Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma Receiving Immunomodulatory Therapy

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

doi:10.3389/fonc.2019.00045

Cited by 24 publications

(9 citation statements)

References 39 publications

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“…There is an ongoing single-arm phase IV study (NCT02958969) that aims to evaluate prospectively the safety and efficacy of apixaban for primary VTE prevention in MM patients. The primary objective is to assess VTE occurrence within six months in patients who receive IMiD-based therapy [96]. At interim analysis at three months, no VTE events and no major hemorrhage was reported [96].…”

Section: Thromboprophylaxis: To Doac or Not To Doac?mentioning

confidence: 99%

“…The primary objective is to assess VTE occurrence within six months in patients who receive IMiD-based therapy [96]. At interim analysis at three months, no VTE events and no major hemorrhage was reported [96]. Pergourie et al also recently presented data from the use of apixaban as prophylaxis in MM patients on IMiDs.…”

Section: Thromboprophylaxis: To Doac or Not To Doac?mentioning

confidence: 99%

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Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools

Fotiou

Gavriatopoulou

Terpos

2020

Cancers

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Thromboembolism in multiple myeloma (MM) patients remains a common complication that renders the optimization of our thromboprophylaxis practice necessary. This review aims to make clear the need for the development of more accurate risk assessment tools and means of thrombosis prevention. Current clinical practice is guided by available guidelines published by the IMWG in 2014, but the extent to which these are implemented is unclear. Recently, several groups developed clinical scores for thrombosis risk in MM in an attempt to improve risk stratification, but these have not been validated or used in clinical practice so far. Research in this field is increasingly focusing on understanding the unique coagulation profile of the MM patient, and data on potential biomarkers that accurately reflect hypercoagulability is emerging. Finally, promising evidence on the effectiveness of direct oral anticoagulants (DOACs) in the context of thrombosis prevention in MM patients is increasingly becoming available. The critical appraisal of the above research areas will establish the necessity of combining disease-specific clinical risk factors with coagulation biomarkers to allow more effective risk stratification that will eventually lead to the reduction of this significant complication. Results from ongoing clinical trials on the role of DOACs are much anticipated.

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Section: Thromboprophylaxis: To Doac or Not To Doac?mentioning

confidence: 99%

Section: Thromboprophylaxis: To Doac or Not To Doac?mentioning

confidence: 99%

Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools

Fotiou

Gavriatopoulou

Terpos

2020

Cancers

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“…LMWH or full dose warfarin with a target international ration of 2 - 3 is recommended for patients with ≥ 2 risk factors for VTE including advanced age, history of VTE, recent surgery, degree of disease burden, or combination steroid therapy [ 4 ]. Direct oral anticoagulants are not currently advised; however, there is an ongoing prospective randomized controlled trial of apixaban 2.5 mg twice daily versus to evaluate the rate of VTE in this population over 6 months [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Vein Thrombosis in a Patient With Multiple Myeloma on Treatment With Lenalidomide

et al. 2021

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Multiple myeloma (MM) poses inherent risk of thrombosis that can be amplified by the use of immunomodulator therapy. We present a patient with MM who was being treated with lenalidomide and dexamethasone when he developed progressive dyspnea on exertion consistent with a left lower pulmonary vein thrombosis (PVT) despite use of prophylactic aspirin. The PVT was not initially seen on standard computed tomography angiogram pulmonary embolism protocol but was seen on 192-slice multidetector computed tomography angiogram for assessment of coronary calcifications 8 months later. Subsequent treatment with full dose rivaroxaban resulted in full clot resolution and symptom improvement. PVT has not been previously reported with lenalidomide therapy and may not be a forefront differential diagnosis. In such cases, a multi-modality diagnostic approach may be beneficial. Consideration should be given to escalating venous thromboembolism prophylaxis to full dose anticoagulation during increased prothrombotic windows, such as the time of treatment initiation or dose adjustments, in low bleeding risk patients.

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“…Several studies have in fact shown a promising efficacy of the new oral anticoagulants (DOACs) in preventing thrombosis in cancer patients, including MM [40,49,51,55]. Recent studies also showed that apixaban, especially at low dose, was safe and effective for thromboprophylaxis in relatively small series of MM patients receiving an IMiD-containing regimen as first line treatment or for relapsed disease [53].…”

Section: Discussionmentioning

confidence: 99%

“…These recommendations were then taken up and confirmed by the 2015 European Myeloma Network (EMN) [ 38 ] and 2017 ESMO guidelines [ 39 ]. Limited data are available about thrombotic risk in patients on treatment with pomalidomie but, as with the other IMiDs, it seems to determine an increased risk of thrombosis [ 17 , 25 , 40 , 41 , 42 , 43 , 44 ]. With regard to the second-generation proteasome inhibitor Carfilzomib, phase III trial ASPIRE, which compares the efficacy of lenalidomide-dexamethasone versus carfilzomib-lenalidomide-dexamethasone, shows a higher incidence of VTE in the three-drugs arm (13% vs. 6%), despite the mandatory use of thromboprophylaxis [ 45 ].…”

Section: Introductionmentioning

confidence: 99%

A Real-Life Survey of Venous Thromboembolic Events Occurring in Myeloma Patients Treated in Third Line with Second-Generation Novel Agents

Calafiore

Giamporcaro

Conticello

et al. 2020

JCM

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Compared to the general population, patients with multiple myeloma (MM) have a nine-fold increased risk of developing venous thromboembolism (VTE). Little is known about VTE prophylaxis in relapsed/refractory (RR) MM patients treated with next generation anti-myeloma drugs, such as pomalidomide (Poma) and carfilzomib (K), and monoclonal antibodies daratumumab (Dara) and elotuzumab (Elo), alone or in combination with dexamethasone at high- (D, 40 mg/week) or low-dose (d, 20 mg/week). Here, we describe the incidence of VTE in a retrospective cohort of 112 consecutive relapsed and refractory myeloma (RRMM) patients who received a third line of treatment from April 2013 to February 2020. Anti-MM regimens included combinations of pomalidomide and dexamethasone (PomaD, N = 61), carfilzomib, lenalidomide and dexamethasone (KRd, N = 31), and elotuzumab, lenalidomide and dexamethasone (EloRd, N = 10), while the remaining 10 patients received daratumumab as a single agent. According to National Comprehnsive Cancer Network (NCCN), International Myeloma Working Group (IMWG) and 2015 European Myeloma Network (EMN) guidelines, 42 patients (38%) were classified as high-risk patients. According to the IMPEDE VTE score, 32 patients (28%) were classified as low-risk, with a score ≤ 3 (most of them in the PomaD and Dara group), 70 (63%) were classified as intermediate-risk, with a score of 4–7 (most of them in PomaD and KRd group), and 10 (9%) were classified as high-risk, with a score ≥8 (most of them in the PomaD group). All patients received a prophylaxis, consisting generally of low-doses of acetylsalicylic acid. VTE was recorded in 9% of our patients, all of them with an intermediate or high-risk IMPEDE score, treated with low doses aspirin (ASA). No VTE occurred in patients treated with daratumumab. Thus, our real-life experience documents that (1) in RRMM patients treated with continuative regimens of third line, the incidence of VTE is similar to the setting of newly-diagnosed patients; (2) many patients in real-life received prophylaxis with ASA, irrespective of the risk classification; (3) the IMPEDE VTE score seems to be more appropriate to define the risk categories. Randomized clinical trials are required to better define the VTE prophylaxis strategy in the RRMM setting.

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Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma Receiving Immunomodulatory Therapy

Cited by 24 publications

References 39 publications

Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools

Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools

Pulmonary Vein Thrombosis in a Patient With Multiple Myeloma on Treatment With Lenalidomide

A Real-Life Survey of Venous Thromboembolic Events Occurring in Myeloma Patients Treated in Third Line with Second-Generation Novel Agents

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