Primary prevention of venous thromboembolism with apixaban for multiple myeloma patients receiving immunomodulatory agents

Cornell, Robert F.; Goldhaber, Samuel Z.; Engelhardt, Brian G.; Moslehi, Javid; Jagasia, Madan; Harrell, Shelton; Rubinstein, Samuel M.; Hall, Robert L.; Wyatt, Houston; Piazza, Gregory

doi:10.1111/bjh.16653

Cited by 41 publications

(36 citation statements)

References 33 publications

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“…Three recent studies comprising 224 patients in total have evaluated VTE and bleeding rates with the use of apixaban at 2.5 mg twice daily for at least 6 months, with no recorded VTE events while on anticoagulation (two events were recorded after the cessation of anticoagulation due to medication-induced thrombocytopaenia). This apparent efficacy may come with an increased bleeding risk, as the pooled data reveal two episodes of major haemorrhage and 14 episodes of clinically relevant non-major haemorrhage [14][15][16]. Although the data are not validated in comparison to another method of thromboprophylaxis in a randomised trial, the results of this study showing no VTE events in any patient actively using apixaban are encouraging.…”

Section: Discussionmentioning

confidence: 79%

Validation of Risk-Adapted Venous Thromboembolism Prediction in Multiple Myeloma Patients

Barrett

Quinn

Lavin

et al. 2021

JCM

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Multiple myeloma (MM) is associated with an increased risk of venous thrombosis (VTE). In the United Kingdom Medical Research Council (MRC) XI study of patients treated with immunomodulatory therapy, the VTE rate was 11.8% despite 87.7% of the patients being on thromboprophylaxis at the time of thrombosis. In order to effectively prevent VTE events in MM patients, a better understanding of patient and disease risk factors that might predict thrombosis is required. We performed a retrospective cohort analysis of over 300 newly diagnosed MM patients at a tertiary referral centre to determine the VTE rate, predictive factors for VTE, value of the Khorana score for MM VTE events and long-term mortality outcomes. Fifty-four percent of the patients were receiving thromboprophylaxis at the time of the VTE event. The mortality odds ratio was 3.3 (95% CI, 2.4–4.5) in patients who developed VTE in comparison to age-matched controls with MM. A younger age at diagnosis and higher white cell count (WCC) were found to be predictive of VTE events. Our data suggest that standard thromboprophylaxis may not be effective in preventing VTE events in myeloma patients, and alternative strategies, which could include higher-intensity thromboprophylaxis in young patients with a high WCC, are necessary.

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Section: Discussionmentioning

confidence: 79%

Validation of Risk-Adapted Venous Thromboembolism Prediction in Multiple Myeloma Patients

Barrett

Quinn

Lavin

et al. 2021

JCM

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“…No cases of symptomatic VTE were identified over a 6-month observation period. 84 Preliminary data suggest that apixaban may be an effective VTE prevention agent in myeloma patients receiving cycled dexamethasone.…”

Section: Considerations For Doac Induction Interactionsmentioning

confidence: 99%

Potential Dexamethasone–Direct Oral Anticoagulant Drug Interaction: Is This a Concern in COVID?

et al. 2021

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Objective To evaluate the literature on a potential dexamethasone–direct oral anticoagulant (DOAC) drug interaction and provide management considerations with COVID hypercoagulability. Data Sources A search of EMBASE, PubMed, and Google Scholar (January 1990 to May 2021), limited to the English language, using applicable search terms resulted in 137 articles, with 21 relevant articles included. Regulatory agency and clinical guidance documents were also reviewed. Study Selection and Data Extraction Included articles describe in vitro or in vivo animal or human data for dexamethasone induction of cytochrome P450 (CYP) 3A4 or P-glycoprotein (P-gp). Data Synthesis Dexamethasone has the potential to interact with the DOACs via CYP3A4 and/or P-gp induction. Only apixaban and rivaroxaban have CYP3A4 metabolism. Dexamethasone can increase CYP3A4 activity by up to 70% and reduce the area under the concentration-time curve (AUC) of CYP3A4 substrates by >40%, which is consistent with criteria for a weak CYP inducer. In rodents, dexamethasone P-gp induction is associated with AUC reductions of 20% to 50%. Human data are lacking. Relevance to Patient Care and Clinical Practice Severe COVID-19 infection is associated with hypercoagulability. Although heparins are the preferred anticoagulants for hospitalized COVID-19 patients, DOACs are being utilized. Dexamethasone is recommended for hospitalized COVID-19 patients requiring supplemental oxygen. The concurrent use of dexamethasone and apixaban or rivaroxaban in such patients carries the potential for reduced anticoagulant effect during a state of heightened thrombotic risk. Conclusions Concurrent use of dexamethasone and apixaban or rivaroxaban in hospitalized COVID-19 patients with laboratory evidence of COVID coagulopathy should be avoided until higher-quality data are available.

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“…Therefore, ongoing studies are evaluating the risk/benefit profile of novel oral anticoagulants. In a pilot study assessing primary prevention of VTE in MM patients treated with lenalidomide or pomalidomide, apixaban was well-tolerated without major hemorrhage events and effectively protected against VTE, stroke and myocardial infarction in the 6-month follow-up [ 121 , 122 ].…”

Section: Drug-specific Non-hematological Adverse Events Of Special Interestmentioning

confidence: 99%

Management of Adverse Events and Supportive Therapy in Relapsed/Refractory Multiple Myeloma

Pozzi

Bari

Pecherstorfer

et al. 2021

Cancers

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Relapsed/refractory (RR) multiple myeloma (MM) patients are a fragile population because of prolonged drug exposure and advanced age. Preserving a good quality of life is of high priority for these patients and the treatment of disease- and treatment-related complications plays a key role in their management. By preventing and limiting MM-induced complications, supportive care improves patients’ outcome. Erythropoietin-stimulating agents and bisphosphonates are well-established supportive strategies, yet novel agents are under investigation, such as anabolic bone agents and activin receptor-like kinase (ALK) inhibitors. The recent dramatic changes in the treatment landscape of MM pose an additional challenge for the routine care of RRMM patients. Multidrug combinations in first and later lines increase the risk for long-lasting toxicities, including adverse cardiovascular and neurological events. Moreover, recently approved first-in-class drugs have unique side-effect profiles, such as ocular toxicity of belantamab mafodotin or gastrointestinal toxicity of selinexor. This review discusses current standards in supportive treatment of RRMM patients, including recommendations in light of the recent SARS-CoV-19 pandemic, and critically looks at the incidence and management of side effects of standard as well as next generation anti-MM agents.

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Primary prevention of venous thromboembolism with apixaban for multiple myeloma patients receiving immunomodulatory agents

Cited by 41 publications

References 33 publications

Validation of Risk-Adapted Venous Thromboembolism Prediction in Multiple Myeloma Patients

Validation of Risk-Adapted Venous Thromboembolism Prediction in Multiple Myeloma Patients

Potential Dexamethasone–Direct Oral Anticoagulant Drug Interaction: Is This a Concern in COVID?

Management of Adverse Events and Supportive Therapy in Relapsed/Refractory Multiple Myeloma

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