B-cell malignancies are a type of cancer that forms in a B-cells which are part of the immune system. Bruton tyrosine kinase inhibitor (BTKi) therapies have been approved by regulatory agencies including the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) to treat various B-cell malignancies. However, the safety of these treatments is not entirely known. Patients in clinical trials of BTKi therapies have developed cardiovascular disease, haemorrhage, liver injury, serious infections and new cancers (not including cancers that developed out of the B-cell cancer) so-called secondary primary malignancies (SPMs). This study will provide information on how often people with B-cell malignancies develop these conditions regardless of what cancer treatment they receive. This will provide information on how often these events are “expected” in people with B-cell malignancies. This information will then be compared to how often these events occur in clinical trials and other studies of BTKi therapies, including zanubrutinib, to see if these events are more common than “expected” when people receive these treatments.
Bruton tyrosine kinase inhibitor (BTKi) therapies have been approved by U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) for treatment of various B-cell malignancies. However, the safety profile of these treatments has not been well established. This objective of this study is to provide background rates of various adverse outcomes in a population of patients with B-cell malignancies for comparison to those observed in clinical trials and other observational studies of BTKi therapies, including zanubrutinib. This is a descriptive cohort study with no a priori hypothesis. We will select all patients with a diagnosis code for a B-cell malignancy recorded in CPRD GOLD or CPRD Aurum in years 2005 – 2021. In this cohort and separately by data source (GOLD versus Aurum), we will use Byar’s method to estimate the incidence rates with 95% confidence intervals of secondary primary malignancies (SPMs), cardiovascular disease (CVD) (e.g., cardiovascular death, myocardial infarction, stroke, arrhythmias, heart failure, hypertension (HTN)), haemorrhage, liver injury and serious infections) for all B-cell malignancies and by type (e.g., chronic lymphocytic leukaemia, mantle cell malignancies, etc.). Analyses of hospitalized outcomes will be conducted in the population of patients eligible for linkage to HES APC and will include cases recorded in HES APC, ONS death registry or GP records. We will create subpopulations with inclusion/exclusion criteria consistent with various clinical trials and observational studies of BTKi therapies. We will informally descriptively compare the incidences of each outcome in these study specific sub-cohorts to those observed in the respective trials/observational studies. This study will provide important information on rates of adverse events among patients with B-cell malignancies in the United Kingdom (UK). This study will also provide background information for the safety profile of treatments for B-cell malignancies that may be prescribed to patients in the UK and worldwide.
Secondary primary malignancy; incident cardiovascular diseases (e.g., myocardial infarction, stroke, arrhythmias heart failure, hypertension); cardiovascular death; haemorrhage; liver injury; serious infections [additional outcomes may be added by RDG protocol amendment if requested by regulatory agencies or are observed in clinical trials or post-marketing surveillance]
Susan Jick - Chief Investigator - BCDSP - Boston Collaborative Drug Surveillance Program
Rebecca Persson - Corresponding Applicant - BCDSP - Boston Collaborative Drug Surveillance Program
Catherine Vasilakis-Scaramozza - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
Katrina Hagberg - Collaborator - BCDSP - Boston Collaborative Drug Surveillance Program
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation