Multiple myeloma is a heterogeneous disease with variable survival; this variability cannot be fully explained by the current systems of risk stratification. Early mortality remains a serious obstacle to further improve the trend toward increased survival demonstrated in recent years. However, the definition of early mortality is not standardized yet. Importantly, no study has focused on the impact of comorbidity on early mortality in multiple myeloma to date. Therefore, we analyzed the role of baseline comorbidity in a large populationbased cohort of 621 real-life myeloma patients over a 31-year period. To evaluate early mortality, a sequential multivariate regression model at 2, 6, and 12 months from diagnosis was performed. It was demonstrated that comorbidity had an independent impact on early mortality, which is differential and time-dependent. Besides renal failure, respiratory disease at 2 months, liver disease at 6 months, and hepatitis virus C infection at 12 months, were, respectively, associated with early mortality, adjusting for other well-established prognostic factors. On the other hand, the long-term monitoring in our study points out a modest downward trend in early mortality over time. This is the first single institution population-based study aiming to assess the impact of comorbidity on early mortality in multiple myeloma. It is suggested that early mortality should be analyzed at three key time points (2, 6, and 12 months), in order to allow comparisons between studies. Comorbidity plays a critical role in the outcome of myeloma patients in terms of early mortality.Am. J. Hematol. 91:700-704,

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performance status score, the presence of high-risk cytogenetic abnormalities by FISH including IgH translocations such as t(4;14) or t(14;16), del17p or abnormalities of chromosome 1, and ISS. Renal function was assessed by serum creatinine (sCr, mg/dL) and the estimated glomerular filtration rate (eGFR) according to the MDRD (modification of diet in renal disease) formula. Other variables of increasing interest were also included, such as the body mass index (BMI), the occurrence of weight loss before diagnosis, the delay in diagnosis (time from the first MM-related event to the bone marrow examination) as well as the therapeutic delay (time from bone marrow examination to date of initial treatment), the serum free light chain involved/uninvolved ratio (FLCr i/u), lactate dehydrogenase (LDH), C reactive protein, and the percentage of bone marrow plasma cell (BMPC) as measured by morphology. Patients were treated with conventional chemotherapy until 2006, when we started to use a bortezomib-based induction approach. ASCT has been used since 1995. Median overall survival (OS) was calculated in months (m) from the date of diagnosis (first bone marrow aspirate or biopsy) until