Abstract
Objective: Multiple myeloma (MM) is a rare condition, that is, one defined by the European Medicines Agency as affecting no more than 5 in 10,000 people in the EU. It is also the second most common hematologic malignancy. MM is particularly burdensome because most patients eventually relapse and develop refractory disease. To help characterize the epidemiological burden and trends associated with the condition we conducted a systematic literature review to identify published evidence on outcomes including overall incidence and prevalence and survival in patients with relapsed (R) or relapsed and refractory (RR) MM.
Methods: We searched the MEDLINE and Embase databases for articles in English published between 2003 and 2013. Identified studies were initially screened using information in the title and abstract, and then by examining the full text using predefined inclusion and exclusion criteria. These criteria specified that to be included, studies had to have reported real-world data on the incidence or prevalence of MM or survival in patients with RMM/RRMM in the following countries: Australia, Austria, Belgium, Brazil, Canada, France, Germany, Italy, Korea, Mexico, the Netherlands, Spain, Sweden, Switzerland, Taiwan, and the UK. To improve generalizability, only studies with a sample size of 100 patients or more were included.
Results: The review identified a total of 1,632 studies across MEDLINE and Embase. Following screening, 22 studies met the predefined selection criteria (as described above in the Methods section). Most studies (n=21) were retrospective in design, of which 10 studies reported on incidence and/or prevalence outcomes and 12 on survival. Specifically, incidence was reported for populations in Brazil (n=1), Canada (n=1), France (n=1), Germany (n=1), Italy (n=1), Korea (n=3), and Taiwan (n=2); two of these studies also reported prevalence data for populations in Brazil and Korea. The studies on survival included patients who received a range of 1 to 9 previous treatments for MM and were conducted in Canada (n=1), France (n=1), Germany (n=2), Italy (n=4), South Korea (n=1), Spain (n=1) and the UK (n=2). No published studies for any of the outcomes of interest were identified for populations in the following countries: Australia, Austria, Belgium, Mexico, the Netherlands, Sweden, or Switzerland. In the studies that reported a crude (i.e., age-unadjusted) incidence for MM, the incidence ranged from around 1.4 to 2.1 cases per 100,000 population per year. Of note, the incidence was found to have risen in recent decades, from 1.0 case per 100,000 population in 1999 to 1.5 cases per 100,000 in 2009 in Korea (a rise of 4.1% each year; p < 0.05) and from 0.36 cases per 100,000 in the period from 1979 to 1983 to 1.6 cases per 100,000 in 2009 in Taiwan (a 4.4-fold increase between these years). The prevalence of MM was 5.7 per 100,000 population from October 2009 to March 2010 in Brazil and 5.5 per 100,000 population in January 2010 in Korea. Among patients who received chemotherapy regimens to manage RMM/RRMM, overall survival ranged from 12.4 months in those treated with bendamustine (following a median of 4 previous lines of therapy that included alkylators, steroids, an immunomodulatory drug, and bortezomib) to 26.2 months for those treated with thalidomide with or without the use of salvage therapy (following a median of 1 prior therapy). One study that explored predictors of overall survival found that this outcome was significantly worse in patients who previously receive more lines of treatment (3 or above) compared with those who received fewer lines of treatment (18.1 months compared with 38.9 months, respectively; p = 0.019).
Conclusions: Recently published data on key epidemiological outcomes in MM are limited, even for several industrialized countries, perhaps reflecting the condition’s rare-disease status. The available evidence suggests that the incidence of MM has been rising in recent decades, though the overall incidence remains low enough for MM to still be considered a rare disease. Despite the range of chemotherapeutic options that are currently available, survival in patients who have RMM/RRMM is poor and worsens with each relapse and with increasing number of prior lines of treatment. This pattern of decreasing survival in later lines of treatment suggests the need for additional therapies to improve outcomes in MM and RMM/RRMM.
Disclosures
Rizzo: Onyx Pharmaceuticals, Inc., an Amgen subsidiary: Consultancy; Evidera: Employment. Xu:Onyx Pharmaceuticals, Inc., an Amgen subsidiary: Consultancy; Evidera: Employment. Iheanacho:Onyx Pharmaceuticals, Inc., an Amgen subsidiary: Consultancy; Evidera: Employment. Panjabi:Onyx Pharmaceuticals, Inc., an Amgen subsidiary: Employment, Equity Ownership.
Criteria and Scoring Functions Used in Multi-criteria Decision Analysis and Value Frameworks for the Assessment of Rare Disease Therapies: A Systematic Literature Review
