Lenalidomide and second malignancies in myeloma patients

摘要

Survival of patients with multiple myeloma has improved dramatically since the introduction of stem-cell transplantation and new agents such as immunomodulatory drugs (thalidomide, lenalidomide, pomalidomide) and proteasome inhibitors (bortezomib, carfilzomib).1 Lenalidomide is well tolerated as an oral agent, and is a highly effective treatment for myeloma, with many trials exploring its use as a maintenance therapy. Several studies have confirmed that lenalidomide treatment improves progression-free survival in this setting, but the effects on overall survival, and the ideal duration of maintenance therapy, are not clear.2"4 The risk of developing second primary malignancies was previously shown to be greater in patients with multiple myeloma than in the general population; recently, this greater risk has also been shown for patients with the precursor state (monoclonal gammopathy of undetermined significance).5'6 This risk was increased with prolonged exposure to the alkylating agent melphalan, and was mainly caused by an increase in treatment-related myelodysplasia and acute myeloid leukaemia.56 Results of three studies showed that lenalidomide maintenance after autologous stem-cell transplantation was associated with an increase in second primary malignancies, but the exact effect of lenalidomide on second primary malignancies in patients with multiple myeloma has remained unclear.