Kooperativer Bibliotheksverbund

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 3050-3050

Abstract: Background: Pregnant or breastfeeding women are routinely excluded from clinical trials due to fear of teratogenicity and toxicity of therapeutic agents, despite a paucity of evidence to support this practice. In response to the diethylstilbesterol (DES) and thalidomide-induced embryopathy in the mid-20 th century, the US Food and Drug Administration (FDA) released new regulations excluding Women of Child-Bearing Potential (WoCBP) from phase I and II trial participation, followed by an introduction of a new pregnancy category labelling system in 1979. The legacy of these measures is a reliance on accidental exposure pregnancy data rather than rigorous clinical trial efficacy and safety data for medication use in pregnancy and lactation. WoCBP when enrolled in clinical trials are often subjected to prescriptive contraceptive requirements to mitigate the risk of accidental pregnancy, without informed consent for the contraceptive side effects. These barriers to trial participation for WoCBP, particularly in the setting of life-threatening haematological diseases, prevent timely access to therapies only accessible via clinical trial participation. Lymphoma and leukaemia in pregnancy occur with an approximate incidence of 1 in 6000 and 1 in 75,000-100,000 pregnancies respectively. We examined the rates and rationale for exclusion of these patients from clinical trials, as well as contraceptive requirements for WoCBP. Methods: We conducted a cross-sectional observational study of clinical trial protocols recruiting patients with potentially life-threatening haematological malignancies. We searched the clinicaltrials.gov clinical trials database for trial protocols enrolling acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), Hodgkin lymphoma (HL) and/or Diffuse Large B Cell lymphoma (DLBCL) between January 2016 and January 2021. Studies were included if they included WoCBP (15-55 years of age). Studies without complete electronic protocol access were excluded. The following data was collected: target disease, study phase, study location, age of patients, whether pregnant or lactating women were excluded (rationale if provided including evidence of teratogenicity), type of contraception and duration mandated and presence or absence of informed consent for contraception. Results: We identified 68 trials for AML, ALL, DLBCL and HL (40%, 26%, 21% and 13% respectively) (Table 1). Most were phase I-II studies (91%) of novel agents (90%) and of note, the majority were of non-chemotherapy agents (83%). The majority (97%) excluded pregnant women and (69%) without providing rationale. Only 2% cited evidence for embryopathy in either human or animal studies. Most studies (84%) explicitly excluded lactating women, of which 85% did not provide justification. Contraception was mandatory in 90% of the protocols, with 47% of these requiring at least two different forms of contraception for the entire study period. These included hormone-based contraception, barrier methods and abstinence. None of the protocols provided informed consent for the potential side effects of the mandated contraceptive methods in the context of the study. Conclusion: The theoretical harm from anti-cancer therapy to the foetus is typically given greater moral precedence than is a pregnant woman's autonomy. Pregnant and lactating women were almost universally excluded from the trials in this study with limited rationale provided. Study protocols frequently mandated contraception without informed consent of its associated risks in the context of the study. This perpetuates the lack of efficacy and safety data in this patient population, and drives a cycle of systematic exclusion, data shortage, and inequity. Pregnant and lactating women with life threatening haematological malignancies with no alternative treatment options should be eligible for clinical trials where this offers potentially life-saving therapy, with appropriate informed consent around the indefinable and potentially harmful effects on their foetus. We propose obligatory rationale for exclusion of pregnant and breastfeeding women in all clinical trials, using safety data from either human or animal studies and contraception informed consent. Figure 1 Figure 1. Disclosures Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-149354

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4940-4940

Abstract: Background: Chemotherapy is potentially harmful to the developing foetus and there is limited data on the foetal impact of immunotherapy except for rituximab. Therefore determining pregnancy status prior to initiation of chemo- and or immuno-therapy (CIT) should be standard of care. Repeat screening or testing during and after chemotherapy should be considered as women often cannot tell that they are pregnant due to overlapping symptoms of pregnancy, malignancy and treatment. This is of particular importance in women who are not on effective forms of contraception for personal choice or clinical reasons. Clinicians cannot presume that a patient's pregnancy status has been checked, or rely on any assumptions of abstinence, contraception or infertility based on secondary amenorrhoea. While CIT teratogenicity should be part of the informed consent discussion and it is recommended that pregnancy screening occur prior to CIT, there are no specific guidelines on this or on testing during CIT. It is our institutional standard to document consent using a standard tick box form to confirm a discussion of common and uncommon side effects of treatment, long term and life threating complications and impacts on fertility. Teratogenicity, pregnancy implications or contraception are not specified. We performed a retrospective review to evaluate the uptake of pregnancy screening prior to and during first-line CIT as well as an audit of documentation of contraception counselling in haematological and solid-organ malignancies at a large Australian tertiary cancer centre. Methods: We searched our electronic outpatient medical record database for Women of Child Bearing Potential (WoCBP) who were diagnosed with a malignancy and received outpatient based CIT between May 1 2015 and June 12 2020. WoCBP was defined as women 18-55 years of age with no record of menopause or definitive infertility. We captured patient demographics, disease details and CIT regimen. We collected result of any serum or urine b-HCG pregnancy tests done within 90 days prior to or during CIT administration and if positive, the pregnancy outcome. We captured any documentation regarding contraception prior to or during treatment. Results: A total of 415 WoCBP with a median age of 42 years (range 19-51) were included. The majority of women (79.3%) were treated for solid organ malignancies compared to haematological malignancies (20.7%) (Table 1). Only 17.1% were screened for pregnancy prior to its initiation. The average time between screening and CIT initiation was 19.5 days (range 0-90 days). Given the broad range of regimens and taking into consideration teratogenicity potential, CIT was categorised as immunotherapy alone (32.5%), chemotherapy containing an alkylating agent (25.8%) or an antimetabolite (3.9%), combination chemoimmunotherapy (15.2%) and other (22.7%). Rates of pregnancy screening within these categories is represented in Figure 1. One patient with early breast cancer had a positive pregnancy test during her 4 th cycle of adjuvant chemotherapy with paclitaxel, in the emergency department for a presentation of nausea, anorexia, abdominal pain and diarrhoea. The outcome in this case was an early spontaneous miscarriage estimated at 3-4 weeks gestation. This is the only patient who had a pregnancy test beyond the first cycle of CIT. Only 14.8% of patients had documentation of past or present contraception methods. None of the patients had documentation regarding counselling on recommended forms of contraception. Conclusion: A minority of WoCBP received a pregnancy test prior to commencing CIT for haematological or solid organ malignancy, and none intentionally received a test prior to subsequent chemotherapy cycles through the oncology/haematology service. Also none of the women had documented counselling on contraception. These results are concerning because missing a positive pregnancy test puts women at risk of foetal complications, accidental miscarriage, potential bleeding risks and avoidable psychosocial stress. Our results are consistent with the 2 other reports on this topic and are likely generalizable to other cancer centres. This highlights the urgent need for guidelines to increase the rate of pregnancy testing in WoCBP receiving CIT and contraception counselling prior to CIT. Figure 1 Figure 1. Disclosures Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-154028

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

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detail.hit.zdb_id: 80069-7

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 11-12

Abstract: Background: Upfront autologous stem cell transplantation (ASCT) in multiple myeloma (MM) following induction therapy has been demonstrated to improve progression free survival (PFS) and overall survival (OS). Consideration of transplant eligibility involves assessment of age (typically & lt;70 years), co-morbidities and frailty. In Australia and New Zealand, approximately 70% of all MM patients aged & lt;70 years undergo upfront ASCT compared to approximately 6% aged 70-75 years (Bergin, MRDR Data). We aimed to review the patterns of transplantation in Australia and New Zealand in patients ≥70 years of age and examine survival outcomes and predictors of survival in this cohort. Methods: We analysed 8786 MM patients who received ASCT in Australia and New Zealand between 2001 and 2019. 630 (7.2%) were ≥70 years of age. As there was missing data in the registry, additional data was obtained for 466 ≥70 years of age from 20 sites (performance status (PS), melphalan dose and creatinine clearance (CrCl)). These sites were selected on the basis of number of eligible patients in the registry. Kaplan-Meier analysis was performed to determine PFS and OS. Univariate and multi-variate analysis was performed using Cox proportional hazard model to determine predictors of OS. Results: The baseline patient and disease characteristics are presented in Table 1. The total number of ASCT procedures performed for MM has increased over the study period, and the proportion of ASCT patients ≥70 years has also increased from 5% in 2000-2004 to 11% in 2015-2019 (Figure 1). 33% of patients ≥70 years of age received reduced dose melphalan (140mg/m2 versus 200mg/m2) compared with 10% of patients & lt; 70. Poor PS (ECOG & gt; 1/Karnofsky Performance Score & lt; 80) and CrCl did not significantly predict dose reduction of melphalan. At a median follow-up of 3.8 years, median PFS was 3.3 years (95% CI 2.9-3.8) for those aged ≥70 and 3.4 years (95% CI 3.2-3.6) for those 60-69 (P =0.7). Median OS in those aged ≥70 was 5.6 years (95% CI 4.9-6.3) compared to 6.2 years in those 60-69 (5.8-6.6 years) (P = 0.01). There was no difference in median time to platelet and neutrophil engraftment in patients aged ≥ 70 compared to those & lt; 70. There was no significant difference in transplant related mortality at day 100 in those ≥70 years (1.8%, 95% CI 1-3%) compared to those & lt; 70 (1%, 95% CI 0.7-1.2%) (P = 0.07). OS in all patients aged ≥ 70 (n = 630) was significantly better in patients transplanted between 2010-2019 (n = 451) compared to 2000-2009 (n = 179) (HR 1.62, 1.20-2.19, P = 0.002) (Figure 2) likely correlating with access to bortezomib based induction in 2011/2012 in Australia and New Zealand, and is reflected by an increased proportion of patients achieving a partial response (PR) or better at time of ASCT (Table 1). Increased access to novel agents in the relapsed/refractory MM patients as well as improvements in supportive care also may have contributed. On univariate analysis, other predictors of OS in older patients were poor PS (HR 2.44, 95% CI 1.23-4.81, P = 0.01), higher risk disease (Stage III using Durie-Salmon, ISS or R-ISS) (HR 1.42, 95% CI 1.01-2.00, P & lt; 0.042) and failure to achieve a PR prior to ASCT (HR 1.71, 95% CI 1.01-2.87, P = 0.05). On univariate analysis, melphalan dose did not predict OS (HR 1.35, 95% CI 0.89-2.05, P = 0.2). Multivariate analysis of determinants of OS was performed for the patients in whom we obtained the additional data. Because of missing data for both PS and stage, multivariate analysis incorporating all variables of interest (decade of transplant, melphalan dose, disease status at transplant, CrCl, PS and stage at diagnosis) could only be performed in a subset of patients (n = 163) (Table 2). In this cohort the only significant predictor of OS was poor PS (Table 2). Conclusion: There is increasing utilisation of upfront ASCT in patients aged ≥ 70 in Australia and New Zealand. OS in this group of patients has significantly improved over the study period in keeping with access to bortezomib based induction and novel agents in the relapsed and refractory setting. In a highly selected group of patients ≥70 years of age, ASCT is feasible and associated with excellent PFS and OS. On multivariate analysis, PS was the only predictor of OS. The prospective use of established co-morbidity and frailty scores in assessing transplant eligibility in older patients warrants further evaluation. Disclosures Harrison: Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Honoraria; Haemalogix: Consultancy; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CRISPR Therapeutics: Consultancy, Honoraria; F. Hoffmann-La Roche: Consultancy, Honoraria; Janssen: Honoraria; Novartis: Consultancy, Honoraria, Patents & Royalties: wrt panobinostat; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Spencer:AbbVie, Amgen, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Honoraria; Celgene, Janssen and Takeda: Speakers Bureau; AbbVie, Celgene, Haemalogix, Janssen, Sanofi, SecuraBio, Specialised Therapeutics Australia, Servier and Takeda: Consultancy; Amgen, Celgene, Haemalogix, Janssen, Servier and Takeda: Research Funding. Mills:Celgene: Honoraria; Novartis: Honoraria, Other: Meeting sponsorship; AstraZeneca: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees. Hertzberg:Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Support of parent study and funding of editorial support; MSD: Membership on an entity's Board of Directors or advisory committees; Gilead: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Abbvie: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Sidiqi:Amgen: Honoraria; Janssen: Honoraria; Celgene: Honoraria, Other: Travel grant. Kalff:Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria; CSL: Honoraria; Roche: Honoraria. Hamad:Novartis: Honoraria; Abbvie: Honoraria.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-138991

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

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detail.hit.zdb_id: 80069-7

In: Journal of Hematology & Oncology, Springer Science and Business Media LLC, Vol. 9, No. 1 ( 2016-12)

Type of Medium: Online Resource

ISSN: 1756-8722

URL: Article

DOI: 10.1186/s13045-016-0278-x

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2016

detail.hit.zdb_id: 2429631-4

In: Blood, American Society of Hematology, Vol. 138, No. Supplement 1 ( 2021-11-05), p. 4757-4757

Abstract: Introduction Serious infection is common in patients with multiple myeloma (MM), and associated with major morbidity and mortality. Immunoglobulin (Ig) replacement is frequently used to reduce frequency and severity of infections, however evidence is based on small trials conducted & gt;20 years ago. Ig utilisation and associated costs in this patient cohort are rising worldwide. In Australia (Aus), Ig for secondary hypogammaglobulinaemia is funded if total IgG is below lower limit of reference range with a history of recurrent or severe bacterial infection, or in severe hypogammaglobulinaemia (IgG & lt; 4 g/L excluding paraprotein). In New Zealand (NZ), patients generally require a history of recurrent infections and trial of oral antibiotics before commencing Ig. This study aims to outline Ig use in the "real-world" MM setting, identify variation in and predictors of use, and describe association of Ig with survival outcomes. Methods Retrospective review of patients registered on the MRDR, a prospective registry established in 2012, currently open at & gt;60 sites across Aus/NZ. Patients with a diagnosis of MM or plasma cell leukaemia with verifiable data regarding Ig use were included in this analysis. Ig use was confirmed using medical/laboratory records, national Aus Ig dispensing tool or the NZ Blood Service portal. Quality of survival outcomes and cause of death data was augmented via linkage with national death registries. Baseline patient/disease characteristics, therapy and survival outcomes were compared between patients who received any Ig within 24 months of MM diagnosis and non-recipients using chi-square tests for categorical variables and rank sum tests for continuous variables. Variation in Ig use across sites were compared. Kaplan-Meier survival analysis was used to estimate time to Ig and duration of use. A time-dependent Cox analysis was used to compare survival for patients whilst on and off Ig therapy. All statistical analysis was completed on STATA/IC statistical software v16.1 (College Station, TX, USA). Results As of July 2021, & gt;4600 patients with plasma cell dyscrasias are registered on the MRDR. Of these, 2025 patients from 13 sites (12 Aus across five states/territories and one NZ) with verifiable data on Ig were included. 242 (12.0%) received Ig during follow-up, with a median time from MM diagnosis to Ig use of 14.2 months, median duration of Ig use of 54.9 months, and median patient follow-up time of 23 months (Figure 1). At 24 months following MM diagnosis, 14.9% (160 of 1075 patients reaching 24-month follow up) received Ig, and a further 7.6% (82 patients) received Ig later, after 24 months. Administration of Ig within 24 months post-MM diagnosis varied widely across Aus states and territories (2.7%-29.6%), and was 2.0% from one NZ site. Patients administered Ig within 24 months post-MM diagnosis had lower baseline IgG (3.7 vs. 5.6 g/L, p & lt;0.001), IgA (0.3 vs. 0.5 g/L, p=0.027), IgM (0.20 vs. 0.21 g/L, p=0.019) and total serum Ig levels (28.0 vs 56.0 g/L, p & lt;0.001), were more likely to have abnormal Fluorescence in situ hybridization (FISH) results (83.5% vs. 62.7%, p & lt;0.001) and receive immunomodulatory drugs (IMiDs) (28% vs. 12.3%, p & lt;0.001) or anti-CD38 therapy (4.5% vs. 1.2%, p=0.004) first-line compared with patients not administered Ig (Tables 1, 2). Ig use was not associated with an overall survival benefit (HR=0.79, 0.50-1.24, p=0.3). At time of last follow-up, there were 577 deaths (28.5%). Available data on cause of death was available for 175 deaths (30.3%). Of these, 65 deaths (37.1%) had infection listed as primary/secondary cause of death (COD). 64 of 65 infection-related deaths occurred in non-Ig recipients. In patients who received Ig (at any time), 12.5% had infection as primary/secondary COD, compared to 38.5% in non-recipients (p=0.14). Conclusion This Aus/NZ analysis found that 14.9% of MM patients received Ig by 24 months post-MM diagnosis with wide variation in practice. Ig use was associated with lower baseline Ig levels (all subtypes), abnormal FISH and first-line IMiD/anti-CD38 therapy. In this "real-world" cohort, Ig use was not associated with survival, highlighting the need for well-designed contemporary studies to inform evidence-based patient selection, especially with increasing use of Ig and targeted anti-myeloma therapies, and a high burden of infection-related mortality. Figure 1 Figure 1. Disclosures Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Harrison: Haemalogix: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche/Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene/ Juno/ BMS: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Eusa: Consultancy, Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Terumo BCT: Consultancy, Honoraria. Mollee: Janssen, Pfizer: Research Funding; Amgen, BMS, Janssen, Caelum, EUSA, Pfizer, SkylineDx, Takeda: Membership on an entity's Board of Directors or advisory committees, Other: No personal fees received. Quach: GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Antengene: Consultancy, Membership on an entity's Board of Directors or advisory committees; CSL: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen/Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Spencer: Celgene: Honoraria, Research Funding, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria, Research Funding; Bristol Myers Squibb: Research Funding; Takeda: Honoraria, Research Funding, Speakers Bureau; STA: Honoraria. Wood: Amgen, Celgene, Gilead, Janssen, Novartis, Sanofi, Takeda: Research Funding; Abbvie, Amgen, Antengene, Bristol-Myers Squibb, Celgene, Gilead, GSK, Janssen, Novartis, Sanofi, and Takeda.: Other: The Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) has received funding from Abbvie, Amgen, Antengene, Bristol-Myers Squibb, Celgene, Gilead, GSK, Janssen, Novartis, Sanofi, and Takeda. . McQuilten: Amgen, Celgene, Gilead, Janssen, Novartis, Sanofi, Takeda: Research Funding; Abbvie, Amgen, Antengene, Bristol-Myers Squibb, Celgene, Gilead, GSK, Janssen, Novartis, Sanofi, and Takeda.: Other: The Australian and New Zealand Myeloma and Related Diseases Registry (MRDR) has received funding from Abbvie, Amgen, Antengene, Bristol-Myers Squibb, Celgene, Gilead, GSK, Janssen, Novartis, Sanofi, and Takeda. .

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2021-147622

Language: English

Publisher: American Society of Hematology

Publication Date: 2021

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7

In: British Journal of Haematology, Wiley, Vol. 199, No. 2 ( 2022-10), p. 190-204

Abstract: For patients with newly diagnosed multiple myeloma, survival outcomes continue to improve significantly: however, nearly all patients will relapse following induction treatment. Optimisation of induction therapy is essential to provide longer term disease control and the current standard of care for most patients incorporates an immunomodulatory agent and proteasome inhibitor, most commonly lenalidomide and bortezomib in combination with dexamethasone (RVD), with maintenance until progression. Historically there has been limited access to RVD as an induction strategy outside of the United States; fortunately, there is now increasing access worldwide. This review discusses the rationale for use of RVD as induction therapy and aims to provide guidance in prescribing this regimen in order to optimise efficacy while minimising the toxicities of treatment. We also highlight the increasing evidence for the utility of addition of a monoclonal antibody to the RVD backbone to deepen responses and potentially provide longer disease control.

Type of Medium: Online Resource

ISSN: 0007-1048 , 1365-2141

URL: Issue

URL: Article

DOI: 10.1111/bjh.v199.2

DOI: 10.1111/bjh.18295

Language: English

Publisher: Wiley

Publication Date: 2022

detail.hit.zdb_id: 1475751-5

In: Annals of Blood, AME Publishing Company, Vol. 3 ( 2018-12), p. 48-48

Type of Medium: Online Resource

ISSN: 2521-361X

URL: Journal

URL: Article

DOI: 10.21037/aob

DOI: 10.21037/aob.2018.12.02

Language: Unknown

Publisher: AME Publishing Company

Publication Date: 2018

In: Bone Marrow Transplantation, Springer Science and Business Media LLC, Vol. 56, No. 3 ( 2021-03), p. 738-740

Type of Medium: Online Resource

ISSN: 0268-3369 , 1476-5365

URL: Article

DOI: 10.1038/s41409-020-01086-9

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2021

detail.hit.zdb_id: 2004030-1

In: Expert Review of Hematology, Informa UK Limited, Vol. 11, No. 10 ( 2018-10-03), p. 817-828

Type of Medium: Online Resource

ISSN: 1747-4086 , 1747-4094

URL: Article

DOI: 10.1080/17474086.2018.1517040

Language: English

Publisher: Informa UK Limited

Publication Date: 2018

In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 21-21

Abstract: Background: There is limited data to guide prescribing of all available anticoagulants in obese patients, in particular those weighing & gt; 150kg or with a BMI & gt; 40kg/m2. We aimed to examine anticoagulant prescribing patterns in obese patients in Australia and New Zealand including choice of agent and dosing, determine whether patients with obesity achieve appropriate direct oral anticoagulant (DOAC) levels and evaluate the efficacy and safety of anticoagulation in obese patients. Methods: Patients with a BMI & gt; 35kg/m2 or weight & gt; 120kg receiving anticoagulant therapy are prospectively identified at 7 sites in Australia and New Zealand. Demographic data, indication for anticoagulation and choice of anticoagulant are collected at baseline. At follow-up visits, drug specific levels, dose adjustments and clinical progress (symptoms, imaging, recurrent thrombosis and adverse events) are recorded. Results: 155 patients have been recruited across seven sites (recruitment ongoing). The median age of patients was 53 (range 22-85) and 49% of patients were male. 77 (50%) of patients were anticoagulated for pulmonary embolus (PE) while 40% were anticoagulated for deep vein thrombosis (DVT) without PE. Initial anticoagulant prescribed was apixaban in 37 patients, dabigatran in 4 patients, rivaroxaban in 57 patients, low molecular weight heparin (LMWH) in 29 patients and warfarin in 28 patients (Table 1). A subset of patients initially received LMWH for 5-14 days prior to transition to a DOAC (rivaroxaban in 7, dabigatran in 6). There was cross-over between agents during the study period. Table 2 demonstrates median peak and trough DOAC levels. All peak apixaban levels and 25 of 37 (68%) peak rivaroxaban levels were within the therapeutic ranges published by the International Council for Standardization in Haematology (Gosselin, Thromb Haemost. 2018). Assessment of appropriate trough levels was limited by the limit of detection at different laboratories. 27 patients receiving enoxaparin had at least one peak Anti-Xa level (target peak 0.5-1.2U/ml). The median enoxaparin dose to achieve therapeutic peak Anti-Xa was 0.9mg/kg (range 0.52-1.3). 15 patients weighing & gt; 150kg had a recorded peak Anti-Xa, 10 of these patients were prescribed a capped dose of 150mg BD (weight range 155-290kg) and nine had a therapeutic Anti-Xa and one had a supratherapeutic Anti-Xa measurement. One patient had a PE on apixaban 5mg twice daily (in the setting of suspected non-compliance), one patient had a new confirmed PE after 4 days of non-compliance with rivaroxaban 20mg daily and another patient had a confirmed recurrence on therapeutic warfarin. 1 patient had a PE when warfarin was withheld for emergency surgery. An equivocal recurrence occurred on enoxaparin with a supratherapeutic Anti-Xa (1.76 U.ml) and 1 DVT occurred on dabigatran for a cardiac indication (no drug level available). One patient had recurrent superficial thrombophlebitis on rivaroxaban 20mg daily (peak 301ng/L and trough & lt;30ng/L). There was one episode of life-threatening gastrointestinal bleeding on dabigatran. Conclusion: There is limited data to guide prescribing of all anticoagulants in obese patients, in particular in patients weighing & gt; 150kg or BMI & gt; 40kg/m2. There is increasing use of DOACs in Australia and New Zealand in patients with obesity given the ease of administration and lack of monitoring required. Despite the recommendation to perform DOAC levels in this group of patients, interpretation of levels is difficult due to a lack of well validated therapeutic ranges with clinical correlation. Further data regarding the clinical utility of DOAC levels, appropriate dosing strategy for enoxaparin, and clinical outcomes in this population is required. Our registry provides data regarding drug levels in this population, prescribing characteristics and clinical outcome data. Disclosures No relevant conflicts of interest to declare.

Type of Medium: Online Resource

ISSN: 0006-4971 , 1528-0020

URL: Article

DOI: 10.1182/blood-2020-143150

Language: English

Publisher: American Society of Hematology

Publication Date: 2020

detail.hit.zdb_id: 1468538-3

detail.hit.zdb_id: 80069-7