Abstract
Introduction: Despite treatment advances, multiple myeloma (MM) remains an incurable disease that may eventually become therapy resistant, leading to significant life years lost. Although overall survival (OS) is acknowledged as an important outcome, treatment effect on OS can be confounded by the impact of post study therapies and readout often takes several years, making the more immediate measures such as progression-free survival or minimal residual disease (MRD) very relevant. OS is a complex endpoint as it is impacted by treatment selection/combinations used, safety of these combinations, and resistance developed. Therefore, a thorough assessment of life-years lost is needed to inform policy and coverage decisions. The objective of this research is to synthesize cross-country data on years of life lost (YLL) to MM.
Methods: A targeted literature review assessed information on YLL, disability-adjusted life years (DALY), and incidence and prevalence of MM from global epidemiological and national databases. To account for incomplete data availability and maintain data integrity, analysis was restricted to Organization for Economic Co-operation and Development (OECD) or Group of 20 (G20) countries. The search terms, sources, and dates were documented in an Excel file along with the results; one reviewer conducted the searches and extractions, which were independently validated by a second reviewer. Only English language sources, or websites that could be translated automatically via Google were considered for inclusion. In this analysis, YLL is defined as number of years of life a person would have experienced without the disease (given their age and gender), minus the age they actually died with a particular disease. Therefore, this does not correspond to life expectancy at diagnosis but rather is a statistical measure of population mortality burden. DALY is defined as the years of life lost plus a weighted measure of years lived with disease such that it captures both mortality and morbidity.
Results: Two global databases were identified (Global Burden of Disease 2021, World Health Organization 2022). Country- and regional-specific databases were identified for some larger health economies, but these were judged to be unsuitable for the purpose of cross-country comparison. Cross-country data on outcomes were only available for overall MM, with data on relapsed/refractory MM (RRMM) only available in some country-specific datasets. YLL to MM were substantial across all countries. Across all countries in the sample, a total of 2.05 million years of life were lost to MM each year. The median mortality burden in the sample was 97.70 YLL per 100,000 people in OECD/G20 countries (interquartile range [IQR] 55.25–107.24). When adjusted for prevalence, the median YLL was 4.95 per patient with MM (IQR 3.39–7.86). DALY were also substantial across countries in the sample. 2.13 million DALY were generated by MM each year. The median DALY burden in the sample was 98.08 per 100,000 people (IQR 56.82–113.40). When adjusted for prevalence, the median DALY per patient with MM was 5.16 (IQR 3.58–8.06).
Conclusions: MM results in substantial mortality burden across all countries included in the sample, which is consistent with data on other rare hematological malignancies such as acute myeloid leukemia (average 93 YLL). The data imply that patients miss out on nearly 5 years of life due to the disease. Carers and families will also be affected by the mortality associated with MM, through the missing life years of loved ones. As this study included patients currently living with MM, it could potentially underestimate the true YLL burden of MM, especially for newly diagnosed patients. The next step of this research is to conduct Delphi interview panels with clinicians to identify what factors drive the high mortality burden of MM, and especially to identify the impact that RRMM treatment pathways might have on the overall mortality burden of MM. This research highlights the significant mortality burden of MM across countries and emphasizes the need for new treatments that improve survival.
