Thrombosis in multiple myeloma (MM)

Cesarman‐Maus, Gabriela; Braggio, Esteban; Fonseca, Rafaël

doi:10.1179/102453312x13336169156933

Cited by 43 publications

(32 citation statements)

References 32 publications

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“…For instance, dasatinib rarely induces pleural effusions or pulmonary hypertension, although the vascular issues noted with nilotinib are completely different and likely represent progressive atherosclerosis . In addition, combination therapies used in myeloma may increase the risk of venous and arterial thrombotic events . Overall, it is fair to say that these myriad vascular complications are important and ultimately require specific strategies to manage them effectively.…”

Section: Common CV Adverse Eventsmentioning

confidence: 99%

Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management

Curigliano

Cardinale

Dent

et al. 2016

CA A Cancer J Clinicians

598

427

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Answer questions and earn CME/CNE Cancer and heart disease are the leading causes of morbidity and mortality in the industrialized world. Modern treatment strategies have led to an improvement in the chances of surviving a diagnosis of cancer; however, these gains can come at a cost. Patients may experience adverse cardiovascular events related to their cancer treatment or as a result of an exacerbation of underlying cardiovascular disease. With longer periods of survival, late effects of cancer treatment may become clinically evident years or decades after completion of therapy. Current cancer therapy incorporates multiple agents whose deleterious cardiac effects may be additive or synergistic. Cardiac dysfunction may result from agents that can result in myocyte destruction, such as with anthracycline use, or from agents that appear to transiently affect left ventricular contractility. In addition, cancer treatment may be associated with other cardiac events, such as severe treatment-induced hypertension and vasospastic and thromboembolic ischemia, as well as rhythm disturbances, including QTc prolongation, that may be rarely life-threatening. Early and late effects of chest radiation can lead to radiation-induced heart disease, including pericardial disease, myocardial fibrosis, cardiomyopathy, coronary artery disease, valvular disease, and arrhythmias, in the setting of myocardial fibrosis. The discipline of cardio-oncology has developed in response to the combined decision making necessary to optimize the care of cancer patients, whether they are receiving active treatment or are long-term survivors. Strategies to prevent or mitigate cardiovascular damage from cancer treatment are needed to provide the best cancer care. This review will focus on the common cardiovascular issues that may arise during or after cancer therapy, the detection and monitoring of cardiovascular injury, and the best management principles to protect against or minimize cardiotoxicity during the spectrum of cancer treatment strategies. CA Cancer J Clin 2016;66:309-325. © 2016 American Cancer Society.

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Section: Common CV Adverse Eventsmentioning

confidence: 99%

Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management

Curigliano

Cardinale

Dent

et al. 2016

CA A Cancer J Clinicians

598

427

View full text Add to dashboard Cite

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“…The extraordinary advances in the therapeutic armamentarium available for patients with a new diagnosis of multiple myeloma or relapsed/recurrent disease has led to significant increases in overall survival (OS) but has also drawn attention to the management of treatment-related complications for these patients. Among the commonest complications seen in this population is venous thromboembolism (VTE), as more than 10% will develop VTE during the course of their disease [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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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“…4,5,9,10,14 Thrombosis, for example, can be observed in all stages of MM but there is an increased risk with immunomodulatory drugs when combined with dexamethasone, as well as with the combination of melphalan and prednisone. 15 Additionally, immune-mediated inflammatory diseases are associated with myelosuppression. 9,[16][17][18] Bortezomib is commonly associated with gastrointestinal (GI) adverse events (AEs), reactivation of herpes zoster, bone marrow sup- [19][20][21] Thalidomide is even more strongly implicated in PN, 22 and a recent analysis of patients with newly diagnosed MM revealed that although thalidomide improved efficacy when added to melphalan-prednisone, it negatively impacted safety.…”

Section: Introductionmentioning

confidence: 99%

Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies

Martin²,

et al. 2013

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Carfilzomib, a selective proteasome inhibitor, was approved in 2012 for the treatment of relapsed and refractory multiple myeloma. Safety data for single-agent carfilzomib have been analyzed for 526 patients with advanced multiple myeloma who took part in one of 4 phase II studies (PX-171-003-A0, PX-171-003-A1, PX-171-004, and PX-171-005). Overall analyses of adverse events and treatment modifications are presented, as well as specific analyses of adverse events by organ system. Overall, the most common adverse events of any grade included fatigue (55.5%), anemia (46.8%), and nausea (44.9%). In the grouped analyses, any grade adverse events were reported in 22.1% for any cardiac (7.2% cardiac failure), 69.0% for any respiratory (42.2% dyspnea), and 33.1% for any grouped renal impairment adverse event (24.1% increased serum creatinine). The most common non-hematologic adverse events were generally Grade 1 or 2 in severity, while Grade 3/4 adverse events were primarily hematologic and mostly reversible. There was no evidence of cumulative bone marrow suppression, either neutropenia or thrombocytopenia, and febrile neutropenia occurred infrequently (1.1%). Notably, the incidence of peripheral neuropathy was low overall (13.9%), including patients with baseline peripheral neuropathy (12.7%). Additionally, the incidence of discontinuations or dose reductions attributable to adverse events was low. These data demonstrate that single-agent carfilzomib has an acceptable safety profile in heavily pre-treated patients with relapsed/refractory multiple myeloma. The tolerable safety profile allows for administration of full-dose carfilzomib, both for extended periods and in a wide spectrum of patients with advanced multiple myeloma, including those with pre-existing comorbidities. ABSTRACTpression including thrombocytopenia, and dose-limiting peripheral neuropathy (PN) (up to 30% Grade 1/2 and 7-15% Grade 3/4). The PN often leads to discontinuation, and can be debilitating and occasionally irreversible. [19][20][21] Thalidomide is even more strongly implicated in PN, 22 and a recent analysis of patients with newly diagnosed MM revealed that although thalidomide improved efficacy when added to melphalan-prednisone, it negatively impacted safety. 23 Maintenance therapy, as well as consolidation strategies, with many of these drugs are being investigated as important ways to improve and prolong responses in patients with MM, 24 and these extended treatment periods may draw increased attention to tolerability and cumulative toxicities when considering longterm treatment options.Carfilzomib was initially evaluated in 2 phase I studies 25 and PX-171-002 26) investigating two different dosing schedules: 5 consecutive days of a 14-day cycle and 2 consecutive days/week for 3 weeks of a 28-day cycle). Consecutive day dosing demonstrated promising antitumor activity. However, single-agent carfilzomib administered using the 2 consecutive day dosing schedule (PX-171-002) was better tolerated and was chosen for further exploration in ph...

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Thrombosis in multiple myeloma (MM)

Cited by 43 publications

References 32 publications

Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management

Cardiotoxicity of anticancer treatments: Epidemiology, detection, and management

Multiple Myeloma and Thrombosis: Prophylaxis and Risk Prediction Tools

Integrated safety profile of single-agent carfilzomib: experience from 526 patients enrolled in 4 phase II clinical studies

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