Clinical trial NCT05541978: Thrombosis in Patients With Multiple Myeloma in an University Medical Center
Official title: Thrombosis in Newly Diagnosed Multiple Myeloma Patients: a Clinical Audit of Intermediate Dose Low Molecular Weight Heparin
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Myeloma
Venous Thromboembolism
Arterial Thromboembolism
Lead sponsor: University Medical Center Groningen
Sponsor class: OTHER
First posted: 2022-09-15
Enrollment: 140
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This study seeks to include all available multiple myeloma patients treated in the UMCG. The inclusion of all patients is necessary in order to be able to calculate the incidence of venous thrombosis and in order to describe the use of thromboprophylaxis in these patients. Therefore all UCMG patients qualifying based on the inclusion and exclusion criteria will be included. We approximate that there are 60 new cases of multiple myeloma diagnosed per year in the UMCG. Thus, around 480 patients would be included in the study.

Brief summary: Main research question:

What is the present venous thrombosis incidence and what are the current practices of prescribing thromboprophylaxis in patients with multiple myeloma (MM)?

Design:

The present study is a retrospective cohort study. The patients will be selected from the electronic patient dossier (EPD) of the University Medical Center Groningen (UMCG). The present study will include newly diagnosed adult patients with a first MM at the UMCG between 1st of January 2014 and 1st of September 2021. The primary outcome of the study is the incidence of venous thromboembolism (VTE) with one year of diagnosis of MM. The investigators will also describe the various thromboprophylaxis regimens used and their corresponding VTE incidence. The secondary outcome will be the incidence of arterial thrombosis (AT) within the same period of time. Possible confounders are the therapy administered for MM, thromboprophylaxis type, age and patient comorbidities. Lastly, the third outcome will be a description of current thromboprophylaxis practices in the UMCG. Each outcome will be described separately.

Expected results:

Based on the study by de Waal et al in which they included 474 MM patients treated at the UMCG and at 4 hospitals in the province Friesland, the investigators expect to record a VTE incidence of approximately 15%.

Detailed description: Background:

Multiple myeloma (MM) is a neoplastic clonal proliferation of plasma cells causing a considerable worldwide burden of disease. In 2016 Western Europe was one of the regions with the highest MM incidence globally, with an age-standardized incidence of 4.6 per 100.000 (95% UI, 3.7-5.5). MM is associated with multiple complications which make the management of this disease particularly difficult. Moreover, patients with MM have a raised risk of venous thromboembolism (VTE) which substantially increases their mortality risk. The link between malignancy and the development of a hypercoagulable state has been extensively studied, with altered coagulation, patient comorbidities, tumour characteristics and treatment side-effects all playing a role in the pathogenesis of thrombosis in cancer. Specifically in MM, the increased VTE risk seems to be partially due to aberrations in haemostasis, such as acquired activated Protein C resistance and increased levels of Factor VIII and Von Willebrand Factor.

MM treatment and maintenance therapy has developed and improved substantially during the past decades, with immunomodulatory drugs (IMIDs), namely lenalidomide- or thalidomide-based regimens, being currently the most effective and used option. Nevertheless, one of the challenges of these regimens remains the associated elevated VTE risk, which is especially high in newly diagnosed MM patients treated with IMIDs and dexamethasone. Various mechanisms have been researched to explain the increased VTE risk. For instance, transiently decreased thrombomodulin levels during the first months of treatment have been associated with an increased thrombosis risk during the initial period of therapy. Moreover, high levels of cathepsin G have also been hypothesized to contribute to the high thrombosis incidence in MM patients undergoing treatment.

Choosing an appropriate thromboprophylaxis regimen in MM patients treated with IMIDs remains a challenge in clinical practice. Randomized controlled trials (RCTs) did not show a difference in the VTE risk between the use of aspirin or low molecular weight heparin (LMWH) in the management of MM patients. Furthermore, despite thromboprophylaxis, high VTE incidence remains a concerning problem in contemporary lenalidomide-based regimens. Therefore, the current study seeks to describe the use and efficacy of current thromboprophlaxis regimens in MM patients treated with IMIDs in an university medical center in order to assess the current VTE incidence and the effectiveness of thromboprophylaxis protocols in place.

Research question:

What is the present venous thrombosis incidence and what are the current practices of prescribing thromboprophylaxis in patients with multiple myeloma?

Design:

The present study is a retrospective cohort study. The patients will be selected from the electronic patient dossier (EPD) of the University Medical Center Groningen (UMCG). The present study will include newly diagnosed adult patients with a first MM at the UMCG between the 1st of January 2014 and 1st of September 2021. The primary outcome of the study is the incidence of VTE with one year of diagnosis of MM. The investigators will also describe the various thromboprophylaxis regimens used and their corresponding VTE incidence. The secondary outcome will be the incidence of arterial thrombosis (AT) within the same period of time. Possible confounders are the therapy administered for MM, thromboprophylaxis type, age and patient comorbidities. Lastly, the third outcome will be a description of current thromboprophylaxis practices in the UMCG. Each outcome will be described separately.

Expected results:

Based on the study by de Waal et al in which they included 474 MM patients treated at the UMCG and at 4 hospitals in the province Friesland, the investigators expect to record a VTE incidence of approximately 15%.

Eligibility criteria: Inclusion Criteria:

* Adult patients diagnosed with multiple myeloma between 1st of January 2014 and 1st of September 2021
* Patients diagnosed at UMCG
* Patients diagnosed with multiple myeloma based on the IMWG criteria

Exclusion Criteria:

* Patients first diagnosed with multiple myeloma before 1st of January 2014
* Patients diagnosed after 1st of September 2021
* Patients diagnosed with a relapse of multiple myeloma between 1st of January 2014 and 1st of September 2021 of a multiple myeloma diagnosed \<2014
* Patients who are marked as objecting to the use of their data for research purposes in the electronic patient dossier of UMCG

Primary outcomes:
measure: Venous thromboembolism incidence
timeFrame: 1 year
Secondary outcomes:
measure: Arterial thromboembolism
timeFrame: 1 year
Other outcomes:
measure: Frequency of thrombosis events per thromboprophylaxis regimen
timeFrame: 1 year
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen
Study officials:
affiliation: University Medical Center Groningen
name: Karina Meijer
role: PRINCIPAL_INVESTIGATOR
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