Cardiac Event Rates in Patients with Newly Diagnosed and Relapsed Multiple Myeloma in US Clinical Practice.

Factors contributing to cardiac comorbidity in patients, typically elderly, with multiple myeloma (MM) include age-related cardiac risks as well as disease related factors such as amyloid infiltration, hyperviscosity, A-V shunting and chronic anemia (McBride, 1988; Robin, 2008; Inanir, 1998). Cardiac effects, associated with anthracycline therapy and transplant, have been reported with alkylating agents (myopericarditis, acute cardiomyopathy), immunomodulatory drugs (IMiDs) (arrhythmias, myocardial infarction) and proteasome inhibitors (congestive heart failure [CHF]) (Kyle, 2003; Chow, 2011; Revlimid PI 2012; Velcade PI 2012; Singhal S, 2011). Estimating the frequency of cardiac adverse events (AEs) in MM patients would help in understanding the magnitude of these risks and would provide context for rates of observed AEs. To our knowledge, this is the first analysis to examine the incidence and prevalence of cardiac AEs in patients with MM.

We conducted a retrospective cohort study in the US using the MarketScan^® commercial and Medicare supplemental insurance claims database from January 1, 2006 to December 31, 2011. Adult patients were included with a MM diagnosis following 6 months of continuous enrollment (baseline period) and no gaps in insurance coverage >31 days. Newly diagnosed MM patients were analyzed separately from patients with relapsed MM, defined as patients previously treated with ≥3 regimens (bortezomib, IMiDs, and alkylating agents or anthracyclines). Study entry date for newly diagnosed patients was the MM diagnosis date and, for the relapsed patients, the date patients' met the criteria of having received ≥3 regimens. Diagnosis, procedure and treatment codes (ICD-9, HCPCS, and NDC) were used to classify patients. The study period was defined as the duration from study entry date to study end (i.e., December 31, 2011 or the end of continuous enrollment or prescription drug coverage). Cardiac AEs were captured separately for inpatient, outpatient, and any site of care, and included any cardiac event, CHF, ischemic heart disease (IHD), and arrhythmias. Cardiac events present during baseline were identified as comorbidities.

N=32,193 patients met inclusion criteria, the majority were newly diagnosed. The mean time on study ranged from 12 to 18 months (max 5 yrs). The mean age was 63 yrs, and approximately 50% of subjects were male. Cardiac comorbidities were common; nearly two-thirds of patients had baseline cardiac events, of which arrhythmias and IHD were most frequent. While on study, the incidence of any cardiac AE was 72% for newly diagnosed and 71% for relapsed patients. The most common cardiac events during the study period were arrhythmias, IHD, and CHF. In general, event rates were similar between newly diagnosed and relapsed patients (Table 1).

This retrospective study provides the first estimates of cardiac AE rates in a large population of MM patients, both newly diagnosed and relapsed, in a clinical practice setting in the US. During the study period, regardless of treatment stage of disease, nearly three quarters of MM patients experienced a cardiac AE. These results demonstrate a high prevalence of cardiac comorbidities and occurrence of cardiac events in MM patients, especially arrhythmias and heart failure, regardless of relapse status and type of anti-MM treatment.

Kistler:Onyx: Consultancy, Research Funding. Rajangam:Onyx: Employment. Faich:Onyx: Consultancy, Research Funding. Lanes:Onyx: Consultancy, Research Funding.