in the EU and USA for prevention of vaso-occlusive crises (VOC) including acute chest syndromes (ACS) in patients over 2 years with sickle-cell disease (SCD). The major benefits of HU in SCD are directly related to its abilities to increase HbF, decrease sickling of red blood cells and hemolysis, leading to reduction of vaso-occlusive episodes, need for blood transfusions and consequently reduction of morbidity and mortality. Adherence to the treatment is paramount for effectiveness, but in spite of proven benefits, barriers to adherence persist.[1] ESCORT-HU study (European Sickle Cell Disease COhoRT - HydroxyUrea), is a multicentric, prospective, non-interventional European study designed to evaluate the safety profile of HU in real life. Patients were enrolled from January 2009 to June 2017 with a follow-up of up to 10 years. All interruptions and resumptions of HU treatment exceeding 15 days were recorded in this study. We hereby present the analysis of the group of patients who self-discontinued HU at least once during the study before informing their caregiver, with a view to identify potential barriers to long-term adherence. In total, 1906 patients were enrolled in ESCORT-HU from 63 centers in France, Germany, Greece and Italy. Of these, 619 patients (32%) stopped HU for over 15 days at least once, and around a third (11% of all patients) were due to patient's will. The mean duration of HU treatment before the first discontinuation was 4.8 ± 5.1 years. Data are summarized in table 1. Compared to the rest of the cohort, the 'treatment discontinuation' group had similar distribution by gender and indication for HU prescription, but a higher proportion of adults stopped HU more than 15 days. It is notable that the proportion of patients with SC genotype was higher in the 'treatment discontinuation' group (4.5% vs 1.7%). The patients in the 'treatment discontinuation' group had more frequent SCD symptoms before enrolment in the study (table 2). Hematological and clinical improvement compared to the baseline was observed in both groups. However, average mean Corpuscular Volume (MCV) and Fetal Hemoglobin percentage (HbF%) were lower and mean percentages of patients with SCD symptoms were higher over the three years of follow-up in the 'treatment discontinuation' group, suggesting that HU daily dose was insufficient (table 2). Sixty patients have no treatment resumption date reported which suggest a permanent interruption of their treatment. Among them 32% preferred to switch to another HU medicinal product and 13% have safety issue (table 3). Understanding and managing self-discontinuation of HU before taking medical advice is challenging for the physician. It is tempting to speculate that it may be due, at least in part, to lack of effectiveness potentially due to an underdosage of the treatment. Resistance to the treatment may also be suggested based on past literature data revealing a great variability in the response (determined by HbF%) to HU therapy. There is evidence that genetic modifiers affect individual response to HU.[2],[3] Finally, weariness from long-term use may also explain the patient's wish to discontinue HU. But treatment at optimal effective should be the primary goal of caregivers. [1]Smaldone A., Manwani D., Green NS, Greater number of perceived barriers to hydroxyurea associated with poorer health-related quality of life in youth with sickle cell disease, Pediatr Blood Cancer. 2019 [2] Steinberg MH, Voskaridou E, Kutlar A, Loukopoulos D, Koshy M, et al. (2003). Concordant fetal hemoglobin response to hydroxyurea in siblings with sickle cell disease. Am J Hematol 72: 121-126 [3] Ware RE, Despotovic JM, Mortier NA, Flanagan JM, He J, et al. (2011) Pharmacokinetics, pharmacodynamics, and pharmacogenetics of hydroxyurea treatment for children with sickle cell anemia. Blood 118: 4985-4991 Disclosures Galactéros: Addmedica: Membership on an entity's Board of Directors or advisory committees. Voskaridou:Celgene Corporation: Consultancy, Research Funding; Protagonist: Research Funding; Genesis: Consultancy, Research Funding; Acceleron: Consultancy, Research Funding; Addmedica: Membership on an entity's Board of Directors or advisory committees. Cannas:Addmedica: Membership on an entity's Board of Directors or advisory committees.

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Real World Evidence of Prescription Patterns and Effect of Oxbryta (voxelotor) for Patients with Sickle Cell Disease

Blood ◽

10.1182/blood-2020-143434 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 31-32

Author(s):

Nirmish Shah ◽

Ahmar Urooj Zaidi ◽

Michael U. Callaghan ◽

Darla Liles ◽

Clarissa E. Johnson ◽

...

Keyword(s):

Clinical Trial ◽

Board Of Directors ◽

Sickle Cell ◽

Real World ◽

Research Funding ◽

Cell Disease ◽

Advisory Committees ◽

Real World Evidence ◽

Disease Modifying

Background: Sickle cell disease (SCD) is a chronic illness characterized by anemia, recurrent severe pain and recurrent organ damage, affecting approximately 100,000 persons in the United States. Prior to November 2019, FDA approved SCD disease-modifying treatments included only hydroxyurea (HU) and L-glutamine. However, voxelotor (Oxbryta®) was recently approved under an accelerated approval based on the HOPE study for the treatment of adult and pediatric patients with SCD 12 years of age and older. We aimed to provide real world evidence of the types of patients prescribed voxelotor and preliminary evidence of potential treatment effects. Methods: Patient records were reviewed from five medical centers with comprehensive sickle cell care. All patients prescribed voxelotor from Nov 25, 2019 to July 31, 2020 were included in our analysis. Data reviewed included: patient demographics, hydroxyurea use, as well as pre- and post- voxelotor changes on red cell transfusion number, vaso-occlusive crisis (VOC) and hemoglobin (Hb) values. In addition, voxelotor dosage changes, side effects, and patients perception on impact on their health were recorded. Descriptive and summary statistics were used to provide results. Results: We reviewed data from 60 patients (18 pediatric and 42 adult), across the five centers, who were prescribed voxelotor. Mean age was 33 (SD 13.8) years old with 63% female patients. All patients were African-American/Black and 96% were HbSS (2% Hb SC and 2% HbSOArab). Eighty (80)% were on hydroxyurea, 20% were on chronic transfusions, and 10% were on erythropoietin stimulating agents when prescribed voxelotor. Mean baseline hemoglobin during the 3 months prior to initiation was 7.38 g/dL (SD 1.46) with all patients started at the recommended dose of 1500mg. Annualized VOC events for the year prior to starting voxelotor was 0.62 (SD) or 7.44 VOCs per year. Across all sites, 31 patients were prescribed voxelotor but had either not initiated drug, not returned for follow up labs at time of analysis, or refused to take drug once approved (n=1). Nine patients had only 1 month of follow labs to review and an additional 18 patients with 3 months of follow up labs. These 27 patients were followed for an average of 6.0 months (SD 7.7) on treatment with 4 patients (15%) requiring dose adjustment to 1000mg. Dose adjustments were for side effects including abdominal pain, diarrhea, loose stools and nausea/vomiting. One patient had dosing changed from daily to three times a day. Average hemoglobin during steady state after 1 and 3 months of treatment were 8.6 g/dL (SD 1.8) and 8.0 g/dL (SD 1.8), respectively. In addition, 52% increased by 1g/dL at 1 month (n=21) and 44% increased by 1g/dL at 3 months (n=18). The mean maximum hemoglobin obtained during the 3-month period following initiation of voxelotor was 8.9 (SD 2.1) g/dL. During follow up visits, several patients reported 'more energy' and improvement in 'morning achiness' and 'quality of life', while a few patients noted no change in stamina or well-being. Three patients (5%) had drug discontinued due to becoming pregnant, unexplained elevation of liver enzymes, and due to excessive abdominal pain and nausea. Annualized VOC rates after voxelotor initiation were numerically decreased, although limited by short follow up. Conclusion: We present real world evidence of prescribing patterns and initial outcomes from the use of newly approved voxelotor. We found the majority of patients prescribed voxelotor were the HbSS genotype, on hydroxyurea, and with a mean baseline Hb <7.5 g/dL, indicating an initial focus on more anemic patients. Interestingly, one-fifth of the prescribed patients where on chronic transfusions. Consistent with the HOPE trial, the average Hb levels was found to have increased at 1 month and 3-month follow up. Our preliminary results support an overall increase in hemoglobin in patients treated with voxelotor and we aim to continue following patients over a longer follow up period. This provides important real-world evidence for this newly approved disease-modifying therapy for SCD. Disclosures Shah: Alexion: Speakers Bureau; CSL Behring: Consultancy; Novartis: Consultancy, Research Funding, Speakers Bureau; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau; Bluebird Bio: Consultancy. Zaidi:Global Blood Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Emmaus Life Sciences: Consultancy, Honoraria; Imara: Consultancy, Honoraria; bluebird bio: Consultancy, Honoraria; Cyclerion: Consultancy, Honoraria; Novartis: Consultancy, Honoraria. Callaghan:Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche/Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Research Funding; Sancillio: Other; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; NovoNordisk: Other, Speakers Bureau; Biomarin: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Site Investigator/sub-I Clinical Trial, Speakers Bureau; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other, Speakers Bureau; Alnylum: Current equity holder in publicly-traded company; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Spark: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Hema Biologics: Honoraria, Membership on an entity's Board of Directors or advisory committees. De Castro:Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; FORMA Therapeutics: Membership on an entity's Board of Directors or advisory committees; GlycoMimetics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

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Ponatinib In Patients (pts) With Chronic Myeloid Leukemia (CML) and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) Resistant Or Intolerant To Dasatinib Or Nilotinib, Or With The T315I BCR-ABL Mutation: 2-Year Follow-Up Of The PACE Trial

Blood ◽

10.1182/blood.v122.21.650.650 ◽

2013 ◽

Vol 122 (21) ◽

pp. 650-650 ◽

Cited By ~ 6

Author(s):

Jorge E. Cortes ◽

Dong-Wook Kim ◽

Javier Pinilla-Ibarz ◽

Philipp D le Coutre ◽

Ronald Paquette ◽

...

Keyword(s):

Board Of Directors ◽

Stock Options ◽

Research Funding ◽

Response Rates ◽

Advisory Committees ◽

Advisory Boards ◽

Common Drug ◽

Heavily Pretreated ◽

History Of

Abstract Background Ponatinib is a potent, oral, pan-BCR-ABL inhibitor with activity against native and mutant forms of BCR-ABL, including the tyrosine kinase inhibitor (TKI)-resistant T315I mutant. The efficacy and safety of ponatinib (45 mg orally QD) were evaluated in the phase 2, international, open-label clinical trial (PACE) in pts with CML or Ph+ ALL. Methods 449 pts resistant or intolerant (R/I) to dasatinib or nilotinib or with the T315I mutation confirmed at entry were enrolled. Five pts (3 CP-CML, 2 AP-CML) without confirmed T315I and not R/I to dasatinib or nilotinib were treated, but not assigned to a cohort; they were included in safety analyses only. The primary endpoint was major cytogenetic response (MCyR) at any time within 12 mos for CP-CML, major hematologic response (MaHR) at any time within 6 mos for advanced Ph+ leukemia. Data are as of 1 April 2013, with a median follow-up of 19 (0.1-30) mos, and 18 mos minimum follow-up for pts remaining on study. Results Median age was 59 (18-94) yrs; 53% were male. Median time from diagnosis to ponatinib was 6 (0.3-28) yrs. Pts were heavily pretreated: 96% received prior imatinib, 84% dasatinib, 65% nilotinib, 7% bosutinib; 58% received ≥3 TKIs. In pts previously treated with dasatinib or nilotinib (N=427), 88% had a history of resistance, 12% were purely intolerant to dasatinib or nilotinib. Best prior response to most recent dasatinib or nilotinib was 26% MCyR or better in CP-CML, 23% MaHR or better in advanced Ph+ leukemia. The most common BCR-ABL mutations at baseline were 29% T315I, 8% F317L, 4% E255K, 4% F359V, 3% G250E. No mutations were detected in 44% of pts (Sanger sequencing). At the time of analysis, 46% of pts remained on study (60% CP-CML). The most common reasons for discontinuation: progressive disease (20%), adverse events (AEs; 13%; most common was thrombocytopenia, 4%). Response rates are shown in the table. Response rates were higher in CP-CML T315I vs R/I cohorts, however, a post-hoc multivariate analysis previously showed that T315I was not an independent predictor of MCyR. Other features, especially higher dose intensity and younger age in T315I pts, may explain the higher response rates. In CP-CML, responses were deep and durable; 91%, 91%, and 75% of pts with MCyR, CCyR, or MMR, respectively, were estimated to remain in response at 12 mos; progression-free survival (PFS) and overall survival (OS) were estimated to be 80% (median 27 mos) and 94% at 12 mos, respectively; progression to AP/BP occurred in 3 CP-CML pts , 2 other pts with a history of AP re-entered AP. 49% of AP-CML pts with MaHR were estimated to remain in response at 12 mos (median 12 mos); PFS and OS were estimated to be 56% (median 14 mos) and 84% at 12 mos. 36% of BP-CML pts with MaHR were estimated to remain in response at 12 mos (median 5 mos); PFS and OS were estimated to be 18% (median 4 mos) and 30% (median 7 mos) at 12 mos. 8% of Ph+ ALL pts with MaHR were estimated to remain in MaHR at 12 mos (median 3 mos); PFS and OS were estimated to be 7% (median 3 mos) and 39% (median 8 mos) at 12 mos. The most common drug-related AEs (>30%) were thrombocytopenia (37%), rash (34%), and dry skin (32%). Pancreatitis was the most common drug-related serious AE (5%); it occurred early and was primarily managed with dose modification, 1 pt discontinued. Serious cardiovascular, cerebrovascular, and peripheral vascular AEs occurred in 6%, 3%, and 2% of pts (drug-related: 2%, 1%, 1%). Conclusions Ponatinib has substantial activity in these heavily pretreated Ph+ leukemia pts who have limited available treatment options, with a safety profile reflective of the population. Updated data with a minimum follow-up of 2 yrs will be presented. Disclosures: Cortes: Ariad, Pfizer, Teva: Consultancy; Ariad, BMS, Novartis, Pfizer, Teva: Research Funding. Kim:BMS, Novartis, IL-Yang: Consultancy; BMS, Novartis, Pfizer, ARIAD, IL-Yang: Research Funding; BMS, Novartis, Pfizer, IL-Yang: Honoraria; BMS, Novartis, Pfizer: Speakers Bureau; BMS, Pfizer: Membership on an entity’s Board of Directors or advisory committees. Pinilla-Ibarz:Novartis, Ariad: Research Funding; Novartis, Ariad, BMS and Pfizer: Speakers Bureau. le Coutre:Novartis: Research Funding; Novatis, BMS, Pfizer: Honoraria. Paquette:ARIAD, BMS, Novartis: Consultancy, Honoraria, Speakers Bureau. Chuah:Novartis, Bristol-Myers Squibb: Honoraria. Nicolini:Novartis, Ariad, Teva, Pfizer: Membership on an entity’s Board of Directors or advisory committees; Novartis, BMS, Teva: Speakers Bureau; Novartis, BMS, Teva, Pfizer, Ariad: Honoraria; Novartis & Bristol Myers Squibb: Research Funding; Novartis, Ariad and Teva: Consultancy. Apperley:Novartis: Research Funding; Ariad, Bristol Myers Squibb, Novartis, Pfizer, Teva: Honoraria. Talpaz:Ariad, BMS, Sanofi, INCYTE: Research Funding; Ariad, Novartis: Speakers Bureau; Ariad, Sanofi, Novartis: Membership on an entity’s Board of Directors or advisory committees. DeAngelo:Araid, Novartis, BMS: Consultancy. Abruzzese:BMS, Novartis: Consultancy. Rea:BMS, Novartis, Pfizer, Ariad, Teva: Honoraria. Baccarani:Ariad, Novartis, BMS: Consultancy; Ariad, Novartis, BMS, Pfizer, Teva: Honoraria, Speakers Bureau. Müller:Novartis, BMS, Ariad: Consultancy, Honoraria; Novartis, BMS: Research Funding. Gambacorti-Passerini:Pfizer: Research Funding; Pfizer, BMS: Honoraria. Lustgarten:ARIAD: employees of and own stock/stock options in ARIAD Pharmaceuticals, Inc Other, Employment. Rivera:ARIAD: Employment. Clackson:ARIAD: employees of and own stock/stock options in ARIAD Pharmaceuticals, Inc Other, Employment. Turner:ARIAD: Employment. Haluska:ARIAD: employees of and own stock/stock options in ARIAD Pharmaceuticals, Inc Other, Employment. Deininger:BMS, ARIAD, NOVARTIS: Consultancy; BMS, NOVARTIS, CELGENE, GILEAD: Research Funding; ARIAD, NOVARTIS: Advisory Boards, Advisory Boards Other. Hochhaus:Ariad, Novartis, BMS, MSD, Pfizer: Research Funding; Novartis, BMS, Pfizer: Honoraria. Hughes:Novartis, BMS, ARIAD: Honoraria, Research Funding. Goldman:Ariad: Honoraria. Shah:Ariad, Bristol-Myers Squibb: Consultancy, Research Funding. Kantarjian:ARIAD, Novartis, BMS, Phizer: Research Funding.

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French National Retrospective Cohort of Hairy-Cell Leukemias: Risk of Second Malignancies after 10 Years of Follow-up

Blood ◽

10.1182/blood-2019-127560 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1537-1537

Author(s):

Jérôme Paillassa ◽

Edouard Cornet ◽

Stephanie Noel ◽

Cecile Tomowiak ◽

Aline Schmidt ◽

...

Keyword(s):

Board Of Directors ◽

Research Funding ◽

Retrospective Cohort ◽

Hematological Malignancies ◽

Hematological Malignancy ◽

Solid Cancer ◽

Advisory Committees ◽

History Of ◽

History Of Cancer

Introduction: Hairy-cell leukemia (HCL) is a chronic B-cell lymphoproliferative disorder with a favorable outcome thanks to treatment with purine analogues (PNA) like cladribine and pentostatin. Here, we updated the French national retrospective cohort of HCL after 10 years of follow-up, in order to evaluate the risk of second cancers in these patients. Methods: Data were collected up to June 2018 through a questionnaire sent to the members of the Société Française d'Hématologie, and centralized in the cohort database. We described the second malignancies observed during the follow-up, distinguishing second 'solid' cancers from second hematological malignancies. Then, using a Fine and Gray model, we performed a multivariate analysis in order to identify second cancer risk factors. Finally, to evaluate the excess of cancers in our cohort in comparison with the French general population, we calculated the standardized incidence ratio (SIR). Results: 279 patients (pts) from 19 centers were included in our retrospective cohort. The median age was 59 years old (range 29-88). 21% had an infectious disease at diagnosis, 23% had a familial history of cancer and 11% a personal history of cancer before HCL diagnosis. The median number of lines of treatments was 1 (0-7). PNA (cladribine or pentostatin) were the first therapeutic choice in frontline (75% of pts) and at relapse (69%). With a median follow-up of 127 months (2-413), the median overall survival for the overall study population was 328 months (95% CI 299-357) and the median relapse-free survival (RFS) was 136 months (95% CI 109-163). Pts treated with cladribine or pentostatin in first line had a statistically significant better RFS than pts treated with 'other' treatments (log rank test, p < 0.001). The 10-year cumulative incidence of relapse was 39% (95% CI 33-46). Pts who received treatments other than PNA in first line had a higher risk of relapse (Gray's test, p < 0.001). For pts receiving PNA in first and second lines, there was no difference in outcomes between those who switched PNA and those who did not. In this cohort, we observed 68 second malignancies during the follow-up: 49 solid cancers (most prevalent: prostate and non-melanoma skin cancers) and 19 hematological malignancies (most prevalent: monoclonal gammopathy of undetermined significance (MGUS) and myelodysplastic syndromes (MDS)). The median onset of second cancer, second solid cancer and second hematological malignancy from HCL diagnosis was 81 months, 99 months and 78 months, respectively. The median age at diagnosis of cancer, solid cancer and hematological malignancy was 70, 69 and 77 years old, respectively. Considering death as a competing risk, the 10-year cumulative incidence of cancer, solid cancer and hematological malignancy was 15% (95% CI 11-19), 11% (95% CI 7.2-15), and 5.0% (95% CI 2.8-8.2), respectively. In multivariate analyses, IFN treatment was associated with a decreased risk for all cancers (Fine and Gray regression model, subdistribution Hazard Ratio (sdHR) 0.53 (95% CI 0.29-0.97); p = 0.038), a familial history of cancer was a risk factor for solid cancers (sdHR 2.12 (95% CI 1.15-3.91); p = 0.017), a personal history of cancer was a risk factor for hematological malignancies (sdHR 3.47 (95% CI 1.14-10.55); p = 0.028). Even after excluding non-melanoma skin cancers and MGUS, there was an excess of cancers (SIR = 2.22), solid cancers (SIR = 1.81) and hematological malignancies (SIR = 6.67). Conclusions: In this updated real-world retrospective cohort with a long follow-up and most pts treated with PNA, we highlighted the importance and the excess of second cancers in HCL patients, in particular hematological malignancies. Figure Disclosures Paillassa: Janssen: Other: Bibliography board with young hematologists. Thieblemont:Roche: Honoraria, Research Funding; Gilead: Honoraria; Novartis: Honoraria; Kyte: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Cellectis: Membership on an entity's Board of Directors or advisory committees. Hermine:AB Science: Membership on an entity's Board of Directors or advisory committees. Feugier:janssen: Honoraria, Research Funding, Speakers Bureau; gilead: Honoraria, Research Funding, Speakers Bureau; roche: Honoraria, Research Funding, Speakers Bureau; abbvie: Honoraria, Research Funding, Speakers Bureau. Troussard:Innate Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Other: Research Support; Sysmex: Other: Research Support.

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A Pilot Study of Eptifibatide for Treatment of Acute Pain Episodes in Sickle Cell Disease.

Blood ◽

10.1182/blood.v120.21.2102.2102 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2102-2102

Author(s):

Payal C Desai ◽

Julia Brittain ◽

Susan Jones ◽

Adam McDonald ◽

Douglas R Wilson ◽

...

Keyword(s):

Sickle Cell Disease ◽

Board Of Directors ◽

Sickle Cell ◽

Acute Pain ◽

Research Funding ◽

Point Estimate ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Opioid Use ◽

Advisory Committees

Abstract Abstract 2102 Background: Despite the abundant laboratory evidence of platelet activation and inflammation in sickle cell disease (SCD), the contribution of these changes to the pathogenesis of SCD remains uncertain. Patients with SCD exhibit increased platelet activation in the non-crisis, “steady state,” and further increases with acute pain episodes. In addition, levels of the inflammatory mediator, CD40 ligand (CD40L) are increased in the plasma and significantly reduced in the platelets of SCD patients compared to healthy individuals. CD40L may contribute to the pathogenesis of acute pain episodes. Despite an improved understanding of the pathophysiology of SCD, the treatment of acute pain episodes is supportive. We performed a randomized, placebo-controlled study to evaluate the safety and efficacy of eptifibatide, a synthetic peptide inhibitor of the glycoprotein (GP) IIb/IIIa receptor, in patients with SCD during acute painful episodes. Methods: In this single site placebo-controlled trial, eligible patients admitted for acute painful episodes received eptifibatide (two 180 mg/kg boluses 10 minutes apart, followed by a continuous infusion at 2 mg/kg/min for 6 hours) or placebo at a ratio of 2:1. The Post-Treatment Phase lasted for up to 7 days or until resolution of the crisis, whichever was shorter, but no less than 24 hours after discontinuation of infusion. The Follow-up Phase included safety evaluations obtained 14 to 17 days and 28 to 35 days after discontinuation of infusion. The primary outcomes were major bleeding episodes and the largest observed decrease in platelet count during the study. We also evaluated the effect of eptifibatide on the duration of acute pain episodes, pain intensity, duration of hospitalization, total opioid use and acute chest syndrome. Results: Thirteen patients (SS - 10, Sb0 - 2, SC - 1) were randomized to receive either eptifibatide (N=9; 6 females; median age - 25 years) or placebo (N=4; 3 females; median age - 31 years). One patient in the eptifibatide arm withdrew consent following completion of study drug infusion and 1 patient in the placebo arm was withdrawn early because she did not meet eligibility criteria. In the intent-to-treat analysis, there were no major bleeding episodes in either group (point estimate of difference in eptifibatide vs. placebo proportion: 0.0, 95% CI; −0.60, 0.37).There was one minor bleeding episode in a patient on the eptifibatide arm (point estimate of difference in eptifibatide vs. placebo proportion: 0.11, 95% CI: −0.502, 0.494). There was a trend for the largest decrease in platelet count to be greater in the eptifibatide arm compared to the placebo arm, although the difference was not statistically significant (Hodges-Lehman estimate of location shift for eptifibatide vs. placebo: −82, 95% CI; −281, 54). There was no significant difference in the proportion of patients with thrombocytopenia between the treatment groups (point estimate of difference in eptifibatide vs. placebo proportion: 0.11, 95% CI: −0.587, 0.495). The median time to discharge and the median time to crisis resolution were 3.0 days for both treatment arms. The median total opioid use was 400.2 morphine equivalents (ME) for the eptifibatide group and 1471 ME for the placebo group (Hodges-Lehman estimate of location shift for eptifibatide vs. placebo: −65.8, 95% CI: −2519, 1700). There was one episode of acute chest syndrome in each treatment arm. Conclusions: In this small study of SCD patients hospitalized with acute painful episodes, eptifibatide appeared to be safe, but did not improve the times to crisis resolution or hospital discharge. Eptifibatide was associated with a reduced requirement for opioid analgesics, although the difference was not statistically significant. Clinicaltrials.gov Identifier: NCT00834899. Disclosures: Parise: BD: Consultancy; Biogen-Idec: Consultancy; NIH: Research Funding; AHA: Research Funding; SCDAC-NIH: Membership on an entity's Board of Directors or advisory committees; BRI Milwaukee: Membership on an entity's Board of Directors or advisory committees. Ataga:Pfizer: Consultancy; HemaQuest Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adventrx Pharmaceuticals: Consultancy. Off Label Use: Eptifibatide, a glycoprotein IIb/IIIa inhibitor, was evaluated as treatment for acute pain episodes in patients with sickle cell disease.

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Prevalence and Risk Predictive Factors of Comorbid Malignancies in Patients with Chronic Myeloid Leukemia

Blood ◽

10.1182/blood.v128.22.1900.1900 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1900-1900

Author(s):

Tong-Yoon Kim ◽

Sung-Eun Lee ◽

Soo-Hyun Kim ◽

Soo-Young Choi ◽

Eun-Jung Jang ◽

...

Keyword(s):

Board Of Directors ◽

Medical Records ◽

Myeloid Leukemia ◽

Research Funding ◽

Hodgkin’S Lymphoma ◽

Hodgkin's Lymphoma ◽

Advisory Committees ◽

History Of

Abstract Introduction: As chronic myeloid leukemia (CML) patents are generally diagnosed at old age and live longer by active use of BCR-ABL1 tyrosine kinase inhibitors (TKIs), the occurrence of other malignancy (OM) is becoming a critical issue as a long-term comorbidity. An increased rate of OM has been reported in myeloproliferative disorders and long-term TKI treatment may induce OM in CML. To explore exact prevalence and characteristics of OM, we reviewed medical records of CML patients and compared with those of age-matched Korean population. Methods: The medical records of 1,469 CML patients who diagnosed between January 2000 and December 2014 were reviewed using Korean data-set of Asia CML Registry (ACR). With a cut-off date of July 2016, age-standardized prevalence rates (A-SPR) of OM (except benign tumors and other leukemias) were analyzed and compared with that of general population in Korea Central Cancer Registry (KCCR). In addition, we analyzed cumulative incidence rate of OM and various risk factors. Results: The median duration of follow-up was 84 (1-197) months, and 96 CML patients had at least one OM. Forty three patients had a history of OM before a median 69 (1-161) months of CML diagnosis and 53 patients developed OM after a median 53 (range; 0.2-172) months of CML diagnosis. The OM included 32 thyroid cancers, 19 colorectal cancers, 16 stomach cancers, 9 breast cancers, 4 gynecological cancers (3 cervical cancers and 1 uterine endometrial cancers), 3 lymphoma (2 non-Hodgkin's lymphoma and 1 Hodgkin's lymphoma), 3 biliary cancer, 3 skin cancers, 3 prostate cancers, 2 lung cancer, 2 tongue cancer, 2 liver cancer, 2 esophageal cancer, 1 pancreatic cancer, and 1 bladder cancer.A-SPR of OM was 1.7 times higher in CML patients. Hodgkin's lymphoma (8.7 times), thyroid cancer (2.6 times), biliary cancer (2.6 times), colorectal cancer (2 times), non-Hodgkin's lymphoma (1.8 times), cervical cancer (1.8 times), and breast cancer (1.6 times) had a higher A-SPR. On the other hands, skin cancer (3.3 times), lung cancer (2 times), and liver cancer (2 times) were lower than that of general population. With 53 patients who had OM after CML diagnosis, we analyzed the cumulative incidence. The risk of OM was increased over the follow-up period (2.7% at 7 years) Univariate analysis revealed that patients who were more than 37 years old at CML diagnosis (4.3% vs. 0.4%, p<0.001) and who had family history of cancer (8.2% vs. 2.3%, p=0.002) were associated with a higher OM. After adjusting for factors, multivariate analysis showed that older age (HR of 4.19, P<0.001) and family history (HR of 3.17, P=0.001) were independently associated with increased risk. There was no difference in 7-year overall survival (OS) between patients with OM (n=96) and without OM (n=1,373) (84.9% vs. 86.9%, p=0.573). However advanced cancer stages (stage 3 and 4) of OM significantly affected poor OS ( 88.3% vs. 65.6% P=0.0406). Conclusion: Although comorbid malignancies did not significantly affect CML survival, poor survival in advanced stages and the high risk of other cancers warn the need of systematic screening in long-term CML survivors. In addition, the specific cancer types with a significantly higher A-SPR should be considered for further studies including genetic mechanisms. Disclosures Kim: ILYANG: Consultancy, Honoraria, Research Funding; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

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