The clinical data of the patients with newly diagnosed multiple myeloma （NDMM） treated with proteasome inhibitor or immunomodulator-based chemotherapy were retrospectively analyzed. According to whether the overall survival （OS） was more than 24 months， they were divided into early death group （OS < 24 months） and control group （OS ≥ 24 months）. The high-risk factors of the patients in two groups were statistically analyzed， including age， International Staging System（ISS） stage， Revised Intenational Staging System （R-ISS） stage， anemia， renal insufficiency， hypercalcemia， increasing of lactate dehydrogenase（LDH） level， bone marrow plasma cell ratio， extramedullary plasmacytoma， detection results of fluorescence in situ hybridization（FISH），and efficacy.Kaplan Meier method was used to draw the survival curves for survival analysis， Logistic regression analysis was used for stepwise screening for the risk factors， and the meaningful clinical indicators were screened， and multivariate analysis was used to explore the high-risk factors of early death.

A total of 237 patients with NDMM were included， including 53 cases in early death group and 184 cases in control group. The median OS of the patients in early death group was 16 months， but the median OS of the patients in control group had not been reached by the end of follow-up. There was significant difference in OS of the patients between two groups （P<0.01）. The causes for death of the patients in early death group included disease progression death （77.4%） and non-disease progression death （22.6%）. The non-disease progression death included 4 cases of pneumonia， 3 cases of acute myocardial infarction， 1 case of acute cerebral infarction and 4 cases of ominous causes of death due to automatic abandonment of treatment. The univariate analysis results showed that the percentages of elderly patients （>65 years old）， ISS stage Ⅲ， R-ISS stage Ⅲ， anemia， increasing of LDH level，bone marrow plasma cells ratio> 60%， extramedullary plasma cell tumor， 17p deficiency detected by FISH and failure to reach partial response（PR） in early death group were higher than those in control group （P<0.05）.The multivariate regression analysis results showed that old age （P=0.007）， R-ISS stage Ⅲ （P=0.003）， extramedullary plasmacytoma （P=0.008） and failure to reach PR （P<0.01） were the independent risk factors for early death of the NDMM patients in the era of novel drugs.

The cause for early death in the era of novel drugs is disease progression； age> 65 years old， R-ISS stage Ⅲ， extramedullary plasmacytoma and the best curative effect not reaching PR are still the independent risk factors for early death of the NDMM patients. The intensive treatment of the NDMM patients with the above characteristics may improve the prognosis of the patients.