scholarly journals Real-World Use of Therapeutic Anticoagulation in Patients with Paroxysmal Nocturnal Hemoglobinuria. Results of a Survey of Physicians in Australia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4537-4537
Author(s):  
Jeffrey Szer ◽  
Cecily J Forsyth ◽  
Anja Giese
Keyword(s):  
Board Of Directors ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Primary Prophylaxis ◽  
Secondary Prophylaxis ◽  
Prior History ◽  
Advisory Committees ◽  
Vein Thrombosis ◽  
Therapeutic Anticoagulation ◽  
Increased Risk ◽  
History Of

Abstract Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening hematopoietic stem cell disorder characterized by uncontrolled complement-mediated hemolysis. Patients with PNH are at increased risk of thromboembolism and premature death. This risk is predominantly due to the effects of chronic hemolysis and platelet activation. Eculizumab, a monoclonal antibody that inhibits terminal complement activation, has been shown to reduce hemolysis and dramatically reduce the rate of thromboembolism. A previous publication (Kelly et al, 2011) suggested that cessation of therapeutic anticoagulation (TAC) in PNH patients on eculizumab with no prior history of thrombosis is safe. There are very few reports on the outcomes of cessation of TAC in PNH patients on eculizumab who have a prior history of thrombosis or on the use of non-vitamin K antagonist oral anticoagulant (NOAC) agents in PNH patients with a history of thrombosis. In Australia, patients with PNH are predominantly managed by individual hematologists rather than at a single centre and hence anticoagulation practices following the introduction of eculizumab therapy are variable. We surveyed Australian hematologists managing eculizumab-treated patients with PNH to obtain the details of anticoagulation management and incidence of thrombotic events in their patients. We received responses from 30 hematologists caring for a total of 58 patients with PNH on eculizumab (1-17 patients per hematologist) and the table summarises the results. TAC as primary prophylaxis had been ceased in 10 patients with no recurrent thrombotic events. One (1) patient remains on primary prophylaxis due to persistently high D-dimer and factor VIII levels. TAC for secondary prophylaxis had been ceased in 2 patients due to bleeding (1 patient with subdural hematoma, 1 patient with gastrointestinal bleeding) and neither of these patients had a further thrombotic event. One patient, with a prior history of thrombosis, requested cessation of TAC and subsequently developed a provoked thrombosis. Three patients not receiving TAC when eculizumab was commenced developed thrombosis; two (2) patients had provoked deep venous thromboses and one patient developed a splanchnic vein thrombosis following a cholecystectomy in association with severe sepsis. One patient had a portal vein thrombosis immediately prior to commencing eculizumab therapy but has never received TAC due to severe coexistent thrombocytopenia from myelodysplasia. This patient has not had a recurrent thrombosis. Three (3) patients with thrombotic events prior to eculizumab therapy (1 patient with pulmonary emboli, 1 patient with cerebral venous sinus thrombosis and 1 patient with inferior vena cava thrombosis) had anticoagulant therapy changed from warfarin to rivaroxaban. At a follow-up of at least twelve months for all 3 patients there have been no recurrent thrombotic events and no bleeding complications. In conclusion, these Australian data are consistent with those reported by Kelly suggesting that cessation of primary prophylaxis in PNH patients on eculizumab is safe. Cessation of TAC in PNH patients on eculizumab with a prior thrombosis can be considered if there are clear contraindications to anticoagulation. Thromboprophylaxis in situations of increased risk of venous thromboembolism remains essential for all PNH patients not on TAC, even when they are on eculizumab therapy. The three patients on rivaroxaban as secondary prophylaxis are, to our knowledge, the first reported patients with PNH treated on a NOAC. Table. Number of patients New thrombotic events Eculizumab treated 58 Ceased TAC: Total1. As 1o prophylaxis2. As 2o prophylaxis(i) Due to bleeding(ii) At patient request 1410431 -None-None1 (provoked) TE in patients not on TAC at commencement of eculizumab 3 3 (provoked) NOAC as 2o prophylaxis 3 None Disclosures Szer: Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Alexion Australia: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Shire: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Forsyth:Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Giese:Alexion: Employment.

Long Term Treatment with Eculizumab In Paroxysmal Nocturnal Hemoglobinuria (PNH): Sustained Efficacy and Improved Survival

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 639-639 ◽  
Author(s):  
Richard J Kelly ◽  
Anita Hill ◽  
Lindsay D Mitchell ◽  
Stephen John Richards ◽  
Louise M Arnold ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Bone Marrow Failure ◽  
Primary Prophylaxis ◽  
Advisory Committees ◽  
Transfusion Requirements ◽  
Long Term Treatment ◽  
Impact On Survival ◽  
History Of ◽  
Age And Sex

Abstract Abstract 639 PNH is an acquired clonal hemolytic anemia associated with severe symptoms, life-threatening thrombosis, pulmonary hypertension (PH), chronic renal impairment (CRI) and bone marrow failure resulting in reduced quality of life (QoL) and survival (median: 10 – 15 years). Eculizumab is a monoclonal humanized antibody that inhibits terminal complement activity and thereby prevents intravascular hemolysis, reduces transfusions, improves QoL and protects against PH, CRI and thromboses. Eculizumab was approved for PNH in 2007 as a result of studies with short follow-up and with no information on it's impact on survival. We present data on 79 patients treated with eculizumab from the Leeds PNH Center between May 2002 – July 2010 including 34 patients from the clinical trials and a further 45 treated since, funded in England by the National Commissioning Group (NCG) or locally in Scotland and Wales. The NCG indications for treatment include transfusion-dependent hemolysis (4 or more transfusions in 12 months) or significant PNH-related complications (i.e. thrombosis or renal failure) regardless of transfusion history. Three patients did not fulfil these criteria but were treated for profound symptoms as agreed with the NCG. Forty men and 39 women were treated for a mean of 39 months (1-98). Median age at diagnosis was 37yo (12-79) and at initiation of eculizumab was 46yo (14-84). Median granulocyte clone size at the start of eculizumab was 96.38% (41.78-99.98). Patient survival on eculizumab was compared with age and sex matched controls obtained using data from the UK Office of National Statistics. We previously published that there was a significantly worse survival for PNH patients compared to matched controls with ~ 50% of patients dying as a result of PNH (Hillmen et al., NEJM 1995). In the current series there was no difference in mortality between patients on eculizumab and the normal population (P=0.46; Fig 1). Patients over 70yo had worse survival (P=0.0042) with none of the 45 patients under the age of 50yo dying. Three patients died: a 55yo man from metastatic caecal carcinoma diagnosed prior to eculizumab, a 76yo woman who died from pneumionia following a long history of recurrent bronchopneumonia prior to eculizumab and a 79yo man with a preceding history of ischaemic heart disease who died from cardiac failure. Three patients have had a clonal evolution of their PNH, 1 to acute myeloid leukemia and 2 to myelodysplasia. Two patients have stopped eculizumab: - 1 due to pre-existing aplastic anemia and 1 with spontaneous remission of his PNH. Seventy four patients remain on eculizumab to date.Figure 1Kaplan-Meier survival plots depicting PNH patients on eculizumab compared to age and sex matched controlsFigure 1. Kaplan-Meier survival plots depicting PNH patients on eculizumab compared to age and sex matched controls There were 34 thrombotic episodes in 21/79 patients (27%) prior to eculizumab and only 2 thromboses since. Importantly primary prophylaxis with warfarin has now been stopped in 21 patients (mean duration of 8.4 months (range: 1–25) and total of > 14 years) with no thromboses occurring. Seven patients had thrombosis within 12 months prior to starting eculizumab and they had no further thromboses on therapy. Therefore eculizumab is effective in preventing new, or evolution of pre-existing thrombosis, and appears to remove the need for primary prophylactic anticoagulation. We have not systematically stopped the anticoagulation of patients with a previous history of thrombosis. Patients had a mean of 19.9 units transfused (0-156) in the 12 months before eculizumab. Of the 64 patients on eculizumab for at least a year, 43 (67%) have been transfusion independent for >12 months. Twenty one patients still needing transfusions had a significant (P=0.028) reduction in their mean requirement of 24.6 (4-52) units in the 12 months before eculizumab compared to a mean of 14.6 (2-50) units in the last 12 months. Eculizumab is well tolerated long-term (> 8 years of therapy) with continued improvement in PNH associated symptoms, reduction in transfusion requirements and a higher proportion of transfusion independent patients than previously seen. There is a significant reduction in the development of thromboembolism on eculizumab therapy and importantly we have been able to stop primary prophylaxis with warfarin in 21 patients without any thrombotic complications. We demonstrate for the first time that eculizumab has a major impact on survival in PNH so that survival is comparable to an age- and sex-matched control population. Disclosures: Kelly: Alexion Pharmaceuticals: Honoraria. Hill:Alexion Pharmaceuticals: Honoraria, Speakers Bureau. Richards:Alexion Pharmaceuticals: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Arnold:Alexion Pharmaceuticals: Honoraria. Hillmen:Alexion Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Analysis of Second Primary Malignancies in Lenalidomide-Treated Patients with IPSS Low- or Int-1-Risk Myelodysplastic Syndromes

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1704-1704 ◽  
Author(s):  
Aristoteles Giagounidis ◽  
Azra Raza ◽  
Alan F. List ◽  
Pierre Fenaux ◽  
Bouchra Benettaib ◽  
...  
Keyword(s):  
Research Funding ◽  
Prior History ◽  
Second Primary ◽  
Employment Equity ◽  
Phase 3 ◽  
Advisory Committees ◽  
Increased Risk ◽  
History Of ◽  
Equity Ownership ◽  
Rbc Transfusion

Abstract Abstract 1704 Background: Lenalidomide (LEN) is approved in the US for the treatment of RBC transfusion-dependent patients with IPSS Low- or Int-1-risk myelodysplastic syndromes (MDS) with del(5q), with or without other cytogenetic abnormalities. In a phase 3 trial, treatment with LEN 5 mg and 10 mg resulted in RBC transfusion independence (TI) for ≥ 26 weeks in 43% and 56% of such patients, cytogenetic response in 25% and 50%, and a significant improvement of health-related quality of life (p <.05 for both 5 mg and 10 mg). Achievement of RBC-TI ≥ 8 weeks was associated with a significantly reduced risk of AML progression and death (p <.05 for both) (Fenaux P et al. Blood 2011;doi: 10.1182/blood-2011-01-330126). In newly diagnosed multiple myeloma patients, results of phase 3 trials showed a numerical imbalance in the occurrence of second primary malignancies (SPMs) between patients treated with LEN (in combination with melphalan or immediately after high-dose melphalan therapy and stem cell transplantation) and control cohorts. SPMs were analyzed in clinical trials of LEN across indications, including MDS. Methods: This was a single arm analysis of SPM data retrieved from RBC transfusion-dependent patients with IPSS Low- or Int-1-risk MDS with or without del(5q) who received LEN as monotherapy in 5 studies (MDS-001, -002, -003, -004, and -007). The cutoff date was February 28, 2011. SPMs were defined using MedDRA (Medical Dictionary for Regulatory Activities) categories of invasive SPMs (hematologic malignancies and solid tumors) and non-melanoma skin cancers (NMSC). Acute myeloid leukemia (AML) is considered part of the natural history of disease progression in MDS. Although further follow-up is needed, results of a phase 3 study showed no obvious evidence for an increased risk of AML progression in LEN-treated RBC transfusion-dependent patients with IPSS Low- or Int-1-risk MDS and del(5q) (Fenaux P et al. Blood 2011;doi: 10.1182/blood-2011-01-330126). AML was not included in the present analysis. The overall number of SPMs (invasive malignancies and NMSC), and the number and incidence rate (IR) of all invasive SPMs were evaluated, with IR defined as the number of new events per 100 person-years (pys). The IR of invasive SPMs was compared with the IR of new events of invasive cancer as reported from the SEER (Surveillance, Epidemiology, and End Results) cancer registry (2.1/100 pys for persons aged ≥ 65 years) (Howalder N et al. National Cancer Institute, 2011). Results: The combined population of all 5 studies comprised 557 LEN-treated patients. The median age was 71 years (range 27–95 years) and 72% of patients were aged ≥ 65 years. 88 patients (15.8%) had a prior history of cancer including malignant melanoma, meningioma, breast cancer, lung cancer, squamous cell carcinoma, and basal cell carcinoma. A total of 28 patients (5.0%) developed ≥ 1 SPM, including 17 (3.1%) with an invasive SPM and 12 (2.2%) with NMSC; 1 patient had both an invasive malignancy and a NMSC. Two of the 17 patients with invasive SPMs had a B-cell malignancy and 15 had solid tumors of heterogeneous type. Of the 28 patients with SPMs in total, 5 patients had a prior history of cancer. The IR of invasive SPMs was 2.60/100 pys (95% confidence interval 1.56–4.07), which is consistent with the IR reported in the SEER database among patients in this age group (2.1/100 pys for persons aged ≥ 65 years). The median time to onset of SPMs was 13.5 months (range 0.3–48.6 months). Conclusion: There was no clear evidence to associate LEN treatment with an increased risk of developing SPMs in patients with Low- or Int-1-risk MDS with or without del(5q). The IR of invasive SPMs among these LEN-treated patients is what would be expected from population-based estimates of invasive cancer incidence among persons in this age group. The collection of data on SPMs in LEN-treated patients including post-marketing information is ongoing. Disclosures: Giagounidis: Celgene Corporation: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. List:Celgene Corporation: Consultancy, Honoraria, Research Funding. Fenaux:Merck: Honoraria; Johnson & Johnson: Honoraria; Amgen: Honoraria, Research Funding; Roche: Honoraria, Research Funding; Celgene Corporation: Honoraria, Research Funding; Cephalon: Honoraria; Novartis: Honoraria. Benettaib:Celgene Corporation: Employment, Equity Ownership. Brown:Celgene Corporation: Employment, Equity Ownership. Zhong:Celgene Corporation: Employment, Equity Ownership. Brandenburg:Celgene Corporation: Employment, Equity Ownership. Mufti:Celgene Corporation: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

B Cell Lymphoma In Association with Multiple Myeloma: Analysis of the Biologic Relationship

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1590-1590 ◽  
Author(s):  
Anuj K. Mahindra ◽  
Aliyah R. Sohani ◽  
Christiana E. Toomey ◽  
James S. Michaelson ◽  
Jeffrey A. Barnes ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Board Of Directors ◽  
Light Chain ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Prior History ◽  
Advisory Committees ◽  
Age Of Diagnosis ◽  
History Of

Abstract Abstract 1590 Background: The occurrence of a secondary lymphoma in patients with a prior history of B-cell lymphomas has been reported.1, 2 There are few reported occurrences of Multiple Myeloma (MM) in patients (pts) with a prior history of lymphoma and the biologic relationship between the two neoplasms in such cases is unknown. Methods: We queried our IRB approved clinicopathologic database of hematologic malignancies for patients with lymphoma and MM. Of the 4165 pts with B-cell lymphoma and 804 pts with MM, 6 pts with a history of B-cell lymphoma developed MM and 1 patient with a prior history of MM developed a B-cell lymphoma. We describe the morphology, immunophenotype, and clinical features of the 7 pts. The clonal relationship of the 2 components was analyzed using sequencing analysis of immunoglobulin heavy chain variable region (IgVH) genes and by light chain restriction. Results: There were 5 men and 2 women (median age of diagnosis of lymphoma, 65 years; median age of diagnosis of MM, 71 years). The pts with lymphoma included 2 pts with diffuse large B cell lymphoma, 2 pts with small lymphocytic lymphoma, 2 pts with follicular lymphoma and 1 patient with lymphoplasmacytic lymphoma. The development of MM was metachronous in 5 cases, following B-cell lymphoma by 3 years to 23 years and synchronous in 1 case. In 1 patient, the B-cell lymphoma developed 6 years after the diagnosis of MM. 6 pts achieved complete remission after treatment for lymphoma and 1 patient is ongoing treatment. 6 of the 7 pts required treatment for MM soon after diagnosis. 1 patient has smoldering MM and continues to be observed 57 months after diagnosis. FISH analysis indicated IgH rearrangement in 3 pts with MM; 1 patient with 17p deletion and monosomy 13; 3 pts had normal FISH and metaphase cytogenetics. In 3 pts, both neoplasms were kappa light chain restricted; in 1 patient both were lambda restricted; in 1 patient, the lymphoma was lambda light chain restricted while the MM was kappa light chain restricted and the reverse in another pt; in 1 patient the B-cell lymphoma was light chain negative and the MM was kappa restricted. IgVH rearrangement studies in 4 patients in whom tissue samples were available indicated that the two were clonally unrelated in 3 patients and related in only 1 patient. Conclusion: Clonality analysis of rearranged immunoglobulin genes from patients with both B-cell lymphoma and MM provide evidence of separate clonal origins of the two tumors in the majority of cases, thus excluding secondary transformation of the original B-cell clone. The presence or absence of a genetic predisposition to the development of multiple B cell malignancies requires further study.3 Disclosures: Off Label Use: The combination of lenalidomide and everolimue is an off label use in multiple myeloma. Abramson:Genentech: Consultancy; Novartis: Consultancy. Raje:Amgen: Membership on an entity's Board of Directors or advisory committees; Astra Zeneca: Research Funding; Millenium: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Acetylon: Research Funding.

Appropriateness of Thrombophilia Testing in Tertiary Care Centers in Edmonton

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4470-4470
Author(s):  
Alabdurubalnabi Zainab ◽  
Salma Shivji ◽  
Cynthia Wu
Keyword(s):  
Family History ◽  
Board Of Directors ◽  
Protein C ◽  
Protein S ◽  
Test Results ◽  
Advisory Committees ◽  
Increased Risk ◽  
History Of ◽  
Thrombophilia Testing

Abstract INTRODUCTION Thrombophilia is associated with an increased risk of venous thromboembolism (VTE). Despite this link, determining the presence or absence of such conditions has no role in VTE management including determining the choice or duration of anticoagulant therapy. Testing can be potentially harmful when results are misinterpreted or impact patient anxiety and insurance eligibility. METHODS We performed a retrospective chart review of adult patients presenting to the emergency department (ED) or were admitted to the University of Alberta Hospital (UAH), Royal Alexandra Hospital (RAH) and Grey Nuns Hospital (GNH) and underwent any number of thrombophilia tests (including factor V Leiden [FVL], prothrombin gene mutation [PT20210], protein C [PC], protein S [PS], antithrombin [AT] and antiphospholipid antibody testing). To assess for appropriateness of testing, categories of data were collected including presence of other strong risk factors obviating the need to look for other causes, indicators for higher yield (age of patient, presence of family history of VTE, idiopathic nature of VTE), presence of factors that confound testing (such as therapeutic anticoagulation) and relevant follow up (appropriate repeat testing when necessary). We also collected basic patient demographics, VTE details and ordering physician/service details to evaluate under what circumstances testing may be ordered more frequently. RESULTS 134 charts of patients tested for thrombophilia were reviewed between 2007-2013 at UAH and RAH Hospitals. A total of 965 thrombophilia tests were done (see analysis table). 13.4% of the testing was ordered by hematologists, 23.1% by neurologists, 52.2% by other internists. Overall, all patients had tests performed inappropriately, lacked appropriate follow up or had uninterpretable results and none had documented counseling prior to thrombophilia testing. CONCLUSIONS Thrombophilia testing is frequently ordered inappropriately and not adequately followed up. Strategies to educate physicians on indications and limitations of testing are warranted. These strategies can help decrease over/under/misinterpretation of thrombophilia testing as well as result in significant savings to the health care system if testing can be reduced. Table 1. Demographics Sample Size Males Females Total 74 (55.22%) 60 (44.78%) 134 (100%) Age at time of testing (Yrs) Range 19-88 Average 48.7 Patients' Test Results Test Times Performed Abnormal Results APCR 134 (100%) 32 (23.8%) FVL genetic test 58 (43%) 21 (39%) PT20210 105 (77%) 4 (3.8%) Protein C 100 (74.1%) 8 (8%) Protein S 99 (73.3%) 16 (16.2%) AT levels 99 (73.3%) 19 (19.2%) Anticardiolipin Ab 117 (86.7%) 4 (3.4%) Lupus Anticoagulant 109 (81.3%) 10 (10.2%) Provoking Factors Patients with One or More Provoking Factors Major 10 7.4% Moderate 74 56% Minor 29 21.8% No Provoking Factors 49 36.8% Family History of VTE 12 8.9% Protein C and Protein S Testing Done During Acute VTE 64 64% Patient was on Warfarin 25 25% Number of Abnormal Test Results 24 16% Number of Repeated Abnormal Tests 0 0% AT Testing Total Tests Performed 99 73.3% Done During Acute VTE 62 63% Patient was on Therap. Heparin or LMWH 62 62.6% Number of Abnormal Test Results 19 19.2% Abnormal Tests Repeated? 7 37% Repeat Tests Showing Normal Results 3 57% APA Testing Tests were Repeated After 12 Weeks for Confirmation 11% Disclosures Wu: Leo Pharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees.

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

Blood ◽  
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.

scholarly journals Crizanlizumab 5.0 Mg/Kg Exhibits a Favorable Safety Profile in Patients with Sickle Cell Disease: Pooled Data from Two Phase II Studies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 991-991 ◽  
Author(s):  
Julie Kanter ◽  
Darla K Liles ◽  
Kim Smith-Whitley ◽  
Clark Brown ◽  
Abdullah Kutlar ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Board Of Directors ◽  
Sickle Cell ◽  
Research Funding ◽  
Pooled Analysis ◽  
Advisory Committees ◽  
Phase Ii Studies ◽  
Increased Risk ◽  
History Of ◽  
Favorable Safety

Background: Crizanlizumab, a humanized monoclonal antibody that binds P-selectin and blocks interaction with its ligands (including leukocyte PSGL-1), is under investigation for preventing vaso-occlusive crises (VOCs) in individuals with sickle cell disease (SCD). Crizanlizumab 5.0 mg/kg was shown to significantly reduce the median annual rate of VOCs by 45.3% versus placebo (Hodges-Lehmann median absolute difference of -1.01 vs placebo, 95% CI [-2.00, 0.00]; P=0.01) (Ataga et al. N Engl J Med 2017). Aims: This pooled analysis evaluated key safety endpoints in patients treated with the recommended dose of crizanlizumab (5.0 mg/kg monthly, following 2 loading doses in the first month). Methods: Data were pooled from 2 Phase II studies of SCD patients (any genotype) with a history of VOCs leading to a healthcare visit. SUSTAIN (NCT01895361) was a randomized, placebo-controlled study in patients aged 16-65 years who had experienced 2-10 VOCs in the previous 12 months. SOLACE-adults (A2202) is an ongoing, open-label PK/PD study (NCT03264989) in patients aged 16-70 years who had experienced at least 1 VOC in the previous 12 months; data cut-off for this analysis was 1 March 2019. Adverse events (AEs) were evaluated based on MedDRA v21.1. AE severity in SOLACE was assessed based on CTCAE v5; in SUSTAIN, severity was collected as mild/moderate/severe but then recategorized for this analysis to a 5-point scale similar to CTCAE grading. AEs of special interest (ie known class effects; AEs identified preclinically or in previous studies; or potentially relevant based on the mechanism of action of crizanlizumab) were also evaluated and included infections, infusion-related reactions (IRRs) and hemostatic effects. As monoclonal antibodies can induce an immune response, anti-drug antibodies (ADAs) were also measured. Results: In total, 111 patients (SUSTAIN, n=66; SOLACE, n=45) received crizanlizumab 5.0 mg/kg: 59 females (53.2%) and 52 males (46.8%). Median age was 29 years (range 16-65). The most common SCD genotypes were HbSS (n=73; 65.8%) and HbSC (n=19; 17.1%), and 75 patients (67.6%) were receiving hydroxyurea (HU). Most patients (n=67; 60.4%) had 1-4 VOCs in the previous 12 months. Median duration of exposure to crizanlizumab was 46 weeks (range 4-58). At least 1 AE was reported in 94 patients (84.7%), the most common (≥15%) being headache (n=22; 19.8%), nausea (n=18; 16.2%) and back pain (n=17; 15.3%). AEs were mild/moderate (grade 1 or 2) and resolved spontaneously in most patients; 23 patients (20.7%) had a grade 3 AE and 1 (0.9%) had a grade 4 AE (neoplasm). At least 1 serious AE was reported in 24 patients (21.6%); serious AEs with a suspected relationship to crizanlizumab were reported in 6 patients (5.4%). Twenty-eight patients (25.2%) discontinued treatment prematurely (n=23 in SUSTAIN, n=5 to date in SOLACE): discontinuations due to AEs (bradycardia and breast cancer) occurred in 2 patients (1.8%); neither was considered related to crizanlizumab. There were 2 on-treatment deaths in SUSTAIN, but neither were considered related to crizanlizumab. Infection events were reported in 51 patients (45.9%), the most common (≥5%) being upper respiratory tract infection (n=13, 11.7%) and urinary tract infection (n=11, 9.9%). There were no grade 4 infections and none led to discontinuation. Data suggest no increased risk or severity of infection in studies with crizanlizumab. Two patients (1.8%) experienced IRRs; the events were not serious and did not lead to discontinuation. Bleeding events were rare, with most observed hemostatic AEs being abnormal laboratory parameters occurring only once. Treatment-induced ADAs were transiently detected in 1 patient (0.9%) and spontaneously resolved. There were no clinically relevant laboratory (hematology, biochemistry, liver) or ECG abnormalities, or vital sign changes, and no notable differences in the AE incidence rates by gender, ethnicity or HU use. Conclusions: This pooled analysis shows that crizanlizumab 5.0 mg/kg was well tolerated, with a favorable safety profile, in patients with SCD and a history of VOCs. Most AEs were mild/moderate, and discontinuations due to AEs were infrequent. The immunogenic potential of crizanlizumab appears low and there is currently no evidence for an increased risk of infection or bleeding. SOLACE-adults and SOLACE-kids (6 months to &lt;18 years) are ongoing, and the randomized Phase III STAND trial is recruiting. Disclosures Kanter: bluebird bio, Inc.: Consultancy; SCDAA: Membership on an entity's Board of Directors or advisory committees; NHLBI: Membership on an entity's Board of Directors or advisory committees; Rockpointe: Honoraria; Peerview: Honoraria; Jeffries: Consultancy; Medscape: Honoraria; GLG: Consultancy; Cowen: Consultancy; Guidepoint Global: Consultancy; Sangamo: Consultancy, Honoraria; Modus: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Imara: Consultancy. Liles:Novartis: Other: PI on clinical trial Sickle cell ; Shire: Other: PI on clinical trial Sickle cell ; Imara: Other: PI on Clinical trial- Sickle cell . Brown:Novartis, Inc: Research Funding. Kutlar:Bluebird Bio: Other: DSMB Member; Micelle Biopharma: Other: DSMB Chair; Novartis: Consultancy; Global Blood Therapeutics, Inc. (GBT): Research Funding; Novo Nordisk: Research Funding. Elliott:Novartis: Employment, Equity Ownership. Shah:Novartis Pharmaceuticals: Employment, Other: Shareholder. Lincy:NOVARTIS PHARMA AG: Employment. Poggio:Novartis: Employment. Ataga:Advisory Board: Global Blood Therapeutics, Novartis: Membership on an entity's Board of Directors or advisory committees, Other: VINDICO WILL FORWARD DISCLOSURES ONCE RECEIVED AND SIGNED NOT RECEIVED TO DATE; VINDICO WILL FORWARD DISCLOSURES ONCE RECEIVED AND SIGNED NOT RECEIVED TO DATE: Other: VINDICO WILL FORWARD DISCLOSURES ONCE RECEIVED AND SIGNED NOT RECEIVED TO DATE; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Emmaus Life Sciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bioverativ: Honoraria, Membership on an entity's Board of Directors or advisory committees.

scholarly journals Transfusion Requirements in Adult Patients with Paroxysmal Nocturnal Hemoglobinuria with or without a History of Bone Marrow Disorder Receiving Ravulizumab and Eculizumab: Results from a Phase 3 Non-Inferiority Study Extension

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 31-33
Author(s):  
Antonio Risitano ◽  
Jun-Ho Jang ◽  
Lee Gyeong-Won ◽  
Wanchai Wanachiwanawin ◽  
Hubert Schrezenmeier ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Sample Size ◽  
Board Of Directors ◽  
Research Funding ◽  
Paroxysmal Nocturnal Hemoglobinuria ◽  
Complement Inhibitor ◽  
Phase 3 ◽  
Advisory Committees ◽  
Treatment Groups ◽  
History Of

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare and life-threatening hematologic disorder leading to hemolytic anemia, which can occur concomitantly with bone marrow disorders (BMD), such as aplastic anemia (AA) and myelodysplastic syndrome (MDS). Accordingly, patients with PNH often require red blood cell (RBC) transfusions to treat anemia due to hemolysis or bone marrow failure. After demonstrating a non-inferior efficacy and safety profile in two of the largest clinical trials to date, ravulizumab was approved as a treatment for adults with PNH, including patients with an underlying history of bone marrow disease, who are transfusion dependent or independent. Aims: To assess the efficacy of ravulizumab in patients with PNH with or without an underlying pathology of AA or MDS, and to investigate the impact of ravulizumab on transfusion burden as measured by number of transfusions and total packed RBC (pRBC) units transfused over a 52-week period. Methods: This phase 3 multicenter, randomized, active-controlled, open-label study (study 301, NCT02946463) enrolled complement-inhibitor-naïve patients with PNH. Patients were aged ≥ 18 years with a confirmed diagnosis of PNH by flow cytometry and lactate dehydrogenase (LDH) level ≥ 1.5x the upper limit of normal (ULN; 246 U/L). Patients received either ravulizumab or eculizumab for 26 weeks; after which all patients received ravulizumab from week 26 to week 52. Efficacy outcomes included the proportion of patients achieving transfusion avoidance (TA), number of pRBC units transfused and the number of pRBC or whole blood transfusions (WBT) received from baseline to 26 and 52 weeks of treatment. In this retrospective analysis, outcomes were analysed for the following subgroups: AA, MDS or no BMD (medical history of AA or MDS was determined by the investigator at screening). Descriptive statistics were calculated for continuous (means) and categorical variables (numbers and percentages). Formal hypothesis testing for significance between treatment groups was not performed. Results: Of the 246 patients included in the study, 79 had a history of AA (32.1%) and 13 (5.3%) had a history of MDS. Baseline characteristics were comparable between treatment groups. From baseline to week 26, a comparable proportion of patients with AA achieved TA to those with no BMD; 75.6% for patients with AA and no BMD receiving ravulizumab, and 60.5% and 73.7% for patients with AA and no BMD receiving eculizumab, respectively (Table 1). Importantly, TA was maintained through 52 weeks, with similar proportions of patients with AA (87.1‒91.3%) maintaining TA to patients without BMD (85.7‒91.5%). More specifically, 65.9% of patients with AA and 69.2% of patients without BMD achieved TA through 52 weeks of ravulizumab treatment, and 55.3% and 63.2% of patients with AA and without BMD, respectively, achieved TA on eculizumab followed by ravulizumab. The proportion of patients with MDS who achieved TA appeared numerically lower compared with patients with AA or no BMD, however, this subgroup sample size was small. Furthermore, a lower proportion of patients on ravulizumab with AA or MDS received any transfusion from baseline to weeks 26 and 52 compared with those treated with eculizumab followed by ravulizumab: for week 26, 24.4% and 57.1% for ravulizumab versus 39.5% and 100.0% for eculizumab in patients with AA and MDS, respectively, and for week 52, 29.3% and 57.1% for patients with AA and MDS receiving ravulizumab for 52 weeks versus 44.7% and 100.0% for patients with AA and MDS treated with eculizumab followed by ravulizumab. In addition, ravulizumab-treated patients with AA or MDS had numerally fewer transfusions and units of pRBC/WBT compared with those who received eculizumab followed by ravulizumab. Overall, the exploratory nature of the analysis and small sample size means that interpretation of the data is limited. Conclusions: This analysis demonstrates that majority of patients with PNH and AA who received ravulizumab avoided the need for transfusion up to 52 weeks of treatment. Patients treated with ravulizumab for the 52-week period had numerically fewer transfusions and units of pRBC/WBT transfused compared with patients who received eculizumab followed by ravulizumab. Overall, these findings support the use of ravulizumab in complement-inhibitor-naïve patients with PNH, with or without a history of BMD. Disclosures Risitano: Amyndas: Consultancy; Samsung: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Jazz: Speakers Bureau; RA pharma: Research Funding; Pfizer: Speakers Bureau; Apellis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Biocryst: Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Alnylam: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Achillion: Membership on an entity's Board of Directors or advisory committees. Schrezenmeier:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Yonemura:Alexion Pharmaceuticals: Honoraria, Research Funding. Munir:Alexion: Honoraria; F. Hoffmann-La Roche: Consultancy, Other: Medical writing support, furnished by Scott Battle, PhD, of Health Interactions, was funded by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Pavani:Alexion Pharmaceuticals: Current Employment. Wang:Alexion Pharmaceuticals Inc.: Current Employment. Kulagin:Alexion Pharmaceuticals Inc.: Consultancy, Research Funding. Kulasekararaj:Alexion Pharmaceuticals Inc.: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sicre de Fontbrune:Alexion Pharmaceuticals Inc.: Honoraria, Research Funding. Röth:Novartis: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria; Biocryst: Consultancy, Honoraria; Apellis: Consultancy, Honoraria; Alexion Pharmaceuticals Inc.: Consultancy, Honoraria, Research Funding.

scholarly journals Impact of Race/Ethnicity on Cancer Associated Thrombosis Among Underserved Patients with Cancer

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 176-176
Author(s):  
Wilson L Da Costa ◽  
Danielle Guffey ◽  
Raka Bandyo ◽  
Courtney D Wallace ◽  
Carolina Granada ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Safety Net ◽  
Incidence Rates ◽  
Advisory Committees ◽  
Vein Thrombosis ◽  
Patients With Cancer ◽  
History Of ◽  
Cancer Types ◽  
Race Ethnicity ◽  
Cancer Associated Thrombosis

Abstract Introduction: Cancer-associated thrombosis (CAT) is common among patients with cancer. Risk factors for CAT include type of malignancy, advanced stage, and chemotherapy treatment, but the association of CAT with race and ethnicity remains controversial. Identifying the incidence of CAT among populations susceptible to inequalities in healthcare delivery may help delineate preventive strategies. Methods: We performed a retrospective cohort study at Harris Health System (HHS), a safety-net healthcare system that provides care for underserved minorities and uninsured patients in Houston, TX. We created an integrated database that linked consecutive patients with newly diagnosed invasive cancer with structured electronic health record (EHR) data from 2011-2020 (Figure 1). We followed patients from time of cancer diagnosis to time of first VTE, death, or loss of follow-up. VTE was defined as radiologically confirmed pulmonary embolism (PE), lower extremity deep vein thrombosis (LE-DVT), catheter-related DVT (CR-DVT), or splanchnic vein thrombosis in either inpatient or outpatient setting. We used VTE ICD9/ICD10 billing codes to assess for potential events and confirmed incident, recurrent, and historical events through medical record review. VTE occurring within 30 days prior to cancer diagnosis were considered as CAT at diagnosis. Incidence rates were assessed per 100 person-year (py) within 1 year of diagnosis and stratified by race/ethnicity, cancer type, and cancer stage. Cumulative incidence of VTE was assessed through competing risk method with death as the competing cause. Multivariable Fine-Gray competing risk models were performed to determine the effect of race/ethnicity on the risk of CAT, adjusted for age, sex, body mass index, insurance, cancer site, stage, systemic therapy, recent hospitalization, and prior history of VTE. Results: A total of 9,353 cancer patients were included in the study, where 49.3% were Hispanics, 27.6% were Non-Hispanic Blacks (NHB), 15.5% were Non-Hispanic Whites (NHW), and 7.6% were Asian/Pacific Islander (PI). Most patients (74.7%) were uninsured, 35.8% were obese, 19% had recent hospitalization, and 31.9% had stage IV disease. Overall, 832 developed CAT within 1 year, including 49.4% PE, 28.1% LE-DVT, and 17.1% CR-DVT. The median onset was 69 days (IQR 20-154), but a significant proportion (n=92) was diagnosed in the month before diagnosis. The incidence of CAT was 7.3% at 6 months and 9.6% at 1 year. The overall incidence rate was 11/100 py with a similar trend from 2011 to 2020. Figure 2 shows the variation in incidence rates for different cancer types across stages. The rate increased 2- to 10-fold from stage I to IV, reaching &gt;40/100 py among patients with pancreatic and upper gastrointestinal cancers. Figure 3 shows the impact of race/ethnicity on the incidence of CAT, with 9.3% and 8.4% for NHW and NHB at 6 months, compared to 6.5% and 3.8% for Hispanics and Asian/PI, respectively. In the adjusted multivariable analysis, the risk of CAT remained lower in Hispanics vs. NHW (SHR 0.80 [0.65-0.97]) and Asian/PI vs. NHW (SHR 0.48 [0.32-0.73]). There was no difference in NHB vs. NHW (SHR 1.04 [0.84-1.27]). Other important covariates included history of VTE (SHR 2.29 [1.32-3.97]) and prolonged hospitalization (SHR 1.53 [CI 1.31-1.80]) in addition to staging and cancer types. Compared to no systemic therapy or adjuvant endocrine only, there was a higher incidence of VTE in patients receiving chemotherapy (SHR 1.72 [1.39-2.15]), targeted therapy (SHR 1.58 [1.12-2.23]), immunotherapy (SHR 2.13 [1.30-3.48], but not non-adjuvant endocrine therapy (SHR 0.91 [0.40-2.08]). Conclusion: In the current cancer registry-linked EHR cohort with a high proportion of Hispanics and Blacks from a large safety-net healthcare system in the US, we have observed a high incidence rate of CAT at 11/100 py. This rate is much higher than 3.9-5.8/100 py reported in contemporary cancer registries in Europe (PMID 27709226, 33171494), and likely reflects advanced disease and comorbidity at the time of diagnosis due to delayed care from the lack of health insurance. Despite adjusting for patient-, cancer-, and treatment-specific confounders, we found that Hispanics and Asian/PI had ~20% and ~50% lower rate of VTE, respectively, compared to NHW or NHB. This racial/ethnicity difference should be considered in future risk assessment models for CAT. Figure 1 Figure 1. Disclosures Carrier: Sanofi Aventis: Honoraria, Membership on an entity's Board of Directors or advisory committees; LEO Pharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aspen: Membership on an entity's Board of Directors or advisory committees; Boehringer Ingelheim: Honoraria; Servier: Honoraria.

scholarly journals Real-World Observations and Practical Considerations of Subcutaneous Daratumumab Administration in Multiple Myeloma

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 5018-5018
Author(s):  
E. Bridget Kim ◽  
Elizabeth O'Donnell ◽  
Andrew R. Branagan ◽  
Jill N. Burke ◽  
Cynthia C. Harrington ◽  
...  
Keyword(s):  
High Risk ◽  
Board Of Directors ◽  
Comparable Efficacy ◽  
Prior History ◽  
Rapid Infusion ◽  
Advisory Committees ◽  
Optimal Monitoring ◽  
Systemic Reactions ◽  
Patient Reported ◽  
History Of

Abstract Background: Subcutaneous daratumumab (dara-SC) has several advantages over intravenous daratumumab (dara-IV). It has significantly shorter administration time, lower rates of systemic reactions, and smaller administration volume, while maintaining comparable efficacy and safety. Its fixed dosing allows for easier preparation. At our institution, standard approach is to monitor for 4h following the initial dara-SC dose for those at high risk for systemic reactions, defined as no prior dara use, treatment break ≥90d, or any prior history of reactions. We also administer montelukast and fexofenadine for the first 2 doses of dara-SC in addition to the usual standard pre-medications. Herein, we share our experience with dara-SC use in both dara-naïve and dara-exposed patients in order to gain practical insight, such as optimal monitoring duration, considerations for transitioning between dara-IV and dara-SC, and the place of therapy for dara-IV based on adverse events (AEs). Methods: Between June 2020 and June 2021, patients who received at least one dose of dara-SC were identified and their record was reviewed for any systemic reactions, hypersensitivity medication use, and patient reported AEs. Results: Since June 2020, our dara-SC drug use increased from 38% to 91% of all doses. There were 208 patients who received at least 1 dose of dara-SC. Of 208 patients, 99 (47.6%) were dara-naïve and 109 (52.4%) had prior dara exposure - either transitioning from dara-IV on schedule or had dara-IV as a past line of therapy. We identified 124 patients who met the criteria for 4h post dara-SC injection monitoring: dara-naïve (79.8%), treatment break ≥90d (18.5%), or prior history of reactions (1.6%). Only 5 experienced systemic reactions, representing 4% among those at high risk. All reactions were mild requiring minimal intervention and occurred following the first dara-SC dose. Onset of reactions and type of intervention during the 4h monitoring window were: hypotension (2h; fluid), nausea/vomiting (2.5h; hypersensitivity medications), and sinus tachycardia (4h), while 2 patients had transient chest pressure/tightness at home (1 within 24h, 1 between 1-6d following the dose). Eleven patients (5%) receiving dara-SC converted back to dara-IV, with AEs being the most common reason. Diarrhea, fatigue, and injection site reactions were among the most frequent patient-reported AEs. When transitioning back to dara-IV, a 90min rapid infusion rate was used if &gt;4 prior dara doses were given. No infusion-related reactions were observed. Conclusion: The introduction of dara-SC has significantly improved patient experience. We observed a lower rate of systemic reactions compared to previous reports of 10% with first dose of dara-SC. This may be partly due to our strengthened pre-medication strategy. Opportunities exist to further improve and apply practical considerations when administering dara-SC. Based on our results, shortening on-site monitoring time may be feasible. Disclosures O'Donnell: Onocopeptide: Consultancy; Karyopharm: Consultancy; Janssen: Consultancy; Bristol Myer Squibb: Consultancy; Adaptive: Consultancy; Takeda: Consultancy. Branagan: Adaptive: Consultancy; Sanofi-Genzyme: Consultancy, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy. Raje: Celgene, Amgen, Bluebird Bio, Janssen, Caribou, and BMS: Other. Yee: GSK: Consultancy; Janssen: Consultancy; Amgen: Consultancy; Bristol Myers Squibb: Consultancy; Adaptive: Consultancy; Oncopeptides: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; Karyopharm: Consultancy.

Provider Practices Regarding Prophylactic Anticoagulation in Children with Leukemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3412-3412
Author(s):  
Nicole Kucine ◽  
Melanie Degliuomini ◽  
Elizabeth Mauer ◽  
Victoria Cooley ◽  
Linda M Gerber ◽  
...  
Keyword(s):  
Risk Factors ◽  
Board Of Directors ◽  
Response Rate ◽  
Primary Prophylaxis ◽  
Central Line ◽  
Secondary Prophylaxis ◽  
Advisory Committees ◽  
Pediatric Leukemia ◽  
Vte Prophylaxis ◽  
Anticoagulant Prophylaxis

Venous thromboembolism (VTE) is a known complication in children with leukemia, with prevalence in acute lymphoblastic leukemia (ALL) reported as high as 37% (Mitchell, et al, Cancer, 2003). Indwelling catheters, hyperviscosity, mediastinal masses, and medications such as asparaginase, can all contribute to increased VTE risk. In addition to national interest in preventing VTE in hospitalized children, decreasing risk of VTE in children with cancer is of great importance to pediatric hematologist/oncologists. The International Society of Hemostasis and Thrombosis released a guidance statement (Tullius, et al, JTH, 2017) that suggested considering thromboprophylaxis on a case-by-case basis for children with cancer and multiple VTE risk factors, and suggested discontinuing anticoagulant prophylaxis when predisposing conditions resolve. Children with leukemia certainly may have multiple risk factors and therefore deserve consideration for prophylaxis. The Children's Oncology Group is currently conducting a clinical trial studying thromboprophylaxis during induction for ALL. Given the importance of reducing VTE and the interest in thromboprophylaxis, we sought to assess practitioners' practices regarding thromboprophylaxis in children with leukemia. We performed a cross sectional, anonymous survey of pediatric members of VENUS (the VTE Network of the Hemostasis and Thrombosis Research Society) and ASH (the American Society of Hematology) using Qualtrics, a secure online survey tool. Responses were excluded if physicians answered no to either of 2 screening questions (related to clinical practice and board certification/eligibility), or if no questions were answered after screening. A gift card incentive was offered anonymously. Institutional IRBs approved this study. 870 surveys were distributed, with a response rate of 17.7%; after exclusions, a total of 142 surveys were included. Demographics were well balanced regarding size of program and years in practice. When asked about which anticoagulant agents may be used for thromboprophylaxis (n=36), 92% of those responding reported using enoxaparin (Table 1). In addition, 36% use Apixaban and 14% use Rivaroxaban. When asked if they ever provide primary VTE prophylaxis to children with leukemia (n=127), 71% said no, while 29% answered yes (Table 1). When asked in what scenarios primary prophylaxis was used, the most common answer was in leukemia patients with a known inherited thrombophilia (57%). Also common were children with mediastinal masses with vessel compression, and children enrolled on the COG prophylaxis study. Some additional scenarios offered were AYA patients, and those with additional risk factors, such as obesity and immobility. When asked about duration of primary prophylaxis (n=36), the most common times for discontinuing therapy were resolution of mediastinal mass and/or vessel compression (58%), end of all asparaginase therapy (50%), and until the central line is removed (42%). A smaller number of physicians (22%) would consider continuing anticoagulant prophylaxis until the end of all cancer chemotherapy. When questioned about secondary prophylaxis following VTE (n=127), 8% of respondents never provide post-VTE prophylaxis, 11% always give post-VTE prophylaxis, and 81% used post-VTE prophylaxis in certain cases (Table 1.) The most common stopping point for secondary prophylaxis (n=116) was after central line removal (55%), followed by completion of all asparaginase therapy (41%). Our study is limited by a low response rate. Due to technical issues, we had missing data for many questions and could not obtain free-text answers for some of the prophylaxis questions, limiting full data acquisition. Despite these issues, our results provide some insights into current practices of pediatric hematologist/oncologists. This study shows that many physicians are not utilizing primary anticoagulant prophylaxis in their pediatric leukemia patients, despite the high-risk nature of these patients, possibly trying to balance bleeding risk due to thrombocytopenia. Duration of anticoagulant therapy varies, and it is likely that there are no clear definitions regarding resolution of predisposing factors. Given their unique set of risk factors, and the potential morbidity associated with VTE, further study of VTE prophylaxis is essential for development of pediatric leukemia-specific guidelines. Disclosures Cooley: off-label: Other: drug use. Acharya:Bayer Pharmaceuticals, LLC: Research Funding; Novonordisk: Membership on an entity's Board of Directors or advisory committees; BioProducts Laboratory: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: We surveyed physicians on which anticoagulants they use in their pediatric leukemia patients and the majority of drugs offered as answer choices are technically off-label.

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