The incidence of second primary malignancies (SPMs) in long-term survivors of multiple myeloma (MM) is increasing because of increased life expectancy. We retrospectively analyzed the risk factors for SPMs in patients with MM after autologous stem cell transplantation (ASCT) before and after the introduction of proteasome inhibitors and immunomodulatory drugs (IMiDs). In total, 2340 patients newly diagnosed with MM who underwent ASCT between 1995 and 2016 were enrolled in this study. Forty-three patients developed SPMs (29 solid, 12 hematological, and 2 unknown tumors), with cumulative incidence rates of 0.8% and 2.5% at 24 and 60 months, respectively. The cumulative incidence rates of hematological and solid SPMs at 60 months were 0.8% and 1.8%, respectively. The overall survival (OS) rate at 60 months after ASCT was 62.9% and the OS rates after the diagnosis of SPMs at 24 months were 72.2% for hematological SPMs and 70.9% for solid SPMs. Multivariate analysis revealed that the use of IMiDs (P = 0.024) and radiation (P = 0.002) were significant independent risk factors for SPMs. The probabilities of developing SPMs and death due to other causes (mainly MM) at 60 months were 2.5% and 36.5%, respectively, indicating that the risk of SPMs was lower than that of death from MM. Furthermore, SPMs between the pre-novel and novel agent eras (ASCT between 2007 and 2016) groups significantly increased (1.9% vs. 4.3% at 60 months, P = 0.022). The early occurrence of SPMs after ASCT should be monitored cautiously.
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