Risk of secondary primary malignancies in multiple myeloma patients with or without autologous stem cell transplantation

Outcomes for patients with multiple myeloma (MM) have improved through use of novel treatments, especially lenalidomide combined with autologous stem cell transplantation. However, because of their increased life expectancy, an increased risk of secondary primary malignancies (SPMs) has been observed in MM patients, particularly after lenalidomide maintenance in both transplant-eligible (TE) and transplant-ineligible (TI) patients. To evaluate the incidence and risk factors of developing SPMs, we identified 17 TE-MM and 12 TI-MM patients with SPMs among 211 TE-MM and 280 TI-MM patients, including seven TE-MM and four TI-MM patients with hematological malignancies and ten TE-MM and eight TI-MM patients with non-hematological cancers, respectively. The median follow-up time from diagnosis was > 4 years. Multivariate analysis identified a history of high-dose cyclophosphamide use for peripheral blood stem cell harvest in TE-MM patients and > 65 years of age at diagnosis, or a history of adriamycin, lenalidomide, or thalidomide use in TI-MM patients as independent risk factors for SPMs (P < 0.001). Patients with a history of lenalidomide use had a lower risk of death among both TE-MM (P = 0.0326) and TI-MM (P < 0.001) patients. The survival benefit of receiving lenalidomide outweighed the increased risk of SPMs in both TE-and TI-MM patients.